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

Primary Purpose

Cognitive Impairment, Mild, Alzheimer Disease

Status

Active

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Rapamune

About this trial

This is an interventional treatment trial for Cognitive Impairment, Mild

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

UTHSA McDermott Clinical Sciences Building

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAPA intervention

Arm Description

Sirolimus 1mg orally once a day for 8 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Adverse Events

Number of adverse events experienced across all 10 subjects after they were enrolled and randomized to treatment, regardless of relatedness to intervention.

Change in CSF A Beta-42 Levels From Baseline to 8 Weeks

Evaluation of relevant AD biomarkers.Change is calculated as value at 8 weeks minus the value at baseline.

Electronic Gait Mapping

Assessment of physical functioning under single and dual task conditions

Grip Strength

Assessment of physical function using grip strength

Clinical Dementia Rating (CDR) Global Score

A 5 point scale used to characterize six domains of cognitive and functional performance to give a possible score of 0-18. Each domain is rated on a score of 0 to 3 (0, 0.5, 1, 2 or 3) and the global score is derived based on the Washington University logarithm. Higher scores indicate worse cognitive and functional status.

Benson Figure Copy

A scale used to score a test of visuoconstructional abilities. Scores range from 0-16 with higher scores indicating better performance. Change is calculated as performance at 8 weeks minus baseline.

Neuropsychiatric Inventory (NPI)

A scale to assess dementia-related behavioral symptoms. The score represents the sum of 12 items, each scored 0-3. The total score can range from 0 to 36. Higher scores indicated greater neuropsychiatric severity. Change is calculated as the 8-week score minus baseline.

Functional Activities Questionnaire (FAQ)

An informant rates the subject's ability using a scoring system. The measure consists of 10 items with scoring ranging from 0-3 and the total score represents the sum of the items. The scores range from 0 to 30 with higher scores indicating more functional impairment. Change is calculated as the 8-week score minus baseline.

Full Information

NCT ID

NCT04200911

First Posted

December 6, 2019

Last Updated

March 20, 2023

Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

National Center for Advancing Translational Sciences (NCATS)

1. Study Identification

Unique Protocol Identification Number

NCT04200911

Brief Title

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

Acronym

CARPE_DIEM

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 1, 2020 (Actual)

Primary Completion Date

January 13, 2022 (Actual)

Study Completion Date

January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

National Center for Advancing Translational Sciences (NCATS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cognitive Impairment, Mild, Alzheimer Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RAPA intervention

Arm Type

Experimental

Arm Description

Sirolimus 1mg orally once a day for 8 weeks

Intervention Type

Drug

Intervention Name(s)

Rapamune

Other Intervention Name(s)

Sirolimus

Intervention Description

Sirolimus 1mg capsules

Primary Outcome Measure Information:

Title

Blood Brain Barrier Penetration of RAPA

Description

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.

Time Frame

Change from Baseline to 8 weeks

Secondary Outcome Measure Information:

Title

Adverse Events

Description

Number of adverse events experienced across all 10 subjects after they were enrolled and randomized to treatment, regardless of relatedness to intervention.

Time Frame

Baseline to 8 weeks

Title

Change in CSF A Beta-42 Levels From Baseline to 8 Weeks

Description

Evaluation of relevant AD biomarkers.Change is calculated as value at 8 weeks minus the value at baseline.

Time Frame

Baseline to 8 weeks

Title

Electronic Gait Mapping

Description

Assessment of physical functioning under single and dual task conditions

Time Frame

Change from Baseline to 8 weeks

Title

Grip Strength

Description

Assessment of physical function using grip strength

Time Frame

Change from Baseline to 8 weeks

Title

Clinical Dementia Rating (CDR) Global Score

Description

Time Frame

Change from Baseline to 8 weeks

Title

Benson Figure Copy

Description

A scale used to score a test of visuoconstructional abilities. Scores range from 0-16 with higher scores indicating better performance. Change is calculated as performance at 8 weeks minus baseline.

Time Frame

Change from Baseline to 8 weeks

Title

Neuropsychiatric Inventory (NPI)

Description

Time Frame

Change from Baseline to 8 weeks

Title

Functional Activities Questionnaire (FAQ)

Description

Time Frame

Change from Baseline to 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mitzi Gonzales, PhD

Organizational Affiliation

UT Health San Antonio

Official's Role

Principal Investigator

Facility Information:

Facility Name

UTHSA McDermott Clinical Sciences Building

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The Institution, Sponsor or respective designees may review results prior to presenting or publishing the results of a scientific investigation involving this Study in accordance with ICJME guidelines and institutional requirements.

IPD Sharing Time Frame

After publication in a peer reviewed journal

Learn more about this trial

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

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