- Exendin-4 (or Exenatide) is a medication currently used to treat diabetes, but it has shown promising results in tests of its effectiveness in protecting neurons from damaging processes associated with 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 to on congestive performance, overall clinical progression, various chemicals measured in blood and cerebrospinal fluid, and brain MRI, in individuals with early-stage Alzheimer's disease or mild cognitive impairment.
- To determine the safety and tolerability, as well as to acquire preliminary evidence for the effectiveness of twice daily administration of Exendin-4 as a treatment for early-stage Alzheimer s disease or mild cognitive impairment.
- Individuals at least 60 years of age who have objective evidence of early-stage Alzheimer's disease or mild cognitive impairment in screening testing.
- 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. One group will receive Exendin-4, 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, imaging studies, and other examinations 6, 12, and18 months after the start of the treatment. Another lumbar puncture may be performed optionally at the 18-month followup visit.
Primary Outcome Measures:
- Safety and tolerability of Exendin-4 administered twice daily via SC injections [ Time Frame: 18 months ]
Secondary Outcome Measures:
- Behavioral and cognitive performance measures [ Time Frame: 18 months ]
- Changes on structural and functional MRI and MRS [ Time Frame: 18 months ]
- Hormonal and metabolic changes and changes in cerebrospinal fluid and plasma Alzheimer s disease biomarkers. [ Time Frame: 18 months ]
- Clinical Dementia Rating (CDR) scale sum-of-boxes [ Time Frame: 18 months ]
- Alzheimer's Disease Assessment scale - cognitive sub-scale (ADAS-cog) [ Time Frame: 18 months ]
| Estimated Enrollment:
| Study Start Date:
||November 21, 2010
| Study Completion Date:
||November 18, 2016
| Primary Completion Date:
||November 18, 2016 (Final data collection date for primary outcome measure)
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 propose a pilot Phase II double blind randomized placebo-controlled clinical study to assess the safety and provide proof of concept for efficacy of 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 biochemical biomarkers (such as CSF BDNF, 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), overall clinical progression measures (such as the Clinical Dementia Rating scale sum-of-boxes), volumetric changes on structural brain MRI and changes in default mode network activation on 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.