CompletedPhase 2Results posted

Brain Imaging Study Of Rosiglitazone Efficacy And Safety In Alzheimer's Disease

Effects of Avandia on Cognition and Cerebral Glucose Utilisation in Subjects With Mild to Moderate Alzheimer's Disease (AD).

Lead sponsor

GlaxoSmithKline

Asset

Rosiglitazone

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•MMSE 16-26•Study partner/caregiver required

Primary endpoint

•Change From Baseline (Day 1) in Global

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2005-005089-34

Org study IDBRL-49653/461

NCT IDNCT00265148

Timeline

Milestones

Study start2004-05-18actual

Study first posted2005-12-14estimated

Primary completion2008-07-10actual

Study completion2008-07-10actual

Last update posted2020-11-18actual

Results first posted2020-11-18actual

Assets

Drug assets

Rosiglitazone

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Is male, or if female meets one or more of the following criteria:

•Post-menopausal females defined as menopause is defined as>6months without menstrual period with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However if indicated this should be confirmed by oestradiol and FSH levels consistent with menopause (according to local laboratory ranges). Women who are on HRT treatment, and have not been confirmed as post-menopausal should be advised to use contraception.(See Appendix 4)Pre-menopausal females with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.

•Meets the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for Alzheimer's disease, regardless of date of diagnosis relative to study entry date. (See Appendix 5) Has an Alzheimer's disease status of mild to moderate, as classified by a Mini Mental State Examination (MMSE) score of 16-26 inclusive at screening.

Is aged >/= 50 to </= 85 years Prior and current use of medication corresponds with criteria listed in Appendix 3.

•Has the ability to comply with requirements of cognitive and other testing.

•Has a permanent caregiver who is willing to attend all visits, oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status. (Subjects living alone or in a nursing home are not eligible).

•Has provided full written informed consent prior to the performance of any protocol-specified procedure; or if unable to provide informed consent due to cognitive status, provision of informed consent by cognitively intact legally acceptable representative (Where this is in accordance with local laws, regulations and ethics committee policy.) Caregiver has provided full written informed consent prior to the performance of any protocol-specified procedure

Exclusion criteria

•Is unsuitable for MRI scanning as assessed by local pre-MRI questionnaire (GSK to review.)

•Has a history of or suffers from claustrophobia.

•Is unable to lie comfortably on a bed inside a PET camera with their head in the field of view for at least 60 minutes as assessed by physical examination and medical history (e.g. back pain, arthritis).

•Has a history or presence of other neurological or other medical conditions that may influence the outcome or analysis of the PET scan results. Examples of such conditions include, but are not limited to stroke, traumatic brain injury, epilepsy or space occupying lesions.

•History of Type I or Type II diabetes mellitus.

•Fasting plasma glucose level>126mg/dL (>7.0mmol/L) or HbA1c>6.2%.

•History or clinical/laboratory evidence of moderate congestive heart failure defined by the New York Heart Association criteria (class I-IV)(See Appendix 6).

Ejection fraction</=40% determined by echocardiogram, or any other abnormality on echocardiography which in the view of the investigator required further investigation or intervention, or significant abnormalities on screening ECG (in accordance with the definitions below). Significant ECG abnormalities for the purposes of this study. Detection of any of the following abnormalities renders the subject ineligible for the study: 1. ECG heart rate <50 and >100 bpm 2. Any previously unrecognised sustained or paroxysmal arrhythmia requiring further intervention e.g. anticoagulation, cardioversion, anti-arrhythmic agent, further investigation etc. 3. PR interval >0.3 s, 2nd or 3rd degree heart block, symptomatic bifascicular block, trifascicular block. 4. Multifocal ventricular ectopy. 5. Ventricular bigemini or couplets, triplets etc. ECG abnormalities permitted at entry to this study. A subject will not be rendered ineligible by the presence of any of the following abnormalities: 1. AF with a heart rate <=90 in subjects receiving appropriate anti-platelet or anticoagulant therapy. 2. 1st degree heart block (PR<=0.3 s). 3. Subjects with a paced rhythm (further information required if subject has an implantable Cardiac Defibrillator). 4. Atrial ectopic beats. 5. Unifocal ventricular ectopic beats. 6. Left or right bundle branch block. 7. Asymptomatice bifascicular block. 8. Left ventricular hypertrophy. 9. Q waves present suggesting previous MI. 10. Repolarisation abnormalities History of new cardiovascular event within the last 6 months (i.e. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome [non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina) or significant arrhythmia; or major intervention (e.g. cardiac surgery or angiography plus stenting) scheduled.

•History or clinical laboratory evidence of cerebrovascular disease (stroke, transient ischaemic attack, haemorrhage), or diagnosis of possible, probable or definite vascular dementia in accordance with National Institute of Neurological Disorders and Stroke, and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria (See Appendix 8).

•History or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. structural abnormality, epilepsy, infectious or inflammatory/demyelinating CNS conditions, Parkinson's disease.

Significant peripheral oedema at the time of screening as assessed by Clinical Evaluation of Oedema and/or Signs of Congestive Heart Failure (Appendix 14)

•History of major psychiatric illness such as schizophrenia or bipolar affective disorder, or current depression (score on Hospital Anxiety and Depression Scale (HADS) depression questions >7, See Appendix 9).

Systolic blood pressure >165 mmHg or diastolic blood pressure >95 mmHG whilst receiving optimal antihypertensive therapy according to local practice.

Clinically significant anaemia (i.e.haemoglobin <11g/dL for males or <10 g/dL for females) or presence of haemoglobinopathies which would prevent accurate assessment of HbA1c.

Renal dysfunction, defined as creatinine clearance <30 ml/min (calculated from serum creatinine using the Cockcroft-Gault formula, See Appendix 10).

ALT, AST, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of normal laboratory range, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis (Childs-Pugh classes B/C)) without enzyme elevation.

•Fasting triglycerides >12mmol/L Abnormal/positive result within the past 12 months or at screening for any of the following tests: vitamin B12 (</=200pg/mL), syphilis serology, thyroid stimulating hormone.

•History or presence of gastro-intestinal, hepatic or renal disease or other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.

any clinically relevant abnormality, medical or psychiatric condition, which, in the opinion of the investigator, makes the subject unsuitable for inclusion in the study.

•Has donated >/= ml of blood within the past 2 months. Use of any other investigational agent within 30 days or 5 half-lives (whichever is longer) prior to the screening visit.

History of alcohol abuse, or of drug abuse within the past 6 months (or has tested positive for drugs of abuse at screening).

Subject is unable (with assistance, if appropriate) to take study medication as prescribed throughout the study.

•History of non-compliance with prescribed medication, or risk of non-compliance with study medication or procedures.

Subject is an immediate family member or employee of the participating investigator or of any of the participating site staff.

Shows any neurological abnormality by MRI, which in the opinion of the Principal Investigator would introduce additional risk factors, study procedures or effect endpoint data. MRI scanning will only be conducted on subjects who satisfy all other eligibility criteria.

•History of bone marrow transplant Exhibits screening/baseline results not consistent with AD e.g. radiological findings, or results on cognitive tests.

Use of tacrine within 30 days prior to the screening visit.

Endpoints (54)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Memory

Global cognition

Neuroimaging

Safety / tolerability / PK

Other clinical outcomes

Behavior / neuropsychiatric

Global cognition

4 endpoints

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS-COG) Total Score Over Period

Time frame:Baseline (Day 1), and Months 1, 6, and 12

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Mini-mental State Examination (MMSE) Score Over Period

Time frame:Baseline (Day 1), and up to Month 12

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS-COG) Total Score Over Period

Time frame:Baseline (Day 1), and Months 1, 6, and 12

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
PlaceboMonth 1n=39 Participants	-0.	5.38
Month 6n=34 Participants	1.7	6.73
Month 12n=31 Participants	5.7	7.52
RosiglitazoneMonth 1n=39 Participants	-0.5	4.84
Month 6n=35 Participants	3.2	5.58
Month 12n=31 Participants	6.6	7.80

Mean Difference (Net)-0.2095% CI-2.38 - 1.99p0.8593Repeated measure mixed model

At Month 1

Mean Difference (Net)1.4495% CI-1.43 - 4.32p0.3201Repeated measure mixed model

At Month 6

Mean Difference (Net)2.1895% CI-1.68 - 6.04p0.2627Repeated measure mixed model

At Month 12

Mean Difference (Net)1.1495% CI-1.35 - 3.64p0.3633Repeated measure mixed model

For overall period

Secondary/registry result

Change From Baseline in Mini-mental State Examination (MMSE) Score Over Period

Time frame:Baseline (Day 1), and up to Month 12

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
Placebon=30 Participants	-3.3	4.09
Rosiglitazonen=30 Participants	-2.6	3.27

Memory

6 endpoints

Secondary/protocol endpoint

Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test

Time frame:Baseline (Day 1), and Months 1, 6, and 12

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline (Day 1) in Delayed Free Recall Items Over Period by Stroop Colour Word Interference (SCWI) at Months 1, 6 and 12

Time frame:Baseline (Day 1), Months1, 6, and 12

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period

Time frame:Baseline (Day 1), Months 1, 6, and 12

change from baseline, improvement

Secondary/registry result

Change From Baseline (Day 1) in Delayed Free Recall Words at Months 1, 6, and 12 by Buschke Selective Reminding (BSR) Test

Time frame:Baseline (Day 1), and Months 1, 6, and 12

change from baseline, improvement

Posted result

Group	Value (mean), Number of words recalled	Standard deviation
PlaceboDelayed free recall, Month 1n=32 Participants	0.1	1.72
Delayed free recall, Month 6n=27 Participants	-0.1	1.56
Delayed free recall, Month 12n=25 Participants	-0.4	1.32
Trial 1 immediate, Month 1n=32 Participants	0.2	1.30
Trial 1 immediate, Month 6n=27 Participants	-0.2	1.69
Trial 1 immediate, Month 12n=25 Participants	-0.6	1.32
Trial 8 immediate, Month 1n=32 Participants	-0.2	1.82
Trial 8 immediate, Month 6n=27 Participants	-0.3	1.29
Trial 8 immediate, Month 12n=25 Participants	-0.9	1.32
For all 8 immediate trial, Month 1n=32 Participants	-1.4	7.27
For all 8 immediate trial, Month 6n=27 Participants	-3.0	7.31
For all 8 immediate trial, Month 12n=25 Participants	-5.8	7.95
Uncued words recalled, Month 1n=32 Participants	-1.7	8.56
Uncued words recalled, Month 6n=27 Participants	-3.2	7.92
Uncued words recalled, Month 12n=25 Participants	-7.0	9.91
RosiglitazoneDelayed free recall, Month 1n=34 Participants	0.2	1.23
Delayed free recall, Month 6n=31 Participants	0.0	1.21
Delayed free recall, Month 12n=26 Participants	-0.4	1.53
Trial 1 immediate, Month 1n=34 Participants	-0.1	1.13
Trial 1 immediate, Month 6n=31 Participants	-0.1	1.42
Trial 1 immediate, Month 12n=26 Participants	-0.5	1.27
Trial 8 immediate, Month 1n=34 Participants	0.0	1.45
Trial 8 immediate, Month 6n=31 Participants	-0.2	1.21
Trial 8 immediate, Month 12n=26 Participants	-0.2	1.03
For all 8 immediate trial, Month 1n=34 Participants	0.9	5.51
For all 8 immediate trial, Month 6n=31 Participants	0.4	5.85
For all 8 immediate trial, Month 12n=26 Participants	-0.9	5.27
Uncued words recalled, Month 1n=34 Participants	0.9	5.43
Uncued words recalled, Month 6n=31 Participants	0.9	7.55
Uncued words recalled, Month 12n=26 Participants	-2.0	8.59

Mean Difference (Net)0.1195% CI-0.59 - 0.80p0.7618Repeated measure mixed model

For BSR test , Month 1

Mean Difference (Net)0.0695% CI-0.53 - 0.66p0.8350Repeated measure mixed model

For BSR test, Month 6

Mean Difference (Net)-0.1495% CI-0.78 - 0.51p0.6735Repeated measure mixed model

For BSR test, Month 12

Secondary/registry result

Change From Baseline (Day 1) in Delayed Free Recall Items Over Period by Stroop Colour Word Interference (SCWI) at Months 1, 6 and 12

Time frame:Baseline (Day 1), Months1, 6, and 12

change from baseline, improvement

Posted result

Group	Value (mean), Milliseconds	Standard deviation
PlaceboMonth 1n=38 Participants	-0.0	0.88
Month 6n=33 Participants	0.1	0.97
Month 12n=29 Participants	0.5	1.09
RosiglitazoneMonth 1n=39 Participants	-0.4	1.33
Month 6n=35 Participants	-0.2	1.06
Month 12n=30 Participants	-0.3	1.78

Mean Difference (Net)-0.0795% CI-0.44 - 0.30p0.7045Repetaed measure mixed model

For Month 1

Mean Difference (Net)-0.0495% CI-0.40 - 0.32p0.8181Repeated measure mixed model

For Month 6

Mean Difference (Net)-0.0995% CI-0.71 - 0.53p0.7688Repeated measure mixed model

AT Month 12

Mean Difference (Net)-0.0795% CI-0.40 - 0.26p0.6810Repeated measure mixed model

Overall

Secondary/registry result

Change From Baseline (Day 1) in Simplified Spatial Paired Associate Learning (SSPAL) Response Over Period

Time frame:Baseline (Day 1), Months 1, 6, and 12

change from baseline, improvement

Posted result

Group	Value (mean), Proportion of accurate responses	Standard deviation
PlaceboGlobal accuracy, Month 1n=29 Participants	-0.0	0.16
Global accuracy, Month 6n=25 Participants	-0.0	0.14
Global accuracy, Month 12n=21 Participants	-0.0	0.15
New accuracy, Month 1n=29 Participants	0.1	0.22
New accuracy, Month 6n=25 Participants	0.0	0.19
New accuracy, Month 12n=21 Participants	-0.0	0.22
RosiglitazoneGlobal accuracy, Month 1n=25 Participants	0.0	0.06
Global accuracy, Month 6n=24 Participants	-0.0	0.12
Global accuracy, Month 12n=21 Participants	0.0	0.12
New accuracy, Month 1n=25 Participants	0.0	0.17
New accuracy, Month 6n=24 Participants	-0.0	0.29
New accuracy, Month 12n=21 Participants	-0.1	0.22

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Change From Baseline in Neuropsychiatric Inventory Score Over Period

Time frame:Baseline (Day 1), Months 1, 6 and 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Neuropsychiatric Inventory Score Over Period

Time frame:Baseline (Day 1), Months 1, 6 and 12

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
PlaceboMonth 1n=31 Participants	-1.6	6.30
Month 6n=28 Participants	2.1	8.63
Month 12n=25 Participants	0.9	8.39
RosiglitazoneMonth 1n=32 Participants	-2.6	6.82
Month 6n=30 Participants	-0.8	11.59
Month 12n=27 Participants	1.8	13.84

Neuroimaging

4 endpoints

Secondary/protocol endpoint

Change From Baseline in Normalized Brain Volume Over Period

Time frame:Baseline (Day 1), Month 6 and Month 12

change from baseline, improvement

Secondary/protocol endpoint

Percent Change From Baseline in Brain Volume Over Period

Time frame:Baseline (Day 1), Month 6, and Month 12

percent change from baseline, improvement

Secondary/registry result

Change From Baseline in Normalized Brain Volume Over Period

Time frame:Baseline (Day 1), Month 6 and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), Cubic millimeter	Standard deviation
PlaceboMonth 6n=28 Participants	-4553.1	43069.12
Month 12n=27 Participants	-16599.9	47173.85
RosiglitazoneMonth 6n=33 Participants	-15995.6	41075.95
Month 12n=29 Participants	-13929.6	31031.06

Mean Difference (Net)-4971.695% CI-255515.6 - 15572.4p0.6299Repeated measure mixed model

At Month 6

Mean Difference (Net)12223.095% CI-7450.6 - 31896.5p0.2184Repeated measure mixed model

At Month 12

Secondary/registry result

Percent Change From Baseline in Brain Volume Over Period

Time frame:Baseline (Day 1), Month 6, and Month 12

percent change from baseline, improvement

Posted result

Group	Value (mean), Percent change	Standard deviation
PlaceboMonth 6n=21 Participants	-0.9	0.62
Month 12n=19 Participants	-2.4	1.40
RosiglitazoneMonth 6n=28 Participants	-1.4	0.94
Month 12n=28 Participants	-2.6	1.48

Mean Difference (Net)-0.695% CI-1.0 - -0.1p0.0129Repeated measure mixed model

For Month 6

Mean Difference (Net)-0.295% CI-1.0 - 0.6p0.5607Repeated measure mixed model

For Month 12

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame:Up to 12 months

change from baseline, event

Secondary/protocol endpoint

Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Parameters at Screening and Follow-up

Time frame:At screening (within 1 month of Day 1) and follow-up period (within 2 weeks of final dose [12 months])

event count, event

Secondary/registry result

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame:Up to 12 months

change from baseline, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboAny AEn=40 Participants	32	-
Any SAEn=40 Participants	6	-
RosiglitazoneAny AEn=40 Participants	33	-
Any SAEn=40 Participants	4	-

Secondary/registry result

Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Parameters at Screening and Follow-up

Time frame:At screening (within 1 month of Day 1) and follow-up period (within 2 weeks of final dose [12 months])

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboAt screeningn=40 Participants	18	-
At follow-upn=40 Participants	5	-
RosiglitazoneAt screeningn=40 Participants	18	-
At follow-upn=40 Participants	10	-

Other clinical outcomes

4 endpoints

Secondary/protocol endpoint

Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Outside the Concern Range at Month 12

Time frame:At Month 12

event count, event

Secondary/protocol endpoint

Number of Participants With Body Weight and Height Outside the Clinical Concern at Month 12

Time frame:At Month 12

change from baseline, improvement

Secondary/registry result

Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Outside the Concern Range at Month 12

Time frame:At Month 12

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboSBP, >140 or <90n=39 Participants	20	-
SBP, Increase from Baseline>=40n=39 Participants	1	-
SBP, Decrease from Baseline>=30n=39 Participants	12	-
DBP, >90 or <50n=39 Participants	5	-
DBP, Increase from Baseline>=30n=39 Participants	1	-
DBP, Decrease from Baseline>=20n=39 Participants	3	-
RosiglitazoneSBP, >140 or <90n=40 Participants	23	-
SBP, Increase from Baseline>=40n=40 Participants	3	-
SBP, Decrease from Baseline>=30n=40 Participants	13	-
DBP, >90 or <50n=40 Participants	2	-
DBP, Increase from Baseline>=30n=40 Participants	1	-
DBP, Decrease from Baseline>=20n=40 Participants	7	-

Secondary/registry result

Number of Participants With Body Weight and Height Outside the Clinical Concern at Month 12

Time frame:At Month 12

change from baseline, improvement

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboIncrease from Baseline >=7%n=33 Participants	2	-
Decrease from Baseline >=7%n=33 Participants	2	-
RosiglitazoneIncrease from Baseline >=7%n=31 Participants	5	-
Decrease from Baseline >=7%n=31 Participants	2	-

Other (unclassified)

30 endpoints

Primary/protocol endpoint/low confidence

Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Primary/registry result/low confidence

Change From Baseline (Day 1) in Global and Regional Indices of Cerebral Metabolic Rate of Glucose (CMRglu) at Month 12

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), Milligrams per cubic centimeter(mg/cm^3)	Standard deviation
PlaceboGrey mattern=25 Participants	-0.2793	0.48541
Posterior cingulate gyrusn=25 Participants	-0.3143	0.57567
Frontal loben=25 Participants	-0.3087	0.55631
Parietal loben=25 Participants	-0.3081	0.50596
Posterior temporal loben=25 Participants	-0.2771	0.40458
Cerebellumn=22 Participants	-0.2523	0.46730
Medial temporal loben=25 Participants	-0.1950	0.33360
RosiglitazoneGrey mattern=27 Participants	-0.0887	0.34985
Posterior cingulate gyrusn=27 Participants	-0.0786	0.36019
Frontal loben=27 Participants	-0.1131	0.36876
Parietal loben=27 Participants	-0.1175	0.33335
Posterior temporal loben=27 Participants	-0.1122	0.32346
Cerebellumn=25 Participants	-0.0248	0.38874
Medial temporal loben=27 Participants	-0.0349	0.32429

Mean Difference (Net)0.133495% CI-0.0583 - 0.3251p0.1695Mixed model for repeated measures

For Grey matter

Mean Difference (Net)0.175095% CI-0.0380 - 0.3880p0.1057Mixed model for repeated measures

For posterior cingulate Gyrus

Mean Difference (Net)0.142695% CI-0.0691 - 0.3543p0.1833Mixed model for repeated measures

For Frontal lobe

Mean Difference (Net)0.136695% CI-0.0574 - 0.3307p0.1644Mixed model for repeated measures

For parietal lobe

Mean Difference (Net)0.125995% CI-0.0471 - 0.2989p0.1509Mixed model for repeated measures

For Posterior temporal lobe

Mean Difference (Net)0.133995% CI-0.0747 - 0.3424p0.2041Mixed model for repeated measures

For cerebellum

Mean Difference (Net)0.109495% CI-0.0385 - 0.2572p0.1445Mixed model for repeated measures

For medial temporal lobe

Secondary/protocol endpoint/low confidence

Change From Baseline (Day 1) in CMRGlu Indices at Months 1 and 6

Time frame:Baseline (Day 1), Months 1, and 6

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period

Time frame:Baseline (Day 1) and up to 12 months

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Cognitive Test by Simple Reaction Time (SRT) Method Over Period

Time frame:Baseline (Day 1) and up to 12 months

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Clinician Based Impression of Change-plus (CBIC +) Score Over Period

Time frame:Baseline (Day 1) and Months 1, 6, and 12

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Fasting Plasma Glucose at Month 12

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Secondary/registry result/low confidence

Change From Baseline (Day 1) in CMRGlu Indices at Months 1 and 6

Time frame:Baseline (Day 1), Months 1, and 6

change from baseline, improvement

Posted result

Group	Value (mean), mg/cm^3	Standard deviation
PlaceboMonth 1n=33 Participants	-0.1049	0.39301
Month 6n=30 Participants	-0.1556	0.36397
RosiglitazoneMonth 1n=37 Participants	0.0475	0.46904
Month 6n=33 Participants	-0.0269	0.35311

Mean Difference (Net)0.121195% CI-0.0763 - 0.3185p0.2251Mixed model for repeated measures

At Month 1

Mean Difference (Net)0.089395% CI-0.0643 - 0.2430p0.2497Mixed model for repeated measures

For Month 6

Secondary/protocol endpoint/low confidence

Change From Baseline in Glycosylated Hemoglobin [HbA1C] at Month 12

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Lipid (Cholesterol) and Apo-lipoprotein Levels at Month 12

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Inflammatory Biomarkers (CD40, C-reactive Protein [CRP] , Interleukin [ IL ]-6, and Tumor Necrosing Factor [TNF]-Alpha)

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Insulin Sensitivity Measured by Homeostasis Model Assessment of Insulin Resistance (HOMA IR)

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Secondary/registry result/low confidence

Change From Baseline (Day 1) in Accuracy by Choice Reaction Time (CRT) Test Over Period

Time frame:Baseline (Day 1) and up to 12 months

change from baseline, improvement

Posted result

Group	Value (mean), Percent accuracy	Standard deviation
PlaceboAccuracy, Left, Month 1n=33 Participants	-0.0	0.04
Accuracy, Left, Month 6n=30 Participants	-0.1	0.16
Accuracy, Left, Month 12n=28 Participants	-0.1	0.14
Accuracy, Right, Month 1n=33 Participants	0.0	0.02
Accuracy, Right, Month 6n=30 Participants	-0.0	0.02
Accuracy, Right, Month 12n=28 Participants	-0.0	0.13
RosiglitazoneAccuracy, Left, Month 1n=32 Participants	0.0	0.15
Accuracy, Left, Month 6n=30 Participants	0.0	0.14
Accuracy, Left, Month 12n=25 Participants	0.0	0.12
Accuracy, Right, Month 1n=32 Participants	0.0	0.15
Accuracy, Right, Month 6n=30 Participants	0.0	0.15
Accuracy, Right, Month 12n=25 Participants	0.0	0.14

Secondary/protocol endpoint/low confidence

Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype

Time frame:Up to 12 months

event count, event

Secondary/registry result/low confidence

Change From Baseline in Cognitive Test by Simple Reaction Time (SRT) Method Over Period

Time frame:Baseline (Day 1) and up to 12 months

change from baseline, improvement

Posted result

Group	Value (mean), Milliseconds	Standard deviation
PlaceboMonth 1n=33 Participants	-17.1	161.70
Month 6n=31 Participants	37.8	170.67
Month 12n=29 Participants	177.7	359.91
RosiglitazoneMonth 1n=32 Participants	36.5	162.72
Month 6n=32 Participants	59.3	158.32
Month 12n=27 Participants	76.4	179.78

Secondary/registry result/low confidence

Change From Baseline in Clinician Based Impression of Change-plus (CBIC +) Score Over Period

Time frame:Baseline (Day 1) and Months 1, 6, and 12

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
PlaceboMonth 1n=36 Participants	3.9	1.08
Month 6n=34 Participants	4.7	0.93
Month 12n=31 Participants	4.9	1.03
RosiglitazoneMonth 1n=37 Participants	3.9	0.95
Month 6n=35 Participants	4.5	1.22
Month 12n=31 Participants	4.8	1.38

Mean Difference (Net)-0.1195% CI-0.48 - 0.26p0.5647Repetaed measure mixed model

For overall period

Mean Difference (Net)-0.0095% CI-0.46 - 0.46p0.9935Repeated measure mixed model

For Month 1

Mean Difference (Net)-0.2295% CI-0.72 - 0.28p0.3794Repeated measure mixed model

At Month 6

Mean Difference (Net)-0.1095% CI-0.70 - 0.49p0.7357Repeated measure mixed model

At Month 12

Secondary/protocol endpoint/low confidence

Number of Participants With Heart Rate/ Pulse Rate Outside the Concern Range at Month 12

Time frame:At Month 12

event count, event

Secondary/protocol endpoint/low confidence

Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month

Time frame:At Month 12

descriptive

Secondary/protocol endpoint/low confidence

Number of Participants With Hematological Data of Potential Clinical Concern (PCC) at End of Treatment (Month 12)

Time frame:At Month 12

event count, event

Secondary/registry result/low confidence

Change From Baseline in Fasting Plasma Glucose at Month 12

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), Millimoles per Liter	Standard deviation
Placebon=27 Participants	0.2556	0.99974
Rosiglitazonen=28 Participants	-0.1750	0.48810

Secondary/protocol endpoint/low confidence

Number of Participants With Clinical Chemistry Data of PCC at End of the Treatment (Month 12)

Time frame:At Month 12

event count, event

Secondary/registry result/low confidence

Change From Baseline in Glycosylated Hemoglobin [HbA1C] at Month 12

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), Percentage of HbA1c	Standard deviation
Placebon=32 Participants	0.0625	0.43533
Rosiglitazonen=31 Participants	0.3871	0.49514

Secondary/registry result/low confidence

Change From Baseline in Lipid (Cholesterol) and Apo-lipoprotein Levels at Month 12

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), Grams per Liter	Standard deviation
PlaceboApolipoprotein An=32 Participants	-0.0478	0.29284
Apolipoprotein Bn=32 Participants	-0.0191	0.18714
Cholesteroln=32 Participants	-0.2556	0.69756
RosiglitazoneApolipoprotein An=31 Participants	-0.2058	0.27424
Apolipoprotein Bn=31 Participants	-0.0006	0.25070
Cholesteroln=30 Participants	0.1340	1.09229

Secondary/registry result/low confidence

Change From Baseline in Inflammatory Biomarkers (CD40, C-reactive Protein [CRP] , Interleukin [ IL ]-6, and Tumor Necrosing Factor [TNF]-Alpha)

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), Nanograms per Liter	Standard deviation
PlaceboCD40n=31 Participants	-236.79	2500.30
CRPn=31 Participants	0.8161	5.94099
IL-6n=31 Participants	6.3390	22.5103
TNF-alphan=28 Participants	16.7893	53.0817
RosiglitazoneCD40n=30 Participants	130.543	2580.16
CRPn=30 Participants	-1.4800	4.63565
IL-6n=30 Participants	2.6370	11.1159
TNF-alphan=27 Participants	3.8407	15.9970

Secondary/registry result/low confidence

Change From Baseline in Insulin Sensitivity Measured by Homeostasis Model Assessment of Insulin Resistance (HOMA IR)

Time frame:Baseline (Day 1) and Month 12

change from baseline, improvement

Posted result

Group	Value (mean), HOMA IR score	Standard deviation
Placebon=31 Participants	-0.2703	12.6037
Rosiglitazonen=31 Participants	-5.9910	9.79511

Secondary/registry result/low confidence

Number of Participants by Apo-lipoprotein -e (APOE Epsilon)-4 Allele Subtype

Time frame:Up to 12 months

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboWith APOE4 genen=30 Participants	24	-
Without APOE4 genen=30 Participants	6	-
With E4E4 allelen=30 Participants	7	-
With E3E4 allelen=30 Participants	17	-
With E2E4 allelen=30 Participants	0	-
With E3E3 allelen=30 Participants	5	-
With E2E3 allelen=30 Participants	1	-
With E2E2 allelen=30 Participants	0	-
2 copies of APOE4 genen=30 Participants	7	-
1 copies of APOE4 genen=30 Participants	17	-
0 copies of APOE4 genen=30 Participants	6	-
RosiglitazoneWith APOE4 genen=29 Participants	15	-
Without APOE4 genen=29 Participants	14	-
With E4E4 allelen=29 Participants	6	-
With E3E4 allelen=29 Participants	8	-
With E2E4 allelen=29 Participants	1	-
With E3E3 allelen=29 Participants	12	-
With E2E3 allelen=29 Participants	1	-
With E2E2 allelen=29 Participants	1	-
2 copies of APOE4 genen=29 Participants	6	-
1 copies of APOE4 genen=29 Participants	9	-
0 copies of APOE4 genen=29 Participants	14	-

Secondary/registry result/low confidence

Number of Participants With Heart Rate/ Pulse Rate Outside the Concern Range at Month 12

Time frame:At Month 12

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboHeart rate >100 or <50n=39 Participants	4	-
Increase in heart rate from Baseline of >=30n=39 Participants	2	-
Dncrease in heart rate from Baseline of >=30n=39 Participants	0	-
RosiglitazoneHeart rate >100 or <50n=40 Participants	3	-
Increase in heart rate from Baseline of >=30n=40 Participants	4	-
Dncrease in heart rate from Baseline of >=30n=40 Participants	0	-

Secondary/registry result/low confidence

Global and Regional CMRglu Index by APOE Epsilon-4 Allele Subtype at 12 Month

Time frame:At Month 12

descriptive

Posted result

Group	Value (mean), milligrams per cubic centimeter	Standard deviation
PlaceboGrey matter, APOE positiven=16 Participants	-0.2649	0.58442
Posterior cingulate gyrus, APOE positiven=16 Participants	-0.2728	0.69449
Frontal lobe, APOE positiven=16 Participants	-0.2939	0.66878
Parietal lobe, APOE positiven=16 Participants	-0.2919	0.60832
Posterior temporal lobe, APOE positiven=16 Participants	-0.2722	0.48425
Cerebellum, APOE positiven=15 Participants	-0.2280	0.54477
Medial temporal lobe, APOE positiven=16 Participants	-0.1647	0.39800
Grey matter, APOE negativen=3 Participants	-0.1577	0.06551
Posterior cingulate gyrus, APOE negativen=3 Participants	-0.2655	0.11854
Frontal lobe, APOE negativen=3 Participants	-0.1967	0.09081
Parietal lobe, APOE negativen=3 Participants	-0.1549	0.08056
Posterior temporal lobe, APOE negativen=3 Participants	-0.1391	0.11660
Cerebellum, APOE negativen=3 Participants	-0.1732	0.05698
Medial temporal lobe, APOE negativen=3 Participants	-0.1134	0.06707
RosiglitazoneGrey matter, APOE positiven=11 Participants	-0.0903	0.44270
Posterior cingulate gyrus, APOE positiven=11 Participants	-0.0987	0.43553
Frontal lobe, APOE positiven=11 Participants	-0.1046	0.45385
Parietal lobe, APOE positiven=11 Participants	-0.1404	0.42635
Posterior temporal lobe, APOE positiven=11 Participants	-0.1175	0.42617
Cerebellum, APOE positiven=10 Participants	-0.0375	0.49150
Medial temporal lobe, APOE positiven=11 Participants	-0.0004	0.43929
Grey matter, APOE negativen=12 Participants	-0.0107	0.16654
Posterior cingulate gyrus, APOE negativen=12 Participants	0.0141	0.17927
Frontal lobe, APOE negativen=12 Participants	-0.0323	0.17438
Parietal lobe, APOE negativen=12 Participants	-0.0362	0.17425
Posterior temporal lobe, APOE negativen=12 Participants	-0.0443	0.16786
Cerebellum, APOE negativen=11 Participants	0.0742	0.15230
Medial temporal lobe, APOE negativen=12 Participants	0.0026	0.14382

Mean Difference (Net)0.115495% CI-0.0967 - 0.3275p0.2800Repeated measure mixed model

For Grey matter, APOE Epsilon-4 status positive

Mean Difference (Net)0.133795% CI-0.1931 - 0.4605p0.4159Repeated measure mixed model

For Grey matter, APOE Epsilon-4 status negative

Mean Difference (Net)0.149195% CI-0.0897 - 0.3878p0.2158Repeated measure mixed model

For posterior cingulate gyrus, APOE Epsilon-4 status positive

Mean Difference (Net)0.234695% CI-0.1350 - 0.6042p0.2087Repeated measure mixed model

For posterior cingulate gyrus, APOE Epsilon-4 status negative

Mean Difference (Net)0.123395% CI-0.1162 - 0.3628p0.3064Repeated measure mixed model

For Frontal lobe, APOE Epsilon-4 status positive

Mean Difference (Net)0.173495% CI-0.1952 - 0.5420p0.3500Repeated measure mixed model

For Frontal lobe APOE Epsilon-4 status negative

Mean Difference (Net)0.130095% CI-0.0937 - 0.3538p0.2487Repeated measure mixed model

For parietal lobe, APOE Epsilon-4 status positive

Mean Difference (Net)0.103895% CI-0.2440 - 0.4516p0.5521Repeated measure mixed model

For parietal lobe, APOE Epsilon-4 status negative

Mean Difference (Net)0.138495% CI-0.0640 - 0.3409p0.1760Repeated measure mixed model

For posterior temporal lobe, APOE Epsilon-4 status positive

Mean Difference (Net)0.083795% CI-0.2303 - 0.3978p0.5952Repeated measure mixed model

For posterior temporal lobe, APOE Epsilon-4 status negative

Mean Difference (Net)0.084795% CI-0.1169 - 0.2863p0.4025Repeated measure mixed model

For Cerebellum, APOE Epsilon-4 status positive

Mean Difference (Net)0.153695% CI-0.1458 - 0.4530p0.3081Repeated measure mixed model95

For Cerebellum, APOE Epsilon-4 status negative

Mean Difference (Net)0.083995% CI-0.0758 - 0.2436p0.2964Repeated measure mixed model

For medial temporal lobe, APOE Epsilon-4 status positive

Mean Difference (Net)0.153695% CI-0.0892 - 0.3963p0.2101Repeated measure mixed model

For medial temporal lobe, APOE Epsilon-4 status negative

Secondary/registry result/low confidence

Number of Participants With Hematological Data of Potential Clinical Concern (PCC) at End of Treatment (Month 12)

Time frame:At Month 12

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboHemoglobin, Month 12, Ln=31 Participants	0	-
Neutrophils, Month 12, Ln=31 Participants	0	-
Platelets, Month 12, Ln=30 Participants	0	-
White cells, Month 12, Ln=31 Participants	1	-
Lymphoctes percentage, Month 12, Ln=33 Participants	1	-
RosiglitazoneHemoglobin, Month 12, Ln=29 Participants	1	-
Neutrophils, Month 12, Ln=29 Participants	1	-
Platelets, Month 12, Ln=28 Participants	1	-
White cells, Month 12, Ln=29 Participants	1	-
Lymphoctes percentage, Month 12, Ln=31 Participants	0	-

Secondary/registry result/low confidence

Number of Participants With Clinical Chemistry Data of PCC at End of the Treatment (Month 12)

Time frame:At Month 12

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
PlaceboDirect bilirubin, Hn=34 Participants	1	-
Cholesterol, Hn=34 Participants	1	-
Glucose, Hn=32 Participants	1	-
Low density lipoprotein cholesterol, Hn=34 Participants	2	-
RosiglitazoneDirect bilirubin, Hn=31 Participants	0	-
Cholesterol, Hn=31 Participants	0	-
Glucose, Hn=31 Participants	0	-
Low density lipoprotein cholesterol, Hn=31 Participants	5	-

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Tzimopoulou S, Cunningham VJ, Nichols TE, Searle G, Bird NP, Mistry P, Dixon IJ, Hallett WA, Whitcher B, Brown AP, Zvartau-Hind M, Lotay N, Lai RY, Castiglia M, Jeter B, Matthews JC, Chen K, Bandy D, Reiman EM, Gold M, Rabiner EA, Matthews PM. A multi-center randomized proof-of-concept clinical trial applying [(1)(8)F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer's disease. J Alzheimers Dis. 2010;22(4):1241-56. doi: 10.3233/JAD-2010-100939.
PMID20930300via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.