Alzheimer Disease, Mild Cognitive Impairment
Conditions
Keywords
Cognition, Alzheimer's disease biomarkers, Neuroimaging
Brief summary
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).
Detailed description
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.
Interventions
DRUGRapamycin
RAPA will be administered orally 1mg daily
OTHERPlacebo
Placebo will be administered orally once daily
Sponsors
The University of Texas Health Science Center at San Antonio
Alzheimer's Association
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple-blind
Intervention model description
placebo controlled study
Eligibility
Sex/Gender
ALL
Age
55 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
1. Both genders and all ethnic groups 2. Ages 55 to 89 years 3. Diagnosis of MCI or AD (Mini Mental Status Examination (MMSE): 18-30; Clinical Dementia Rating Scale (CDR) = 0.5 - 1; California Verbal Learning Test III (CVLT-III) Delayed Recall ≤16% based on age-adjusted norms, clinician approval) 4. Amyloid positivity based on Amyloid PET Imaging 5. Labs: Normal blood cell counts without clinically significant excursions; normal liver and renal function; and glucose control (HbA1c \< 6.5%). Fasting lipid panel and prothrombin time/prothrombin time test/international normalized ration (PT/PTT/INR) within normal limits 6. A legally authorized representative (LAR) designated to sign informed consent (if necessary) must attend the Screening visit and accompany the participant to all remaining visits to provide reported outcomes 7. Stable dose of AD medications (Donepezil, rivastigmine, Memantine, galantamine) for at least three months is allowed
Exclusion criteria
1. Diabetes (HBA1c≥6.5% or antidiabetic medications) 2. History of skin ulcers or poor wound healing 3. Current tobacco or illicit drug use or alcohol abuse 4. Use of anti-platelet or anti-coagulant medications other than aspirin 5. Current medications that affect cytochrome 450 3A4 (CYP3A4) 6. Immunosuppressant therapy within the last year 7. Chemotherapy or radiation treatment within the last year 8. Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities 9. Untreated hypertriglyceridemia (fasting triglycerides \< 250 mg/dl) 10. Current or chronic history of pulmonary disease or abnormal pulse oximetry (\<90%) 11. Chronic heart failure 12. Pregnancy or lactation 13. Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack 14. Significant neurological conditions other than AD or MCI 15. Poorly controlled blood pressure (systolic BP\>160, diastolic BP\>90 mmHg - based on two readings) 16. Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or severe mental illness 17. History of, or MRI, or CT positive for, any space occupying lesion, including mass effect or abnormal intracranial pressure, which would indicate contraindications to lumbar puncture 18. Organ transplant recipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events | Baseline to 12 months | Development or worsening of medical symptoms or problems |
| Change in glucose level | Baseline to 12 months | A comprehensive metabolic panel is used to measure change in glucose level |
| Change in albumin | Baseline to 12 months | A comprehensive metabolic panel is used to measure change in albumin level |
| Change in carbon dioxide or bicarbonate (CO2) | Baseline to 12 months | A comprehensive metabolic panel is used to measure change in CO2 |
| Change in calcium | Baseline to 12 months | A comprehensive metabolic panel is used to measure change in calcium levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Central nervous system penetration of rapamycin | Baseline and 12 months | A lumbar puncture and blood draw will be used to evaluate levels of study drug |
| Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5) | Baseline to 12 months | 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. |
| Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB) | Baseline to 12 months | 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. |
| Change in Functional status | Baseline to 12 months | 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. |
| Change in Neuropsychiatric symptoms | Baseline to 12 months | 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. |
| Change in Gait Speed | Baseline to 12 months | Gait speed will be evaluated with an electronic gait mat |
| Change in Grip Strength | Baseline to 12 months | Grip strength will be evaluated with a hand dynamometer |
| Change in CSF amyloid beta | Baseline to 12 months | Cerebrospinal fluid (CSF) levels of amyloid beta |
| Change in cerebral glucose metabolism | Baseline to 12 months | Cerebral glucose metabolism is measured using fluorodeoxyglucose-Positron emission tomography (FDG-PET) |
| Change in Brain Volumetry | Baseline to 12 months | Measure of brain volumetry using MRI |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSudha J Seshadri, MD
The University of Texas Health Science Center at San Antonio
Outcome results
None listed