Rapamycin - Effects on Alzheimer's and Cognitive Health

NCT ID: NCT04629495

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-11
• Study Completion Date: 2026-03-31

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).

Detailed Description

The study will consist of a screening/baseline period of up to 90 days pre-study drug, with a 12-month (+3 day) treatment period with rapamycin, followed by a post-treatment assessment completed within 14 days of the final study drug dose, and a final assessment conducted 6-months (+14 days) after the final study drug dose. The study duration is not expected to exceed 90 weeks for participants.

Conditions

Mild Cognitive Impairment; Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

RAPA (rapamycin) treatment group

Subjects will receive active drug

Group Type: ACTIVE_COMPARATOR

Rapamycin

Intervention Type: DRUG

RAPA will be administered orally 1mg daily

Placebo group

Subjects will receive placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo will be administered orally once daily

Interventions

Rapamycin

RAPA will be administered orally 1mg daily

Intervention Type: DRUG

Placebo

Placebo will be administered orally once daily

Intervention Type: OTHER

Other Intervention Names

Sirolimus, RAPA; Placebo capsule

Eligibility Criteria

Inclusion Criteria

1. Both genders and all ethnic groups

2. Ages 55 to 89 years

3. 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)

4. Amyloid positivity based on Amyloid PET Imaging

5. 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

6. 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

7. Stable dose of AD medications (Donepezil, rivastigmine, Memantine, galantamine) for at least three months is allowed

Exclusion Criteria

1. Diabetes (HBA1c≥6.5% or antidiabetic medications)

2. History of skin ulcers or poor wound healing

3. Current tobacco or illicit drug use or alcohol abuse

4. Use of anti-platelet or anti-coagulant medications other than aspirin

5. Current medications that affect cytochrome 450 3A4 (CYP3A4)

6. Immunosuppressant therapy within the last year

7. Chemotherapy or radiation treatment within the last year

8. Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities

9. Untreated hypertriglyceridemia (fasting triglycerides < 250 mg/dl)

10. Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%)

11. Chronic heart failure

12. Pregnancy or lactation

13. Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack

14. Significant neurological conditions other than AD or MCI

15. Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg - based on two readings)

16. Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or severe mental illness

17. History of, or MRI, or CT positive for, any space occupying lesion, including mass effect or abnormal intracranial pressure, which would indicate contraindications to lumbar puncture

18. Organ transplant recipients

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alzheimer's Association

OTHER

Sponsor Role: collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sudha J Seshadri, MD

Role: PRINCIPAL_INVESTIGATOR

UT Health San Antonio

Locations

Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sudha Seshadri, MD

Role: CONTACT

seshadri@uthscsa.edu

210-450-8437

Floyd A Jones

Role: CONTACT

jonesfa@uthscsa.edu

210-450-3158

Facility Contacts

Sudha Seshadri, MD

Role: primary

Seshadri@uthscsa.edu

210-450-8437

Floyd A Jones

Role: backup

(210) 450-3518

Other Identifiers

HSC20200763H

Identifier Type: -

Identifier Source: org_study_id