Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway

Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway (CARPE DIEM)

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

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.

Inclusion Criteria:

• Diagnosis of Mild Cognitive Impairment (MCI) or Alzheimer's disease, Global Clinical Dementia Rating Scale (CDR)=0.5-1
• Normal blood cell counts without clinically significant excursions; ; normal liver and renal function; and glucose control (HbA1c < 6.5%). Lipid panel and PT/PTT/INR within normal limits
• 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 prior to the baseline visit

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; current or recent medications for hypertriglyceridemia (eg, Gemfibrozil)
• Hypersensitivity or history of allergy to Rapamycin
• Immunosuppressant therapy within the last year; current treatment with hydroxychloroquine and chloroquine (requires "washout period" of 14 days)
• Chemotherapy or radiation treatment within the last year
• Current or chronic history of liver disease or known hepatic or biliary abnormalities
• History of primary hypertriglyceridemia. Abnormal triglycerides >200 or LDL cholesterol >193, or other abnormal labs deemed clinically significant upon investigator review
• 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, COVID-19, 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
• Organ transplant recipients