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

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.