(CARPE DIEM): Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway
Study Details
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 |
|---|---|---|
| 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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: RAPA intervention Sirolimus 1mg orally once a day for 8 weeks |
Drug: Rapamune
Sirolimus 1mg capsules
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Blood brain barrier penetration of RAPA [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
- Adverse events [Baseline to 8 weeks]
Number of adverse events experienced
- Target engagement of RAPA treatment in Alzheimer's Disease (AD) [Baseline and 8 weeks]
Evaluation of relevant AD biomarkers
- Mini-Mental State Exam (MMSE) [Change from Baseline to 8 weeks]
A 30 point questionnaire used to measure cognitive impairment
- Alzheimer's Disease Assessment Scale (ADAS-Cog) Word list Immediate and Delayed [Change from Baseline to 8 weeks]
A scale used to assess progression of Alzheimer's Disease
- Electronic Gait Mapping [Change from Baseline to 8 weeks]
Assessment of physical functioning under single and dual task conditions
- Grip Strength [Change from Baseline to 8 weeks]
Assessment of physical function using grip strength
- Clinical Dementia Rating (CDR) [Change from Baseline to 8 weeks]
A 5 point scale used to characcterize six domains of cognitive an functional performance
- Benson Figure Copy [Change from Baseline to 8 weeks]
A scale used to test memory recall
- Tablet-Based Cognitive Assessment (TabCat) [Change from Baseline to 8 weeks]
A scale used to score cognitive assessment based on a number of assigned tasks
- Global Deterioration Scale [Change from Baseline to 8 weeks]
A caregiver assessment of the stage of AD progression from Stage 1-7
- Neuropsychiatric Inventory (NPI) [Change from Baseline to 8 weeks]
A scale to assess dementia-related behavioral symptoms
- Functional activities questionnaire (FAQ) [Change from Baseline to 8 weeks]
An informant rates the subject's ability using a scoring system
- Pittsburgh Sleep Quality Index (PSQI) [Change from baseline to 8 weeks]
A questionnaire used to assess sleep quality
Eligibility Criteria
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
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Current tobacco or illicit drug use or alcohol abuse
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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
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Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%)
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Chronic heart failure
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Pregnancy
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Recent history (past 6 months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
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significant neurological conditions other than AD
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Poorly controlled blood pressure (systolic BP>160, diastolic BP>90mmHg)
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Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or psychiatric disease
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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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HSC20190850H