NCT04200911CompletedEarly Phase 1
Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway (CARPE DIEM)
The University of Texas Health Science Center at San Antonio1 site in 1 country10 target enrollmentStarted: June 1, 2020Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Completed
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Blood Brain Barrier Penetration of RAPA
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 55 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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
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; 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
- •Poorly controlled blood pressure (systolic BP>160, diastolic BP>90mmHg)
- •Active inflammatory, COVID-19, 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
- •Organ transplant recipients
Arms & Interventions
RAPA intervention
Experimental
Sirolimus 1mg orally once a day for 8 weeks
Intervention: Rapamune (Drug)
Outcomes
Primary Outcomes
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. Change is calculated as value at 8 weeks minus the value at baseline.
Secondary Outcomes
- 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)
- Change in CSF Inflammatory Markers From Baseline to 8 Weeks(Baseline to 8 weeks)
- Change in Plasma Inflammatory Markers From Baseline to 8 Weeks(Baseline to 8 weeks)
- Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks(Baseline to 8 weeks)
- Safety Labs - Change in Red Blood Cell Count(Baseline to 8 weeks)
- Safety Labs - Change in Mean Corpuscular Volume(8 weeks)
- Safety Labs - Change in Mean Corpuscular Hemoglobin(8-weeks)
- Safety Labs - Change in Metabolic Parameters (g/dl)(8 weeks)
- Safety Labs - Change in Hematocrit(8 weeks)
- Safety Labs - Change in Monocytes(8 weeks)
- Safety Labs - Change in Red Cell Distribution Width(8 weeks)
- Safety Labs - Change in Hemoglobin A1c(8 weeks)
- Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl)(8 weeks)
- Safety Labs - Change in Sodium and Potassium (mmol/L)(8 weeks)
- Safety Labs - Change in Liver Panel (iU/L)(8 weeks)
- Cognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)(8 weeks)
- Cognition/Functional Status - Change on the Clinical Rating Scale Global Score(8 weeks)
- Cognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score(8 weeks)
- Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall(8 weeks)
- Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall(8 weeks)
- Cognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim(8 weeks)
- Cognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim(8 weeks)
- Cognition/Functional Status - Change on the Benson Figure Copy(8 weeks)
- Cognition/Functional Status - Change on the Benson Figure Delayed Recall(8 weeks)
- Cognition/Functional Status - Change on the Number Span Forward(8 weeks)
- Cognition/Functional Status - Change on the Number Span Backward(8 weeks)
- Cognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion(8 weeks)
- Cognition/Functional Status - Change Trail Making Test Part B, Time to Completion(8 weeks)
- Cognition/Functional Status - Change on Phonemic Fluency(8 weeks)
- Cognition/Functional Status - Change on Semantic Fluency(8 weeks)
- Cognition/Functional Status - Change on the Multilingual Naming Test(8 weeks)
- Cognition/Functional Status - Change on the Hayling, Total Errors(8 weeks)
- Cognition/Functional Status - Change on Grip Strength, Dominant Hand(8 weeks)
- Cognition/Functional Status - Change on Grip Strength, Non-dominant Hand(8 weeks)
- Cognition/Functional Status - Change on the Geriatric Depression Scale 15-item(8 weeks)
- Cognition/Functional Status - Change on the Functional Activities Questionnaire(8 weeks)
- Cognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire(8 weeks)
Investigators
Study Sites (1)
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