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

Early Phase 1CompletedNCT04200911

The University of Texas Health Science Center at San Antonio10 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cognitive Impairment, Mild Alzheimer Disease

Interventions

RapamuneDRUG

Sirolimus 1mg capsules

Eligibility

Sex: ALLMin age: 55 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

UTHSA McDermott Clinical Sciences Building

San Antonio, Texas, United States

Outcomes

Primary Outcomes

Blood Brain Barrier Penetration of RAPA

Lumbar punctures will be performed at baseline and after the final RAPA dose, to assess CSF levels of the drug. Change is calculated as value at 8 weeks minus the value at baseline.

Time frame: Change from Baseline to 8 weeks

Secondary Outcomes

Adverse Events

Number of adverse events experienced across all 10 subjects after they were enrolled and randomized to treatment, regardless of relatedness to intervention.