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

Alzheimer Disease Clinical Trial

— CARPE_DIEM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04200911
• Other study ID #: HSC20190850H
• Secondary ID: UL1TR002645
• Status: Completed
• Phase: Early Phase 1
• Start date: June 1, 2020
• Est. completion date: January 13, 2022

Study information

• Verified date: December 2023
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 13, 2022
• Est. primary completion date: January 13, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Cognitive Impairment, Mild

Intervention

Drug:
• Rapamune
Sirolimus 1mg capsules

Locations

Country	Name	City	State
United States	UTHSA McDermott Clinical Sciences Building	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	National Center for Advancing Translational Sciences (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse Events	Number of adverse events experienced across all 10 subjects after they were enrolled and randomized to treatment, regardless of relatedness to intervention.	Baseline to 8 weeks
Secondary	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.	Baseline to 8 weeks
Secondary	Electronic Gait Mapping	Assessment of physical functioning under single and dual task conditions	Change from Baseline to 8 weeks
Secondary	Grip Strength	Assessment of physical function using grip strength	Change from Baseline to 8 weeks
Secondary	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.	Change from Baseline to 8 weeks
Secondary	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.	Change from Baseline to 8 weeks
Secondary	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.	Change from Baseline to 8 weeks
Secondary	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.	Change from Baseline to 8 weeks