A Pilot Clinical Trial of Exendin-4 in Alzheimer's Disease - Alzheimer’s Disease & Related Dementias Atlas

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

Secondary10-AG-0423

Org study ID100423

NCT IDNCT01255163

Timeline

Milestones

Study start2010-11-21

Study first posted2010-12-07estimated

Primary completion2016-11-18actual

Study completion2016-11-18actual

Last update posted2018-02-22actual

Results first posted2018-02-22actual

Assets

Drug assets

Exendin-4

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age60 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•INCLUSION CRITERIA:

•Age > 60

•Clinical Dementia Rating (global CDR) of 0.5 or 1. Memory box score must be at least 0.5.

•Mini Mental Status Exam (MMSE) > 20

•Clinical diagnosis of (amnestic or mixed) MCI or early AD and Memory deficit on neuropsychological or clinical testing.

•Hamilton Depression Scale score of less than or equal to 12 on the 17-item scale

•CSF A beta 42 < 192 (+- 10%) pg/ml (given an intra-subject laboratory variability ~ 10%)

•Medications stable for at least 4 weeks prior to screening. In particular:

-Participants may take stable doses of antidepressants, chronic anxiolytics or sedative hypnotics, if started at least 4 weeks or longer prior to screening

-Cholinesterase inhibitors and/or memantine are allowable, if started at least 4 weeks prior to screening

-Participants will not be asked to discontinue medications without permission from their primary care provider (PCP) or specialist.

•Fluency in English

•At the time of enrollment, participants must have the ability to provide informed consent and make health care decisions.

•An informant or caregiver who has frequent contact with the participant (e.g. an average of 10 hours per week or more) must be appointed to serve as Durable Power of Attorney (DPA) for research and medical care at NIA, accompany the participant to clinic visits and provide historical information regarding the participant s cognitive status, and assist participants with/administer injections of the investigational medication.

•Good general health with no additional disease states that could interfere with the study

Exclusion criteria

•Other significant neurological disease of the Central Nervous System (such as Parkinson s disease, atypical Parkinsons disease, Multi-infarct Dementia, Frontotemporal Dementia, Huntington s disease, Normal Pressure Hydrocephalus, brain tumor, Progressive Supranuclear Palsy, Epilepsy, Subdural Hematoma or Multiple Sclerosis)

•A history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities

•Positive RPR or HIV

•Abnormal PT/PTT and INR (1.5 standard deviation over the upper normal limit) increasing the risk for LP related bleeding/hematoma; platelet count <100,000/microliters.

•Anti-coagulant therapy (such as coumadin). Aspirin up to 325 is allowed.

•Investigators unable to obtain CSF, failure of Lumbar Puncture after a limited number of unsuccessful attempts).

•History of psychiatric disease with significant impairment in thought processes (e.g. schizophrenia, bipolar disease, psychosis). Participants who develop psychiatric conditions necessitating treatment after their enrollment will not be dropped from the study. The high incidence of late-onset depression and anxiety among individuals with MCI and AD requires that participants with depression, and/or anxiety should not be excluded from the cohort to maintain the ecological validity of the results.

•Current abuse of alcoholic beverages (> 7 in women and >14 in men) or substance abuse.

•Known diagnosis of diabetes at the time of enrollment or new diagnosis of diabetes based on the findings of elevated fasting blood glucose (= or >126 mg/dl) and/or the oral glucose tolerance test at screening (>200 mg/dl at two hours).

•Severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease. Individuals with moderate renal impairment (creatinine clearance 30 to 50 ml/min) may be enrolled in the study, but their BUN and Creatinine will be monitored during each visit after drug initiation and extra safety visits will be conducted at 3, 9, and 15 months.

•Current or previous treatment with Exendin-4 (Exenatide, trade name Byetta.)

•History of pancreatitis, active upper GI, hepatic or gallbladder disease

•Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2

•History of repeated hypoglycemia

•Body mass index (BMI) < 18 on enrollment (given the expected weight loss caused by Exendin-4 and dementia). In the BLSA, participants with age > 65 had a mean BMI of 25.8 with SD of 3.9 Exendin-4 has been shown to cause an average 5.3 kg weight loss, with 95% CI: 6 to 4.5 kg (126).

•Allergy to Exendin-4 or to substances in the injection pen (metacresol, mannitol, glacial acetic acid, sodium acetate trihydrate, water for injection).

•Participation in other studies of investigational treatments for Alzheimer s disease in the last year.

Endpoints (18)

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

Global cognition

6

Other (unclassified)

4

Amyloid biomarkers

2

Tau biomarkers

2

Fluid / digital biomarkers

2

Safety / tolerability / PK

2

Global cognition

6 endpoints

Secondary/protocol endpoint

Mini Mental State Examination (MMSE)

Time frame:18 months

Mini-Mental State Examination (MMSE)

descriptive

Secondary/protocol endpoint

Clinical Dementia Rating (CDR) Global Score

Time frame:18 months

descriptive

Secondary/protocol endpoint

Clinical Dementia Rating (CDR) Sum of Boxes

Time frame:18 months

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

descriptive

Secondary/registry result

Mini Mental State Examination (MMSE)

Time frame:18 months

Mini-Mental State Examination (MMSE)

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
Exendin-4n=13 Participants	23.11	6.009
Placebon=14 Participants	23.11	5.011

p0.098Mixed Models Analysis

Secondary/registry result

Clinical Dementia Rating (CDR) Global Score

Time frame:18 months

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
Exendin-4n=9 Participants	0.889	0.6509
Placebon=9 Participants	0.833	0.5

p0.141Mixed Models Analysis

Secondary/registry result

Clinical Dementia Rating (CDR) Sum of Boxes

Time frame:18 months

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
Exendin-4n=9 Participants	4.778	4.0782
Placebon=9 Participants	4.5	2.3318

p0.031Mixed Models Analysis

Amyloid biomarkers

2 endpoints

Secondary/protocol endpoint

Cerebrospinal Fluid Amyloid-beta 42 (CSF Abeta42)

Time frame:18 months

descriptive

Secondary/registry result

Cerebrospinal Fluid Amyloid-beta 42 (CSF Abeta42)

Time frame:18 months

descriptive

Posted result

Group	Value (mean), pg/dl	Standard deviation
Exendin-4n=9 Participants	177.43	70.720
Placebon=9 Participants	176.38	30.528

p0.018Mixed Models Analysis

Tau biomarkers

2 endpoints

Secondary/protocol endpoint

Cerebrospinal Fluid (CSF) Total Tau

Time frame:18 months

descriptive

Secondary/registry result

Cerebrospinal Fluid (CSF) Total Tau

Time frame:18 months

descriptive

Posted result

Group	Value (mean), pg/dl	Standard deviation
Exendin-4n=9 Participants	86.57	37.434
Placebon=9 Participants	70.75	33.148

p0.703Mixed Models Analysis

Fluid / digital biomarkers

2 endpoints

Secondary/protocol endpoint

Cerebrospinal Fluid phospho181-tau (CSF p181-tau)

Time frame:18 months

descriptive

Secondary/registry result

Cerebrospinal Fluid phospho181-tau (CSF p181-tau)

Time frame:18 months

descriptive

Posted result

Group	Value (mean), pg/dl	Standard deviation
Exendin-4n=9 Participants	54.57	32.893
Placebon=9 Participants	44.25	19.739

p0.845Mixed Models Analysis

Safety / tolerability / PK

2 endpoints

Primary/protocol endpoint

Number of Participants With Incidence of Nausea

Time frame:18 months

event count, event

Primary/registry result

Number of Participants With Incidence of Nausea

Time frame:18 months

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Exendin-4n=13 Participants	5	-
Placebon=14 Participants	0	-

p0.016Fisher Exact

Other (unclassified)

4 endpoints

Secondary/protocol endpoint/low confidence

Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog70)

Time frame:18 months

ADAS-Cog

descriptive

Secondary/protocol endpoint/low confidence

Body Mass Index (BMI)

Time frame:18 months

descriptive

Secondary/registry result/low confidence

Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog70)

Time frame:18 months

ADAS-Cog

descriptive

Posted result

Group	Value (mean), units on a scale	Standard deviation
Exendin-4n=9 Participants	16	8.588
Placebon=9 Participants	17.78	8.643

p0.295Mixed Models Analysis

Secondary/registry result/low confidence

Body Mass Index (BMI)

Time frame:18 months

descriptive

Posted result

Group	Value (mean), kg/m^2	Standard deviation
Exendin-4n=9 Participants	25.867	3.6284
Placebon=9 Participants	25.789	4.6023

p0.009Mixed Models Analysis

Publications (5)

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

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.