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

NCT04200911 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: HSC20190850HUL1TR002645
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Conditions

Cognitive Impairment, Mild; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  Change from Baseline to 8 weeks

Secondary Outcomes (41)

• Adverse Events

  Baseline to 8 weeks

• Change in Vitals From Baseline to 8 Weeks

  Baseline to 8 weeks

• Percentage of Study Drug Pills Taken

  Baseline to 8 weeks

• Change in CSF AD Biomarkers From Baseline to 8 Weeks

  Baseline to 8 weeks

• Change in Plasma AD Biomarkers From Baseline to 8 Weeks

  Baseline to 8 weeks

Study Arms (1)

RAPA intervention

EXPERIMENTAL

Sirolimus 1mg orally once a day for 8 weeks

Drug: Rapamune

Interventions

Rapamune DRUG

Sirolimus 1mg capsules

Also known as: Sirolimus

RAPA intervention

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

UTHSA McDermott Clinical Sciences Building

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 40394335 DERIVED

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

Results Point of Contact

• Title: Mitzi Gonzales, PhD
• Organization: UT Health San Antonio

Gonzalesm20@uthscsa.edu

210-450-9047

Study Officials

• Mitzi Gonzales, PhD

  UT Health San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2019
• First Posted: December 16, 2019
• Study Start: June 1, 2020
• Primary Completion: January 13, 2022
• Study Completion: January 13, 2022
• Last Updated: January 8, 2025
• Results First Posted: March 21, 2023

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After publication in a peer reviewed journal

Locations

US (1)