This study will evaluate the safety, tolerability, and feasibility of 12 month oral rapamycin treatment in older adults with amnestic mild cognitive impairment (aMCI) and early stage Alzheimer's disease (AD).
The study will consist of a screening/baseline period of up to 90 days pre-study drug, with a 12-month (+3 day) treatment period with rapamycin, followed by a post-treatment assessment completed within 14 days of the final study drug dose, and a final assessment conducted 6-months (+14 days) after the final study drug dose. The study duration is not expected to exceed 90 weeks for participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases
San Antonio, Texas, United States
Number of adverse events
Development or worsening of medical symptoms or problems
Time frame: Baseline to 12 months
Change in glucose level
A comprehensive metabolic panel is used to measure change in glucose level
Time frame: Baseline to 12 months
Change in albumin
A comprehensive metabolic panel is used to measure change in albumin level
Time frame: Baseline to 12 months
Change in carbon dioxide or bicarbonate (CO2)
A comprehensive metabolic panel is used to measure change in CO2
Time frame: Baseline to 12 months
Change in calcium
A comprehensive metabolic panel is used to measure change in calcium levels
Time frame: Baseline to 12 months
Central nervous system penetration of rapamycin
A lumbar puncture and blood draw will be used to evaluate levels of study drug
Time frame: Baseline and 12 months
Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5)
Cognition will be measured using the PACC5 scale. The PACC5 is a composite score comprised of measures of global cognition, memory, and executive function. The score reflects an averaged z-score. Scores range from -3 to +3 with higher scores indicating better cognitive performance.
Time frame: Baseline to 12 months
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Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB)
CDR is obtained through semistructured interviews of patients and informants, and cognitive functioning is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. Domain scores are entered into an online algorithm and CDR-SOB score obtained by summing each of the domain box scores, ranging from 0 to 18. A lower score indicates better cognition.
Time frame: Baseline to 12 months
Change in Functional status
Functional status will be measured using the functional assessment scale (FAS). The FAS is completed by a collateral source and assesses ability to complete instrumental activities of daily living. The scale has 10-items and responses range from 0-3. The total score is a sum of the individual items. The total score ranges from 0 to 30 with higher scores indicating more assistance needed.
Time frame: Baseline to 12 months
Change in Neuropsychiatric symptoms
Symptoms will be evaluated using the Geriatric Depression Scale 15 Item (GDS-15). The GDS-15 is a self-report questionnaire with 15 items that have response options of 0 or 1. The total score is the sum of the individual items. The total score on the measure ranges between 0 to 15 with higher scores indicating more depressive symptoms.
Time frame: Baseline to 12 months
Change in Gait Speed
Gait speed will be evaluated with an electronic gait mat
Time frame: Baseline to 12 months
Change in Grip Strength
Grip strength will be evaluated with a hand dynamometer
Time frame: Baseline to 12 months
Change in CSF amyloid beta
Cerebrospinal fluid (CSF) levels of amyloid beta
Time frame: Baseline to 12 months
Change in cerebral glucose metabolism
Cerebral glucose metabolism is measured using fluorodeoxyglucose-Positron emission tomography (FDG-PET)
Time frame: Baseline to 12 months
Change in Brain Volumetry
Measure of brain volumetry using MRI
Time frame: Baseline to 12 months