TerminatedPhase NAResults posted

Acute Effects Of Donepezil On Brain Perfusion And Memory In Subjects With Cognitive Impairment And Mild Alzheimer's Disease

A Methodology Study To Evaluate The Acute Effects Of Donepezil On Regional Cerebral Perfusion And Cognition In Subjects With Amnestic MCI And Mild Alzheimer's Disease

Lead sponsor

Pfizer

Asset

Donepezil

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•Alzheimer's disease•APP mutation required•MMSE 21-30

Primary endpoints

•Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1•Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8•Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8

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

Org study IDA9001437

NCT IDNCT01082965

Timeline

Milestones

Study first posted2010-03-09estimated

Study start2010-07 (month precision)

Primary completion2012-07actual (month precision)

Study completion2012-07actual (month precision)

Last update posted2013-09-12estimated

Results first posted2013-09-12estimated

Assets

Drug assets

Donepezil

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age50 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Subjects and caregivers must provide written Informed Consent and be willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

•AD: Diagnostic evidence of probable AD consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria met by the site Physician at the time of the Screening visit. This evidence must be fully documented in the participant's file prior to the Baseline Visit.

•For amnestic Mild Cognitive Impairment (MCI): A Clinical Dementia Rating (CDR) of 0.5 (with memory box score of at least 0.5) and a memory complaint that is objectively verified using a test of episodic memory: Delayed recall from one paragraph of the Wechsler Logical Memory scale (cutoff scores by education - maximum score of 25).

•Less than or equal to 8 for 16 or more years of education; Less than or equal to 4 for 8-15 years of education; Less than or equal to 2 for 0-7 years of education.

•Mini Mental State Exam (MMSE) score of 21-30

•Male and female subjects of non child-bearing potential (or using appropriate birth control measures) who are at least 50 years of age.

•In generally good health, in the opinion of the Principal Investigator (PI), based on medical history, Body Mass Index (BMI), physical examination, vital signs, 12-lead ECG, and laboratory values, including hematology and chemistry values.

•No known genetic AD causes for early onset memory impairment (e.g., presenilin mutation), participants from a family with known autosomal dominant AD associated with mutations in APP, PS1, or PS2 genes or strongly suspected, but not yet identified mutations in APP, PS1 or PS2 genes or Down's syndrome are not eligible to enroll. Individuals from families with late onset AD with 2 or more affected family members may participate.

Type II diabetic subjects may be included provided that their disease and serum glucose values are controlled and being actively managed, as assessed by the PI using a fasting blood sugar and/or HgbA1C (per the PI's medical judgment in consultation with the Sponsor).

•Rosen-Modified Hachinski Ischemia Score less than or equal to 4

Exclusion criteria

•Diagnosis or history of other possible cause for or significant contributor to dementia, including but not limited to other neurodegenerative disorders (eg, frontotemporal dementia, Lewy body disease, vascular dementia), vitamin B12 deficiency (reflex Methylmalonic Acid (MMA) and folate if B12 is low), untreated thyroid disease, syphilis, alcoholism, severe or recurrent head injury that is clinically relevant to the disease under study, or onset of dementia following heart surgery or cardiac arrest.

•Diagnosis or history of cerebrovascular disease (eg, stroke, transient ischemic attack), severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage, or subdural hematoma that could contribute to the subject's current cognitive or functional status, impair ability to fully participate in the trial or that may impact status during the one week study.

•Specific exclusionary brain MRI findings identified prior to study or at baseline as determined by the investigator that could either contribute to the subject's current cognitive or functional decline impair ability to fully participate in the trial or that may impact status during the trial:

•History of cancer within the last year (except for cutaneous basal cell, squamous cell cancer resolved by excision, colon polyp resolved by excision, or non-progressive prostate cancer per investigator's judgment).

•History of clinically significant cardiovascular or renal events.

•Subjects with uncontrolled hypertension even with therapeutic intervention

•History of clinically significant (as determined by the PI in consultation with the Sponsor) syncope, seizure, head trauma, or clinically significant unexplained loss of consciousness within the last 5 years.

•A diagnosis of major depressive disorder or other psychiatric illness as the primary diagnosis per the DSM-IV text revision (TR) criteria per the investigator's judgment.

•History of schizophrenia, bipolar disorder, or other severe mental illness.

•Known history of alcohol or drug abuse (as defined by the DSM-IV-TR) within 5 years prior to dosing or a positive result regarding use of illicit drugs on the drug screening test.

•History of clinically significant symptoms of pulmonary disease that requires treatment (eg. asthma, COPD, or other chronic respiratory conditions).

•Known positive Human immunodeficiency virus (HIV) status.

•Unwilling or unable to comply with the Life Style guidelines described in this protocol.

Exclusions Related to Medications or Procedures

•Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) of Study Day 1.

•Use of tobacco- or nicotine-containing products within three months of study Day 1.

Use of medication(s) for cognitive enhancement ≤ 90 days before the first dose of study medication.

•Prescription: including but not limited to donepezil, galantamine, rivastigmine, tacrine, memantine, Axona™;

•Reason for stoppage of donepezil may not be related to tolerability issues or to gain entry in this study.

•Non-prescription treatments for cognitive enhancement.

-Subjects with either non-removable ferromagnetic implants (such as cardiac pacemaker), aneurysm clips or other foreign bodies that would contraindicate a brain MRI scan.

-A clinically significant (as determined by the PI) abnormality in the 12-lead ECG, including complete heart block, bradycardia (heart rate <40 beats/minute), sinus pauses >2 seconds, second or third degree heart block, QTc >450 or other abnormalities judged clinically significant by the PI.

Endpoints (14)

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

Neuroimaging

Memory

Executive function / language

Memory

4 endpoints

Secondary/protocol endpoint

Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8

Time frame:Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8

Time frame:Baseline, 5 hours post-dose on Day 8

change from baseline, improvement

Secondary/registry result

Change From Baseline in CogState Continuous Paired Associate Learning (CPAL) at Hour 5 on Day 1 and at Hour 1, 5 on Day 8

Time frame:Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8

change from baseline, improvement

Posted result

Group	Value (mean), errors	Standard deviation
DonepezilBaseline (n=9, 8)n=9 Participants	46.222	28.7436
Change at Hour 5 on Day 1 (n=9, 8)n=9 Participants	4.333	24.0936
Change at Hour 1 on Day 8 (n=9, 6)n=9 Participants	-5.444	31.9653
Change at Hour 5 on Day 8 (n=9, 6)n=9 Participants	2.000	16.3325
PlaceboBaseline (n=9, 8)n=8 Participants	37.625	17.8641
Change at Hour 5 on Day 1 (n=9, 8)n=8 Participants	-2.625	28.9084
Change at Hour 1 on Day 8 (n=9, 6)n=8 Participants	-15.833	15.8293
Change at Hour 5 on Day 8 (n=9, 6)n=8 Participants	-8.000	17.4126

LS Mean Difference5.0095% CI-21.82 - 31.82p0.6880Mixed Models Analysis

Change at Hour 5 on Day 1: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference9.7995% CI-11.30 - 30.87p0.3157Mixed Models Analysis

Change at Hour 0 on Day 8: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference9.8695% CI-13.56 - 33.28p0.3228Mixed Models Analysis

Change at Hour 5 on Day 8: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

Secondary/registry result

Change From Baseline in Rey Auditory Verbal Learning Test (RAVLT): Immediate and Delayed Recall at Hour 5 on Day 8

Time frame:Baseline, 5 hours post-dose on Day 8

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Standard deviation
DonepezilBaseline: Total IR (n=9, 8)n=9 Participants	25.667	7.3144
Baseline: Total DR (n=9, 8)n=9 Participants	2.444	2.3511
Change at Hour 5 on Day 8:Total IR (n=9, 6)n=9 Participants	3.333	4.1833
Change at Hour 5 on Day 8: Total DR (n=9, 6)n=9 Participants	0.444	1.9437
PlaceboBaseline: Total IR (n=9, 8)n=8 Participants	27.000	9.3960
Baseline: Total DR (n=9, 8)n=8 Participants	2.375	2.1998
Change at Hour 5 on Day 8:Total IR (n=9, 6)n=8 Participants	5.667	4.3665
Change at Hour 5 on Day 8: Total DR (n=9, 6)n=8 Participants	0.333	3.0111

LS Mean Difference-4.3995% CI-12.90 - 4.12p0.2540Mixed Models Analysis

Total IR: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.6095% CI-4.17 - 5.37p0.7684Mixed Models Analysis

Total DR: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

Executive function / language

2 endpoints

Secondary/protocol endpoint

Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8

Time frame:Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8

change from baseline, improvement

Secondary/registry result

Change From Baseline in CogState Test Battery at Hour 5 on Day 1 and at Hour 0, 5 on Day 8

Time frame:Baseline, 5 hours post-dose on Day 1; 1, 5 hours post-dose on Day 8

change from baseline, improvement

Posted result

Group	Value (mean), log10 milliseconds	Standard deviation
DonepezilBaseline: Detection Task (n=9, 8)n=9 Participants	2.572	0.1192
Baseline: Identification Task (n=9, 8)n=9 Participants	2.708	0.0635
Change at Hour 5 on Day 1: Detection Task (n=9, 8)n=9 Participants	0.002	0.0931
Change at Hour5 on Day1:Identification Task(n=9,8)n=9 Participants	0.020	0.0355
Change at Hour 0 on Day 8: Detection Task (n=9, 6)n=9 Participants	0.004	0.1184
Change at Hour0 on Day8:Identification Task(n=9,6)n=9 Participants	0.005	0.0630
Change at Hour 5 on Day 8: Detection Task (n=9, 6)n=9 Participants	-0.005	0.1001
Change at Hour5 on Day8:Identification Task(n=9,6)n=9 Participants	0.034	0.0782
PlaceboBaseline: Detection Task (n=9, 8)n=8 Participants	2.542	0.0953
Baseline: Identification Task (n=9, 8)n=8 Participants	2.727	0.0540
Change at Hour 5 on Day 1: Detection Task (n=9, 8)n=8 Participants	0.024	0.0706
Change at Hour5 on Day1:Identification Task(n=9,8)n=8 Participants	0.012	0.0371
Change at Hour 0 on Day 8: Detection Task (n=9, 6)n=8 Participants	-0.032	0.0512
Change at Hour0 on Day8:Identification Task(n=9,6)n=8 Participants	0.004	0.0493
Change at Hour 5 on Day 8: Detection Task (n=9, 6)n=8 Participants	0.004	0.0508
Change at Hour5 on Day8:Identification Task(n=9,6)n=8 Participants	0.004	0.0625

LS Mean Difference0.0495% CI-0.09 - 0.17p0.4940Mixed Models Analysis

Change at Hour 5 on Day 1, Detection Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.1095% CI-0.02 - 0.22p0.1031Mixed Models Analysis

Change at Hour 0 on Day 8, Detection Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0595% CI-0.06 - 0.16p0.3277Mixed Models Analysis

Change at Hour 5 on Day 8, Detection Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0195% CI-0.05 - 0.08p0.6585Mixed Models Analysis

Change at Hour 5 on Day 1, Identification Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0095% CI-0.07 - 0.08p0.8863Mixed Models Analysis

Change at Hour 0 on Day 8, Identification Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0495% CI-0.06 - 0.13p0.4388Mixed Models Analysis

Change at Hour 5 on Day 8, Identification Task: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

Neuroimaging

8 endpoints

Primary/protocol endpoint

Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1

Time frame:Baseline, 4 hours post-dose on Day 1

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8

Time frame:Baseline, 1 minute post-dose (Hour 0) on Day 8

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8

Time frame:Baseline, 4 hours post-dose on Day 8

change from baseline, improvement

Primary/registry result

Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 1

Time frame:Baseline, 4 hours post-dose on Day 1

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
DonepezilBaselinen=9 Participants	1.243	0.2586
Change at Hour 4 on Day 1n=9 Participants	0.156	0.5178
PlaceboBaselinen=6 Participants	1.564	0.2494
Change at Hour 4 on Day 1n=6 Participants	-0.017	0.3810

Leasts Square (LS) Mean-0.0195% CI-0.60 - 0.58p0.9742Mixed Models Analysis

Mixed model for repeated measures (MMRM) was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, Apolipoprotein E (ApoE) genotype, site as covariates.

Primary/registry result

Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 0 on Day 8

Time frame:Baseline, 1 minute post-dose (Hour 0) on Day 8

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Donepeziln=9 Participants	0.263	0.4872
Placebon=6 Participants	0.093	0.5624

LS Mean Difference-0.0195% CI-0.51 - 0.49p0.9638Mixed Models Analysis

MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

Primary/registry result

Change From Baseline in Posterior Cingulate Cortex Perfusion at Hour 4 on Day 8

Time frame:Baseline, 4 hours post-dose on Day 8

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Donepeziln=9 Participants	-0.008	0.2506
Placebon=6 Participants	-0.004	0.3948

LS Mean Difference-0.1995% CI-0.53 - 0.16p0.2548Mixed Models Analysis

MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

Secondary/protocol endpoint

Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8

Time frame:Baseline, 4 hours post-dose on Day 1, 1 minute post-dose (Hour 0), 4 hours post-dose on Day 8

change from baseline, improvement

Secondary/registry result

Change From Baseline in Arterial Spin Label (ASL) Perfusion at Hour 4 on Day 1 and at Hour 0, 4 on Day 8

Time frame:Baseline, 4 hours post-dose on Day 1, 1 minute post-dose (Hour 0), 4 hours post-dose on Day 8

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
DonepezilBaseline: Whole Brain Grayn=9 Participants	1.486	0.1215
Baseline: Superior Temporal Cortexn=9 Participants	1.749	0.2774
Baseline: Medial Temporal Cortexn=9 Participants	1.753	0.3186
Baseline: Inferior Temporal Cortexn=9 Participants	1.260	0.4634
Baseline: Medial Prefrontal Cortexn=9 Participants	1.488	0.1830
Baseline: Inferior Prefrontal Cortexn=9 Participants	1.381	0.2205
Baseline: Superior Prefrontal Cortexn=9 Participants	1.308	0.1236
Baseline: Inferior Parietal Cortexn=9 Participants	1.610	0.2824
Baseline: Insulan=9 Participants	1.390	0.1785
Baseline: Precuneusn=9 Participants	1.357	0.1904
Baseline: Anterior Cingulate Cortexn=9 Participants	1.236	0.2265
Baseline: Amygdalan=9 Participants	1.067	0.3025
Baseline: Thalamusn=9 Participants	1.417	0.4886
Baseline: Basal Ganglian=9 Participants	1.120	0.2781
Baseline: Hippocampusn=9 Participants	1.327	0.2726
Baseline: Landaun=9 Participants	1.916	0.3753
Change at Hour 4 on Day 1: Whole Brain Grayn=9 Participants	0.018	0.2309
Change at Hour 4 on Day 1:Superior Temporal Cortexn=9 Participants	0.031	0.3430
Change at Hour 4 on Day 1: Medial Temporal Cortexn=9 Participants	-0.066	0.5297
Change at Hour 4 on Day 1:Inferior Temporal Cortexn=9 Participants	-0.052	0.6289
Change at Hour 4 on Day 1:Medial Prefrontal Cortexn=9 Participants	0.035	0.2704
Change at Hour4 on Day1:Inferior Prefrontal Cortexn=9 Participants	0.143	0.1987
Change at Hour4 on Day1:Superior Prefrontal Cortexn=9 Participants	0.064	0.2702
Change at Hour 4 on Day 1:Inferior Parietal Cortexn=9 Participants	-0.054	0.2411
Change at Hour 4 on Day 1: Insulan=9 Participants	0.154	0.2813
Change at Hour 4 on Day 1: Precuneusn=9 Participants	-0.024	0.3002
Change at Hour 4 on Day1:Anterior Cingulate Cortexn=9 Participants	0.118	0.2168
Change at Hour 4 on Day 1: Amygdalan=9 Participants	0.187	0.5504
Change at Hour 4 on Day 1: Thalamusn=9 Participants	0.244	0.5697
Change at Hour 4 on Day 1: Basal Ganglian=9 Participants	0.292	0.4557
Change at Hour 4 on Day 1: Hippocampusn=9 Participants	0.128	0.2115
Change at Hour 4 on Day 1: Landaun=9 Participants	-0.051	0.3923
Change at Hour 0 on Day 8: Whole Brain Grayn=9 Participants	0.058	0.1024
Change at Hour 0 on Day 8:Superior Temporal Cortexn=9 Participants	0.051	0.2678
Change at Hour 0 on Day 8: Medial Temporal Cortexn=9 Participants	-0.015	0.3095
Change at Hour 0 on Day 8:Inferior Temporal Cortexn=9 Participants	0.084	0.6856
Change at Hour 0 on Day 8:Medial Prefrontal Cortexn=9 Participants	-0.198	0.4168
Change at Hour0 on Day8:Inferior Prefrontal Cortexn=9 Participants	0.043	0.3353
Change at Hour0 on Day8:Superior Prefrontal Cortexn=9 Participants	-0.152	0.3120
Change at Hour 0 on Day 8:Inferior Parietal Cortexn=9 Participants	0.005	0.5185
Change at Hour 0 on Day 8: Insulan=9 Participants	0.103	0.2679
Change at Hour 0 on Day 8: Precuneusn=9 Participants	0.055	0.4065
Change at Hour 0 on Day8:Anterior Cingulate Cortexn=9 Participants	0.279	0.4424
Change at Hour 0 on Day 8: Amygdalan=9 Participants	0.170	0.5388
Change at Hour 0 on Day 8: Thalamusn=9 Participants	0.195	0.6486
Change at Hour 0 on Day 8: Basal Ganglian=9 Participants	0.243	0.3925
Change at Hour 0 on Day 8: Hippocampusn=9 Participants	0.170	0.2832
Change at Hour 0 on Day 8: Landaun=9 Participants	-0.030	0.5354
Change at Hour 4 on Day 8: Whole Brain Grayn=9 Participants	0.010	0.1286
Change at Hour 4 on Day 8:Superior Temporal Cortexn=9 Participants	0.126	0.3065
Change at Hour 4 on Day 8: Medial Temporal Cortexn=9 Participants	-0.103	0.2852
Change at Hour 4 on Day 8:Inferior Temporal Cortexn=9 Participants	-0.194	0.5644
Change at Hour 4 on Day 8:Medial Prefrontal Cortexn=9 Participants	0.111	0.3606
Change at Hour4 on Day8:Inferior Prefrontal Cortexn=9 Participants	-0.031	0.2477
Change at Hour4 on Day8:Superior Prefrontal Cortexn=9 Participants	0.225	0.3460
Change at Hour 4 on Day 8:Inferior Parietal Cortexn=9 Participants	-0.175	0.4557
Change at Hour 4 on Day 8: Insulan=9 Participants	0.148	0.1477
Change at Hour 4 on Day 8: Precuneusn=9 Participants	-0.110	0.3846
Change at Hour 4 on Day8:Anterior Cingulate Cortexn=9 Participants	0.180	0.2939
Change at Hour 4 on Day 8: Amygdalan=9 Participants	0.097	0.4984
Change at Hour 4 on Day 8: Thalamusn=9 Participants	-0.124	0.5028
Change at Hour 4 on Day 8: Basal Ganglian=9 Participants	0.084	0.3393
Change at Hour 4 on Day 8: Hippocampusn=9 Participants	0.041	0.2770
Change at Hour 4 on Day 8: Landaun=9 Participants	-0.208	0.3152
PlaceboBaseline: Whole Brain Grayn=6 Participants	1.500	0.0869
Baseline: Superior Temporal Cortexn=6 Participants	1.773	0.1732
Baseline: Medial Temporal Cortexn=6 Participants	1.718	0.2778
Baseline: Inferior Temporal Cortexn=6 Participants	1.173	0.4024
Baseline: Medial Prefrontal Cortexn=6 Participants	1.709	0.1441
Baseline: Inferior Prefrontal Cortexn=6 Participants	1.486	0.1673
Baseline: Superior Prefrontal Cortexn=6 Participants	1.443	0.2046
Baseline: Inferior Parietal Cortexn=6 Participants	1.714	0.1628
Baseline: Insulan=6 Participants	1.533	0.2130
Baseline: Precuneusn=6 Participants	1.505	0.2781
Baseline: Anterior Cingulate Cortexn=6 Participants	1.442	0.1753
Baseline: Amygdalan=6 Participants	1.256	0.2966
Baseline: Thalamusn=6 Participants	1.468	0.3061
Baseline: Basal Ganglian=6 Participants	1.241	0.2461
Baseline: Hippocampusn=6 Participants	1.389	0.1229
Baseline: Landaun=6 Participants	2.025	0.0940
Change at Hour 4 on Day 1: Whole Brain Grayn=6 Participants	0.050	0.1010
Change at Hour 4 on Day 1:Superior Temporal Cortexn=6 Participants	0.023	0.3002
Change at Hour 4 on Day 1: Medial Temporal Cortexn=6 Participants	-0.006	0.2549
Change at Hour 4 on Day 1:Inferior Temporal Cortexn=6 Participants	0.090	0.2734
Change at Hour 4 on Day 1:Medial Prefrontal Cortexn=6 Participants	-0.164	0.2054
Change at Hour4 on Day1:Inferior Prefrontal Cortexn=6 Participants	-0.061	0.2299
Change at Hour4 on Day1:Superior Prefrontal Cortexn=6 Participants	-0.062	0.2361
Change at Hour 4 on Day 1:Inferior Parietal Cortexn=6 Participants	-0.016	0.1848
Change at Hour 4 on Day 1: Insulan=6 Participants	0.096	0.3276
Change at Hour 4 on Day 1: Precuneusn=6 Participants	0.053	0.2952
Change at Hour 4 on Day1:Anterior Cingulate Cortexn=6 Participants	0.173	0.2709
Change at Hour 4 on Day 1: Amygdalan=6 Participants	0.175	0.3785
Change at Hour 4 on Day 1: Thalamusn=6 Participants	-0.038	0.2209
Change at Hour 4 on Day 1: Basal Ganglian=6 Participants	0.014	0.1761
Change at Hour 4 on Day 1: Hippocampusn=6 Participants	0.036	0.2915
Change at Hour 4 on Day 1: Landaun=6 Participants	-0.033	0.1952
Change at Hour 0 on Day 8: Whole Brain Grayn=6 Participants	0.028	0.1569
Change at Hour 0 on Day 8:Superior Temporal Cortexn=6 Participants	0.038	0.3095
Change at Hour 0 on Day 8: Medial Temporal Cortexn=6 Participants	-0.052	0.2575
Change at Hour 0 on Day 8:Inferior Temporal Cortexn=6 Participants	-0.012	0.3842
Change at Hour 0 on Day 8:Medial Prefrontal Cortexn=6 Participants	-0.173	0.3050
Change at Hour0 on Day8:Inferior Prefrontal Cortexn=6 Participants	0.010	0.2188
Change at Hour0 on Day8:Superior Prefrontal Cortexn=6 Participants	-0.019	0.2863
Change at Hour 0 on Day 8:Inferior Parietal Cortexn=6 Participants	-0.106	0.2009
Change at Hour 0 on Day 8: Insulan=6 Participants	0.154	0.1816
Change at Hour 0 on Day 8: Precuneusn=6 Participants	0.059	0.3475
Change at Hour 0 on Day8:Anterior Cingulate Cortexn=6 Participants	0.167	0.3681
Change at Hour 0 on Day 8: Amygdalan=6 Participants	0.083	0.4233
Change at Hour 0 on Day 8: Thalamusn=6 Participants	-0.063	0.4992
Change at Hour 0 on Day 8: Basal Ganglian=6 Participants	0.040	0.3106
Change at Hour 0 on Day 8: Hippocampusn=6 Participants	0.047	0.2551
Change at Hour 0 on Day 8: Landaun=6 Participants	-0.105	0.2642
Change at Hour 4 on Day 8: Whole Brain Grayn=6 Participants	-0.022	0.0945
Change at Hour 4 on Day 8:Superior Temporal Cortexn=6 Participants	-0.037	0.1319
Change at Hour 4 on Day 8: Medial Temporal Cortexn=6 Participants	-0.110	0.2551
Change at Hour 4 on Day 8:Inferior Temporal Cortexn=6 Participants	-0.102	0.3114
Change at Hour 4 on Day 8:Medial Prefrontal Cortexn=6 Participants	-0.038	0.2262
Change at Hour4 on Day8:Inferior Prefrontal Cortexn=6 Participants	-0.001	0.2342
Change at Hour4 on Day8:Superior Prefrontal Cortexn=6 Participants	-0.007	0.1348
Change at Hour 4 on Day 8:Inferior Parietal Cortexn=6 Participants	-0.017	0.1560
Change at Hour 4 on Day 8: Insulan=6 Participants	0.078	0.2317
Change at Hour 4 on Day 8: Precuneusn=6 Participants	0.074	0.3035
Change at Hour 4 on Day8:Anterior Cingulate Cortexn=6 Participants	0.062	0.1423
Change at Hour 4 on Day 8: Amygdalan=6 Participants	0.019	0.3100
Change at Hour 4 on Day 8: Thalamusn=6 Participants	-0.077	0.5330
Change at Hour 4 on Day 8: Basal Ganglian=6 Participants	-0.066	0.2787
Change at Hour 4 on Day 8: Hippocampusn=6 Participants	0.017	0.1225
Change at Hour 4 on Day 8: Landaun=6 Participants	0.008	0.1418

LS Mean Difference-0.0395% CI-0.18 - 0.12p0.6316Mixed Models Analysis

Change at Hour 4 on Day 1, Whole Brain Gray: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0395% CI-0.12 - 0.19p0.6256Mixed Models Analysis

Change at Hour 0 on Day 8, Whole Brain Gray: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0395% CI-0.12 - 0.19p0.5847Mixed Models Analysis

Change at Hour 4 on Day 8, Whole Brain Gray: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1995% CI-0.46 - 0.09p0.1555Mixed Models Analysis

Change at Hour 4 on Day 1, Superior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1895% CI-0.51 - 0.14p0.2416Mixed Models Analysis

Change at Hour 0 on Day 8, Superior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0395% CI-0.33 - 0.26p0.8070Mixed Models Analysis

Change at Hour 4 on Day 8, Superior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0895% CI-0.59 - 0.43p0.6828Mixed Models Analysis

Change at Hour 4 on Day 1, Medial Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0195% CI-0.26 - 0.29p0.8987Mixed Models Analysis

Change at Hour 0 on Day 8, Medial Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0295% CI-0.28 - 0.25p0.8922Mixed Models Analysis

Change at Hour 4 on Day 8, Medial Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0795% CI-0.39 - 0.52p0.7555Mixed Models Analysis

Change at Hour 4 on Day 1, Inferior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.3095% CI-0.18 - 0.79p0.1928Mixed Models Analysis

Change at Hour 0 on Day 8, Inferior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.1295% CI-0.26 - 0.49p0.4946Mixed Models Analysis

Change at Hour 4 on Day 8, Inferior Temporal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0895% CI-0.56 - 0.40p0.7029Mixed Models Analysis

Change at Hour 4 on Day 1, Medial Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.3095% CI-0.68 - 0.08p0.1085Mixed Models Analysis

Change at Hour 0 on Day 8, Medial Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1395% CI-0.44 - 0.18p0.3588Mixed Models Analysis

Change at Hour 4 on Day 8, Medial Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.1795% CI-0.20 - 0.53p0.3053Mixed Models Analysis

Change at Hour 4 on Day 1, Inferior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0095% CI-0.36 - 0.36p0.9861Mixed Models Analysis

Change at Hour 0 on Day 8, Inferior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0795% CI-0.41 - 0.28p0.6558Mixed Models Analysis

Change at Hour 4 on Day 8, Inferior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0195% CI-0.53 - 0.51p0.9471Mixed Models Analysis

Change at Hour 4 on Day 1, Superior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.2795% CI-0.77 - 0.23p0.2136Mixed Models Analysis

Change at Hour 0 on Day 8, Superior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.1095% CI-0.47 - 0.67p0.6435Mixed Models Analysis

Change at Hour 4 on Day 8, Superior Prefrontal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.2095% CI-0.41 - 0.02p0.0659Mixed Models Analysis

Change at Hour 4 on Day 1, Inferior Parietal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0595% CI-0.41 - 0.31p0.7687Mixed Models Analysis

Change at Hour 0 on Day 8, Inferior Parietal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.3295% CI-0.73 - 0.10p0.1061Mixed Models Analysis

Change at Hour 4 on Day 8, Inferior Parietal Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1195% CI-0.41 - 0.19p0.3925Mixed Models Analysis

Change at Hour 4 on Day 1, Insula: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.2295% CI-0.58 - 0.14p0.1991Mixed Models Analysis

Change at Hour 0 on Day 8, Insula: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1095% CI-0.45 - 0.24p0.5176Mixed Models Analysis

Change at Hour 4 on Day 8, Insula: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1695% CI-0.50 - 0.18p0.3140Mixed Models Analysis

Change at Hour 4 on Day 1, Precuneus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0895% CI-0.46 - 0.29p0.6348Mixed Models Analysis

Change at Hour 0 on Day 8, Precuneus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.2695% CI-0.64 - 0.12p0.1491Mixed Models Analysis

Change at Hour 4 on Day 8, Precuneus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1695% CI-0.59 - 0.27p0.4226Mixed Models Analysis

Change at Hour 4 on Day 1, Anterior Cingulate Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0195% CI-0.49 - 0.50p0.9778Mixed Models Analysis

Change at Hour 0 on Day 8, Anterior Cingulate Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0195% CI-0.40 - 0.43p0.9456Mixed Models Analysis

Change at Hour 4 on Day 8, Anterior Cingulate Cortex: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.2095% CI-0.55 - 0.15p0.2299Mixed Models Analysis

Change at Hour 4 on Day 1, Amygdala: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1395% CI-0.54 - 0.28p0.5069Mixed Models Analysis

Change at Hour 0 on Day 8, Amygdala: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1495% CI-0.45 - 0.17p0.3524Mixed Models Analysis

Change at Hour 4 on Day 8, Amygdala: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.3495% CI-0.80 - 1.47p0.4182Mixed Models Analysis

Change at Hour 4 on Day 1, Thalamus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.3195% CI-0.42 - 1.04p0.3630Mixed Models Analysis

Change at Hour 0 on Day 8, Thalamus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0195% CI-0.73 - 0.74p0.9837Mixed Models Analysis

Change at Hour 4 on Day 8, Thalamus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.1995% CI-0.04 - 0.42p0.0974Mixed Models Analysis

Change at Hour 4 on Day 1, Basal Ganglia: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.1195% CI-0.04 - 0.27p0.1246Mixed Models Analysis

Change at Hour 0 on Day 8, Basal Ganglia: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference0.0695% CI-0.20 - 0.32p0.6190Mixed Models Analysis

Change at Hour 4 on Day 8, Basal Ganglia: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0795% CI-0.39 - 0.25p0.6350Mixed Models Analysis

Change at Hour 4 on Day 1, Hippocampus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0495% CI-0.40 - 0.32p0.8205Mixed Models Analysis

Change at Hour 0 on Day 8, Hippocampus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1595% CI-0.42 - 0.14p0.2959Mixed Models Analysis

Change at Hour 4 on Day 8, Hippocampus: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.1295% CI-0.56 - 0.32p0.5520Mixed Models Analysis

Change at Hour 4 on Day 1, Landau: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.0395% CI-0.50 - 0.45p0.9046Mixed Models Analysis

Change at Hour 0 on Day 8, Landau: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

LS Mean Difference-0.3295% CI-0.62 - -0.02p0.0402Mixed Models Analysis

Change at Hour 4 on Day 8, Landau: MMRM was used with treatment, time, treatment-by-time interaction as fixed effects and baseline, age, gender, ApoE genotype, site as covariates.

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.