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

The University of Texas System (UT)

Status and phase

Completed

Early Phase 1

Conditions

Alzheimer Disease

Cognitive Impairment, Mild

Treatments

Drug: Rapamune

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT04200911

UL1TR002645 (U.S. NIH Grant/Contract)

HSC20190850H

Details and patient eligibility

About

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

Full 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.

Enrollment

10 patients

Sex

All

Ages

55 to 85 years old

Volunteers

Accepts Healthy Volunteers

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