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

• ClinicalTrials.gov Identifier: NCT04200911
• Recruitment Status: Active, not recruiting
• First Posted: December 16, 2019
• Last Update Posted: February 4, 2022
• Sponsor: The University of Texas Health Science Center at San Antonio
• Information provided by (Responsible Party): The University of Texas Health Science Center at San Antonio

Study Description

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

Condition or disease	Intervention/treatment	Phase
Cognitive Impairment, Mild; Alzheimer Disease	Drug: Rapamune	Early Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway (CARPE DIEM)
• Actual Study Start Date: June 1, 2020
• Actual Primary Completion Date: January 13, 2022
• Estimated Study Completion Date: January 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: RAPA intervention; Sirolimus 1mg orally once a day for 8 weeks	Drug: Rapamune; Sirolimus 1mg capsules; Other Name: Sirolimus

Outcome Measures

Primary Outcome Measures :

1. Blood brain barrier penetration of RAPA [ Time Frame: Change from Baseline to 8 weeks ]
   Lumbar punctures will be performed at baseline and after the final RAPA dose, to assess CSF levels of the drug.

Secondary Outcome Measures :

1. Adverse events [ Time Frame: Baseline to 8 weeks ]
   Number of adverse events experienced
2. Target engagement of RAPA treatment in Alzheimer's Disease (AD) [ Time Frame: Baseline and 8 weeks ]
   Evaluation of relevant AD biomarkers
3. Mini-Mental State Exam (MMSE) [ Time Frame: Change from Baseline to 8 weeks ]
   A 30 point questionnaire used to measure cognitive impairment
4. Alzheimer's Disease Assessment Scale (ADAS-Cog) Word list Immediate and Delayed [ Time Frame: Change from Baseline to 8 weeks ]
   A scale used to assess progression of Alzheimer's Disease
5. Electronic Gait Mapping [ Time Frame: Change from Baseline to 8 weeks ]
   Assessment of physical functioning under single and dual task conditions
6. Grip Strength [ Time Frame: Change from Baseline to 8 weeks ]
   Assessment of physical function using grip strength
7. Clinical Dementia Rating (CDR) [ Time Frame: Change from Baseline to 8 weeks ]
   A 5 point scale used to characcterize six domains of cognitive an functional performance
8. Benson Figure Copy [ Time Frame: Change from Baseline to 8 weeks ]
   A scale used to test memory recall
9. Tablet-Based Cognitive Assessment (TabCat) [ Time Frame: Change from Baseline to 8 weeks ]
   A scale used to score cognitive assessment based on a number of assigned tasks
10. Global Deterioration Scale [ Time Frame: Change from Baseline to 8 weeks ]
    A caregiver assessment of the stage of AD progression from Stage 1-7
11. Neuropsychiatric Inventory (NPI) [ Time Frame: Change from Baseline to 8 weeks ]
    A scale to assess dementia-related behavioral symptoms
12. Functional activities questionnaire (FAQ) [ Time Frame: Change from Baseline to 8 weeks ]
    An informant rates the subject's ability using a scoring system
13. Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Change from baseline to 8 weeks ]
    A questionnaire used to assess sleep quality

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Diagnosis of Mild Cognitive Impairment (MCI), Clinical Dementia Rating Scale (CDR)=0.5-1; Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall ≤5% based on age-adjusted normal values, clinician approved
• Normal blood cell counts without clinically significant excursions
• 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

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
• Immunosuppressant therapy within the last year
• Chemotherapy or radiation treatment within the last year
• Current or chronic history of liver disease or known hepatic or biliary abnormalities
• 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, 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

Contacts and Locations

Locations

United States, Texas

UTHSA McDermott Clinical Sciences Building

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

The University of Texas Health Science Center at San Antonio

Investigators

• Principal Investigator: Mitzi Gonzales, PhD; UT Health San Antonio

More Information

• Responsible Party: The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT04200911
• Other Study ID Numbers: HSC20190850H
• First Posted: December 16, 2019
• Last Update Posted: February 4, 2022
• Last Verified: February 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Sirolimus; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs