AzTrials
AzTrials

Alzheimer's DiseasePhase 2NCT01255163

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

A Phase 2 study testing Exendin-4 SC in people with Alzheimer's Disease and Mild Cognitive Impairment, run by National Institute on Aging (NIA) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 60 years and older
What is being tested?
Exendin-4 SC
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
57 participants
Where
1 siteUnited States
Study dates
21 Nov 2010to 18 Nov 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
Show all 14Show fewer
  • 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.

Who cannot join

  • 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).
Show all 17Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institute on Aging, Clinical Research Unit

    Baltimore, Maryland, 21224

Other trials in United States

About this study

Official title: A Pilot Study of Exendin-4 in Alzheimer s Disease

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.

Read more

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 other will receive a placebo. Participants will keep a medication diary and will be scheduled for additional study visits 1 and 2 weeks after the start of the treatment.
  • Participants will have regular followup visits with blood tests, cognitive tests, imaging studies, and other examinations 6, 12, and 18 months after the start of the treatment. Another lumbar puncture may be performed optionally at the 18-month followup visit.
Read the detailed description

Objective: Exendin-4 (or exenatide) is a medication currently used in the treatment of diabetes mellitus (DM). Exendin-4 has generated promising results as an agent protecting neurons from a number of assaults both in the laboratory and in studies on animals. Specifically, there is pre-clinical evidence that Exendin-4 may be a treatment for Alzheimer's disease (AD). Based on these facts, we conducted a pilot Phase II double blind randomized placebo-controlled clinical study to assess the safety and provide proof of concept for exendin-4 treatment in early Alzheimer's disease (AD), by demonstrating a response of disease biomarkers to the intervention. Our main hypothesis is that long-term administration of Exendin-4 in participants with amnestic MCI/early AD in FDA-approved doses is safe and will induce a change over time in AD biomarkers. Subject population: We intend to screen up to 100 potential participants in order to ensure that at least 40 participants (enrolled based on a clinical diagnosis of amnestic MCI/early AD and Cerebrospinal Fluid (CSF) biomarker evidence of AD) will be enrolled into treatment and complete the study. Design: Enrolled participants will be randomly assigned into one of two groups (Exendin-4 vs. Placebo) and will be followed at regular intervals for 18 months. Outcome measures: Safety and tolerability will be the primary outcomes. In addition, we will measure and assess the change over time of a number of exploratory outcomes with the intervention, including CSF and plasma biomarkers (such as CSF A42, tau, p181-tau and plasma A42/A40), cognitive performance measures (such as the Alzheimer's Disease Assessment scale, cognitive sub-scale, and other tests), clinical progression of dementia measures (such as the Clinical Dementia Rating scale sum-of-boxes), volumetric changes on structural brain MRI and changes in resting fMRI. All research will be performed on the National Institute on Aging (NIA) Clinical Research Unit located on the 5th floor of Harbor Hospital.

Being tested
Exendin-4 SC, Placebo SC
Keywords
Alzheimer's, Brain insulin resistance, Diabetes
Medical subject headings
Alzheimer Disease, Cognitive Dysfunction, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Exendin-4 SCDrug

    Also called Exenatide SC

    Exenatide 5 mcg or 10 mcg SC twice daily

  • Placebo SCDrug

    Also called Placebo SC twice daily

    Placebo SC twice daily

Study groups in NCT01255163
Study groupRoleWhat they receive
Exendin-4ExperimentalExenatide 5 mcg or 10 mcg SC twice daily
Receives: Drug: Exendin-4 SC
PlaceboPlacebo comparatorPlacebo SC twice daily
Receives: Drug: Placebo SC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Incidence of Nausea

    Tolerability of exenatide (nausea is the most common expected adverse event of exenatide)

    Measured: 18 months

Secondary outcomes (8)

  1. Mini Mental State Examination (MMSE)

    Scale range: 0 - 30 points (higher is better)

    Measured: 18 months

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

    Alzheimer's dementia scale cognitive sub-scale range: 0 - 70 points (higher is worse)

    Measured: 18 months

  3. Clinical Dementia Rating (CDR) Global Score

    Clinical Dementia Rating global score range: 0 (no dementia); 0.5 (Mild Cognitive Impairment); 1 (mild dementia); 2 (moderate dementia); 3 (severe dementia). Higher is worse.

    Measured: 18 months

  4. Clinical Dementia Rating (CDR) Sum of Boxes

    Sum of the Clinical Dementia Rating "boxes" (memory, orientation, judgment and problem solving, community affairs, home and hobbies, personal care). Each box is rated as 0, 0.5, 1, 2 or 3. Range for the sum of boxes is 0 - 18. Higher scores reflect a greater severity of dementia.

    Measured: 18 months

  5. Cerebrospinal Fluid (CSF) Total Tau

    Total Tau measured in CSF using Luminex xMAP technology and INNO-BIA Alz Bio3 kits (Research Use Only) provided by Fujirebio

    Measured: 18 months

  6. Cerebrospinal Fluid phospho181-tau (CSF p181-tau)

    p-181-Tau measured in CSF using Luminex xMAP technology and INNO-BIA Alz Bio3 kits (Research Use Only) provided by Fujirebio

    Measured: 18 months

  7. Cerebrospinal Fluid Amyloid-beta 42 (CSF Abeta42)

    Abeta42 peptide measured in CSF using Luminex xMAP technology and INNO-BIA Alz Bio3 kits (Research Use Only) provided by Fujirebio

    Measured: 18 months

  8. Body Mass Index (BMI)

    Body Mass Index defined as a person's weight in kilograms (kg) divided by his or her height in meters squared.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2010 (estimated)
  2. Study start21 Nov 2010
  3. Primary completion18 Nov 2016
  4. Study completion18 Nov 2016

Why it stopped: AstraZeneca withdrew support for the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double-blind randomized placebo-controlled.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01255163
Sponsor's protocol ID
100423
Other IDs
10-AG-0423
Status last verified
Jan 2018
First submitted
4 Dec 2010
Last updated
22 Feb 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Kapogiannis D, Mattson MP. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease. Lancet Neurol. 2011 Feb;10(2):187-98. doi: 10.1016/S1474-4422(10)70277-5. Epub 2010 Dec 10.

    PubMed 21147038

  • Bomfim TR, Forny-Germano L, Sathler LB, Brito-Moreira J, Houzel JC, Decker H, Silverman MA, Kazi H, Melo HM, McClean PL, Holscher C, Arnold SE, Talbot K, Klein WL, Munoz DP, Ferreira ST, De Felice FG. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Abeta oligomers. J Clin Invest. 2012 Apr;122(4):1339-53. doi: 10.1172/JCI57256.

    PubMed 22476196

  • Liu QR, Zhu M, Chen Q, Mustapic M, Kapogiannis D, Egan JM. Novel Hominid-Specific IAPP Isoforms: Potential Biomarkers of Early Alzheimer's Disease and Inhibitors of Amyloid Formation. Biomolecules. 2023 Jan 13;13(1):167. doi: 10.3390/biom13010167.

    PubMed 36671553

  • Mullins RJ, Mustapic M, Chia CW, Carlson O, Gulyani S, Tran J, Li Y, Mattson MP, Resnick S, Egan JM, Greig NH, Kapogiannis D. A Pilot Study of Exenatide Actions in Alzheimer's Disease. Curr Alzheimer Res. 2019;16(8):741-752. doi: 10.2174/1567205016666190913155950.

    PubMed 31518224

  • Muscogiuri G, DeFronzo RA, Gastaldelli A, Holst JJ. Glucagon-like Peptide-1 and the Central/Peripheral Nervous System: Crosstalk in Diabetes. Trends Endocrinol Metab. 2017 Feb;28(2):88-103. doi: 10.1016/j.tem.2016.10.001. Epub 2016 Oct 27.

    PubMed 27871675

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Exendin-4 SC in people with Alzheimer's Disease and Mild Cognitive Impairment, run by National Institute on Aging (NIA) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Incidence of Nausea (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01255163, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in