Clinical trial NCT04629495: Rapamycin - Effects on Alzheimer's and Cognitive Health
Official title: Rapamycin - Effects on Alzheimer's and Cognitive Health (REACH)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Alzheimer Disease
Keywords: Cognition
Alzheimer's disease biomarkers
Neuroimaging
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2020-11-16
Enrollment: 40
Sex: ALL
Minimum age (years): 55
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo controlled study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of adverse events
timeFrame: Baseline to 12 months
measure: Change in glucose level
timeFrame: Baseline to 12 months
measure: Change in albumin
timeFrame: Baseline to 12 months
measure: Change in carbon dioxide or bicarbonate (CO2)
timeFrame: Baseline to 12 months
measure: Change in calcium
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Central nervous system penetration of rapamycin
timeFrame: Baseline and 12 months
measure: Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5)
timeFrame: Baseline to 12 months
measure: Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB)
timeFrame: Baseline to 12 months
measure: Change in Functional status
timeFrame: Baseline to 12 months
measure: Change in Neuropsychiatric symptoms
timeFrame: Baseline to 12 months
measure: Change in Gait Speed
timeFrame: Baseline to 12 months
measure: Change in Grip Strength
timeFrame: Baseline to 12 months
measure: Change in CSF amyloid beta
timeFrame: Baseline to 12 months
measure: Change in cerebral glucose metabolism
timeFrame: Baseline to 12 months
measure: Change in Brain Volumetry
timeFrame: Baseline to 12 months
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases
state: Texas
Study officials:
affiliation: UT Health San Antonio
name: Sudha J Seshadri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UT Health San Antonio
name: Mitzi J Gonzales, PhD
role: PRINCIPAL_INVESTIGATOR
References: