GLP-1 Peptide Atlas, by Delfa

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TerminatedPhase 2Results posted

A Pilot Clinical Trial of Exendin-4 in Alzheimer's Disease

A Pilot Study of Exendin-4 in Alzheimer s Disease

Lead sponsor

National Institute on Aging (NIA)

Asset

Exenatide

GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

actual

Study population

Alzheimer's / cognition

Key I/E criterion

—

Primary endpoint

•Nausea

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

NCT IDNCT01255163

Org study ID100423

Secondary ID10-AG-0423

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

Investigational agents

Exenatide

Study populations

Who this study enrolls

Alzheimer's / cognition

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 (9)

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 clinical outcomes

Weight & body composition

Cardiometabolic biomarkers

Safety / tolerability / PK

Weight & body composition

1 endpoint

Secondary/protocol endpoint

Body Mass Index (BMI)

Time frame:18 months

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), kg/m^2	95% CI
Exendin-4	25.867	—
Placebo	25.789	—

p0.009Mixed Models Analysis

Cardiometabolic biomarkers

1 endpoint

Secondary/protocol endpoint

Cerebrospinal Fluid Amyloid-beta 42 (CSF Abeta42)

Time frame:18 months

change from baseline, improvement

Posted result

Group	Value (mean), pg/dl	95% CI
Exendin-4	177.43	—
Placebo	176.38	—

p0.018Mixed Models Analysis

Safety / tolerability / PK

1 endpoint

Primary/protocol endpoint

Number of Participants With Incidence of Nausea

Time frame:18 months

Nausea

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Exendin-4	5	—
Placebo	0	—

p0.016Fisher Exact

Other clinical outcomes

6 endpoints

Secondary/protocol endpoint

Mini Mental State Examination (MMSE)

Time frame:18 months

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	95% CI
Exendin-4	23.11	—
Placebo	23.11	—

p0.098Mixed Models Analysis

Secondary/protocol endpoint/low confidence

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

Time frame:18 months

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	95% CI
Exendin-4	16	—
Placebo	17.78	—

p0.295Mixed Models Analysis

Secondary/protocol endpoint

Clinical Dementia Rating (CDR) Global Score

Time frame:18 months

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	95% CI
Exendin-4	0.889	—
Placebo	0.833	—

p0.141Mixed Models Analysis

Secondary/protocol endpoint

Clinical Dementia Rating (CDR) Sum of Boxes

Time frame:18 months

descriptive, improvement

Posted result

Group	Value (mean), units on a scale	95% CI
Exendin-4	4.778	—
Placebo	4.5	—

p0.031Mixed Models Analysis

Secondary/protocol endpoint

Cerebrospinal Fluid (CSF) Total Tau

Time frame:18 months

change from baseline, improvement

Posted result

Group	Value (mean), pg/dl	95% CI
Exendin-4	86.57	—
Placebo	70.75	—

p0.703Mixed Models Analysis

Secondary/protocol endpoint

Cerebrospinal Fluid phospho181-tau (CSF p181-tau)

Time frame:18 months

CSF PTAU181

change from baseline, improvement

Posted result

Group	Value (mean), pg/dl	95% CI
Exendin-4	54.57	—
Placebo	44.25	—

p0.845Mixed 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

Novel Hominid-Specific IAPP Isoforms: Potential Biomarkers of Early Alzheimer's Disease and Inhibitors of Amyloid Formation.
Biomolecules2023 Jan 13PMID36671553doi:10.3390/biom13010167via clinicaltrials gov reference derived + pubmed nct search
A Pilot Study of Exenatide Actions in Alzheimer's Disease.
Current Alzheimer research2019 (year)PMID31518224doi:10.2174/1567205016666190913155950via clinicaltrials gov reference derived + pubmed nct search
Glucagon-like Peptide-1 and the Central/Peripheral Nervous System: Crosstalk in Diabetes.
Trends in endocrinology and metabolism: TEM2017 Feb (month)PMID27871675doi:10.1016/j.tem.2016.10.001via clinicaltrials gov reference derived + pubmed nct search
An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Aβ oligomers.
The Journal of clinical investigation2012 Apr (month)PMID22476196doi:10.1172/JCI57256via CT.gov background
Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease.
The Lancet. Neurology2011 Feb (month)PMID21147038doi:10.1016/S1474-4422(10)70277-5via CT.gov background

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

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 1, 2026 snapshot.