Clinical trial NCT04200911: Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway
Official title: Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway (CARPE DIEM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Cognitive Impairment, Mild
Alzheimer Disease
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2019-12-16
Enrollment: 10
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Blood Brain Barrier Penetration of RAPA
timeFrame: Change from Baseline to 8 weeks
Secondary outcomes:
measure: Adverse Events
timeFrame: Baseline to 8 weeks
measure: Change in Vitals From Baseline to 8 Weeks
timeFrame: Baseline to 8 weeks
measure: Percentage of Study Drug Pills Taken
timeFrame: Baseline to 8 weeks
measure: Change in CSF AD Biomarkers From Baseline to 8 Weeks
timeFrame: Baseline to 8 weeks
measure: Change in Plasma AD Biomarkers From Baseline to 8 Weeks
timeFrame: Baseline to 8 weeks
measure: Change in CSF Inflammatory Markers From Baseline to 8 Weeks
timeFrame: Baseline to 8 weeks
measure: Change in Plasma Inflammatory Markers From Baseline to 8 Weeks
timeFrame: Baseline to 8 weeks
measure: Safety Labs - Change in White Blood Cell and Platelet Counts From Baseline to 8 Weeks
timeFrame: Baseline to 8 weeks
measure: Safety Labs - Change in Red Blood Cell Count
timeFrame: Baseline to 8 weeks
measure: Safety Labs - Change in Mean Corpuscular Volume
timeFrame: 8 weeks
measure: Safety Labs - Change in Mean Corpuscular Hemoglobin
timeFrame: 8-weeks
measure: Safety Labs - Change in Metabolic Parameters (g/dl)
timeFrame: 8 weeks
measure: Safety Labs - Change in Hematocrit
timeFrame: 8 weeks
measure: Safety Labs - Change in Monocytes
timeFrame: 8 weeks
measure: Safety Labs - Change in Red Cell Distribution Width
timeFrame: 8 weeks
measure: Safety Labs - Change in Hemoglobin A1c
timeFrame: 8 weeks
measure: Safety Labs - Change in Metabolic and Lipid Parameters (mg/dl)
timeFrame: 8 weeks
measure: Safety Labs - Change in Sodium and Potassium (mmol/L)
timeFrame: 8 weeks
measure: Safety Labs - Change in Liver Panel (iU/L)
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change in Montreal Cognitive Assessment (MoCA)
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Clinical Rating Scale Global Score
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Clinical Rating Scale Sum of Boxes Score
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Immediate Recall
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Hopkins Verbal Learning Test - Revised Delayed Recall
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Craft Story Immediate Recall Verbatim
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Craft Story Delayed Recall Verbatim
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Benson Figure Copy
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Benson Figure Delayed Recall
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Number Span Forward
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Number Span Backward
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Trail Making Test Part A, Time to Completion
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change Trail Making Test Part B, Time to Completion
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on Phonemic Fluency
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on Semantic Fluency
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Multilingual Naming Test
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Hayling, Total Errors
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on Grip Strength, Dominant Hand
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on Grip Strength, Non-dominant Hand
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Geriatric Depression Scale 15-item
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Functional Activities Questionnaire
timeFrame: 8 weeks
measure: Cognition/Functional Status - Change on the Neuropsychiatric Inventory Questionnaire
timeFrame: 8 weeks
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: UTHSA McDermott Clinical Sciences Building
state: Texas
Study officials:
affiliation: UT Health San Antonio
name: Mitzi Gonzales, PhD
role: PRINCIPAL_INVESTIGATOR
References: