Rapamycin - Effects on Alzheimer's and Cognitive Health

NCT04629495 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HSC20200763H
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Mild Cognitive Impairment; Alzheimer Disease

Keywords

Cognition; Alzheimer's disease biomarkers; Neuroimaging

Outcome Measures

Primary Outcomes (5)

• Number of adverse events

  Development or worsening of medical symptoms or problems

  Baseline to 12 months

• Change in glucose level

  A comprehensive metabolic panel is used to measure change in glucose level

  Baseline to 12 months

• Change in albumin

  A comprehensive metabolic panel is used to measure change in albumin level

  Baseline to 12 months

• Change in carbon dioxide or bicarbonate (CO2)

  A comprehensive metabolic panel is used to measure change in CO2

  Baseline to 12 months

• Change in calcium

  A comprehensive metabolic panel is used to measure change in calcium levels

  Baseline to 12 months

Secondary Outcomes (10)

• Central nervous system penetration of rapamycin

  Baseline and 12 months

• Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5)

  Baseline to 12 months

• Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB)

  Baseline to 12 months

• Change in Functional status

  Baseline to 12 months

• Change in Neuropsychiatric symptoms

  Baseline to 12 months

Study Arms (2)

RAPA (rapamycin) treatment group

ACTIVE COMPARATOR

Subjects will receive active drug

Drug: Rapamycin

Placebo group

PLACEBO COMPARATOR

Subjects will receive placebo

Other: Placebo

Interventions

Rapamycin DRUG

RAPA will be administered orally 1mg daily

Also known as: Sirolimus, RAPA

RAPA (rapamycin) treatment group

Placebo OTHER

Placebo will be administered orally once daily

Also known as: Placebo capsule

Placebo group

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both genders and all ethnic groups
• Ages 55 to 89 years
• 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)
• Amyloid positivity based on Amyloid PET Imaging
• 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
• 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
• Stable dose of AD medications (Donepezil, rivastigmine, Memantine, galantamine) for at least three months is allowed

You may not qualify if:

• Diabetes (HBA1c≥6.5% or antidiabetic 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 450 3A4 (CYP3A4)
• Immunosuppressant therapy within the last year
• Chemotherapy or radiation treatment within the last year
• Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities
• Untreated hypertriglyceridemia (fasting triglycerides \< 250 mg/dl)
• Current or chronic history of pulmonary disease or abnormal pulse oximetry (\<90%)
• Chronic heart failure
• Pregnancy or lactation
• Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
• Significant neurological conditions other than AD or MCI
• Poorly controlled blood pressure (systolic BP\>160, diastolic BP\>90 mmHg - based on two readings)

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• Alzheimer's Association: collaborator

Study Sites (1)

Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Sudha J Seshadri, MD

  UT Health San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sudha Seshadri, MD

CONTACT

210-450-8437; seshadri@uthscsa.edu

Floyd A Jones

CONTACT

210-450-3158; jonesfa@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo controlled study

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: November 16, 2020
• Study Start: August 11, 2021
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At study completion
• Access Criteria: Through journal publication

Locations

US (1)