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

NCT ID: NCT04200911

Last Updated: 2025-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2022-01-13

Brief Summary

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

Detailed 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.

Conditions

Cognitive Impairment, Mild; Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RAPA intervention

Sirolimus 1mg orally once a day for 8 weeks

Group Type: EXPERIMENTAL

Rapamune

Intervention Type: DRUG

Sirolimus 1mg capsules

Interventions

Rapamune

Sirolimus 1mg capsules

Intervention Type: DRUG

Other Intervention Names

Sirolimus

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mitzi Gonzales, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Health San Antonio

Locations

UTHSA McDermott Clinical Sciences Building

San Antonio, Texas, United States

Countries

United States

References

Gonzales MM, Garbarino VR, Kautz TF, Song X, Lopez-Cruzan M, Linehan L, Van Skike CE, De Erausquin GA, Galvan V, Orr ME, Musi N, He Y, Bateman RJ, Wang CP, Seshadri S, Kraig E, Kellogg D Jr. Rapamycin treatment for Alzheimer's disease and related dementias: a pilot phase 1 clinical trial. Commun Med (Lond). 2025 May 20;5(1):189. doi: 10.1038/s43856-025-00904-9.

Reference Type: DERIVED

PMID: 40394335 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

UL1TR002645

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC20190850H

Identifier Type: -

Identifier Source: org_study_id