Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway
Purpose
Evaluation of central nervous system penetration of orally administered Rapamune (RAPA) in older adults with Mild Cognitive Impairment (MCI) or early Alzheimer's disease (AD) and investigate associated safety, tolerability, target engagement, cognition, and functional status as initial proof-of-concept study
Conditions
- Cognitive Impairment, Mild
- Alzheimer Disease
Eligibility
- Eligible Ages
- Between 55 Years and 85 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Diagnosis of Mild Cognitive Impairment (MCI), Clinical Dementia Rating Scale (CDR)=0.5-1; Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall ≤5% based on age-adjusted normal values, clinician approved - Normal blood cell counts without clinically significant excursions - A Legally Authorized Representative (LAR) if necessary for consent - An LAR or study partner to accompany participant to all visits - Availability for all study visits - Stable dose of AD medications) Donepezil, rivastigmine, memantine, galantamine) for at least 3 months
Exclusion Criteria
- Diabetes (HbA1c≥6.5% or anti-diabetic medications) - History of skin ulcers or poor wound healing - Current tobacco or illicit drug use or alcohol abuse - Use of anti-platelet or anti-coagulant medications other than aspirin - Current medications that affect cytochrome P450 3A4 - Immunosuppressant therapy within the last year - Chemotherapy or radiation treatment within the last year - Current or chronic history of liver disease or known hepatic or biliary abnormalities - Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%) - Chronic heart failure - Pregnancy - Recent history (past 6 months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack - significant neurological conditions other than AD - Poorly controlled blood pressure (systolic BP>160, diastolic BP>90mmHg) - Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or psychiatric disease - History of, or Magnetic Resonance Imaging (MRI) positive for any space occupying lesion, including mass effect and/or abnormal intracranial pressure, which would indicate contraindication to lumbar puncture
Study Design
- Phase
- Early Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental RAPA intervention |
Sirolimus 1mg orally once a day for 8 weeks |
|
More Details
- Status
- Completed
- Sponsor
- The University of Texas Health Science Center at San Antonio
Study Contact
Detailed Description
This study is an open-label pilot study of orally administered RAPA to measure its target engagement in Cerebrospinal Fluid (CSF) and blood, and to establish the feasibility and safety of RAPA treatment in older adults with MCI and early stage AD as initial proof-of-concept for a larger Phase 2 clinical trial.