Phase 2 · Exenatide

NCT01255163 trial results

A Pilot Study of Exendin-4 in Alzheimer s Disease

Number of Participants With Incidence of Nausea (Participants), 18 months. Exendin-4: 5; Placebo: 0.

Participants
57
Status
terminated
Completed
2016-11-18
Sponsor
National Institute on Aging (NIA)

As posted on ClinicalTrials.gov (NCT01255163), updated at source Feb 22, 2018. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What NCT01255163 measured first

Number of Participants With Incidence of NauseaParticipants · 18 months · count of participants
Exendin-4n=13Placebon=14
50
Side effects by arm

Side effects in NCT01255163

Percent of participants affected, Up to 18 months. The most common events the registry lists.

EventExendin-4Placebo
Any serious event7.7%7.1%
Nausea38.5%0%
Loss of appetite/weight loss30.8%0%
Diarrhea23.1%7.1%
Hypoglycemia symptoms23.1%14.3%
Post lumbar puncture headache23.1%21.4%
Gastroesophageal reflux disease15.4%7.1%
Pancreatic enzyme elevation15.4%14.3%
Abnormal kidney function tests15.4%14.3%
Fatigue15.4%0%
Orthopedic injuries15.4%14.3%
Vasovagal syncope15.4%0%
Thyroid abnormalities7.7%14.3%
Lower abdominal pain7.7%0%
Injection site ecchymosis and pain7.7%7.1%
Vomiting7.7%0%
Gout7.7%0%
Influenza7.7%0%
Tinnitus7.7%0%
Allergic conjuctivitis7.7%0%
Lacunar stroke0%7.1%
Floaters0%7.1%
Dyspnea on exertion0%7.1%
Secondary outcomes

What else it measured

Mini Mental State Examination (MMSE)units on a scale · 18 months · mean
Exendin-4n=13Placebon=14
23.11(6.009)23.11(5.011)
Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog70)units on a scale · 18 months · mean
Exendin-4n=9Placebon=9
16(8.588)17.78(8.643)
Clinical Dementia Rating (CDR) Global Scoreunits on a scale · 18 months · mean
Exendin-4n=9Placebon=9
0.889(0.6509)0.833(0.5)
Clinical Dementia Rating (CDR) Sum of Boxesunits on a scale · 18 months · mean
Exendin-4n=9Placebon=9
4.778(4.0782)4.5(2.3318)
Cerebrospinal Fluid (CSF) Total Taupg/dl · 18 months · mean
Exendin-4n=9Placebon=9
86.57(37.434)70.75(33.148)
Cerebrospinal Fluid phospho181-tau (CSF p181-tau)pg/dl · 18 months · mean
Exendin-4n=9Placebon=9
54.57(32.893)44.25(19.739)
Cerebrospinal Fluid Amyloid-beta 42 (CSF Abeta42)pg/dl · 18 months · mean
Exendin-4n=9Placebon=9
177.43(70.720)176.38(30.528)
Body Mass Index (BMI)kg/m^2 · 18 months · mean
Exendin-4n=9Placebon=9
25.867(3.6284)25.789(4.6023)
The trial

How NCT01255163 was run

Background: Exendin-4 (or Exenatide) is a medication currently used to treat diabetes that has shown promising results in animal and cellular models of Alzheimer's disease. It is possible that Exendin-4 may be a treatment for Alzheimer's disease, which involves the gradual deterioration and death of neurons. Researchers are interested in studying the safety and comparing the effects of Exendin-4 with placebo on cognitive performance, clinical progression of dementia, various chemicals measured in blood and cerebrospinal fluid, and brain MRI, in individuals with early-stage Alzheimer's disease or mild cognitive impairment. Objectives: To determine the safety and tolerability of twice daily administration of Exendin-4, as well as to acquire preliminary evidence for effects on cognitive performance, clinical progression of dementia, various chemicals measured in blood and cerebrospinal fluid, and brain MRI, in individuals with early-stage Alzheimer's disease or mild cognitive impairment. Eligibility: Individuals at least 60 years of age who have objective evidence of early-stage Alzheimer's disease or mild cognitive impairment in screening testing. Design: * Participants will be screened. * Following the telephone screening, two in-person screening visits to determine eligibility. * The screening visit will involve a medical history and neurological examination, tests of memory and cognition, a lumbar puncture, collection of blood and saliva samples, and brain Magnetic Resonance Imagine (MRI) studies. Participants will be required to appoint a Durable Power of Attorney for research and medical care during this protocol. * Eligible participants will be divided into two groups (double-blind randomization). One group will receive Exendin-4 SC twice daily, and the...

  • Exendin-4: Exenatide 5 mcg or 10 mcg SC twice daily
  • Placebo: Placebo SC twice daily
Who could join the trial

* 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...

Published papers

Papers from NCT01255163

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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