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Rapamycin - Effects on Alzheimer's and Cognitive Health (REACH)

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ClinicalTrials.gov Identifier: NCT04629495
Recruitment Status : Recruiting
First Posted : November 16, 2020
Last Update Posted : September 17, 2021
Sponsor:
Information provided by (Responsible Party):
Mitzi Gonzales, PhD, The University of Texas Health Science Center at San Antonio

Brief Summary:
This study will evaluate the safety, tolerability, and feasibility of 12 month oral rapamycin treatment in older adults with amnestic mild cognitive impairment (aMCI) and early stage Alzheimer's disease (AD).

Condition or disease Intervention/treatment Phase
Mild Cognitive Impairment Alzheimer Disease Drug: Rapamycin Other: Placebo Phase 2

Detailed Description:
The study will consist of a screening/baseline period of up to 90 days pre-study drug, with a 12-month (+3 day) treatment period with rapamycin, followed by a post-treatment assessment completed within 14 days of the final study drug dose, and a final assessment conducted 6-months (+14 days) after the final study drug dose. The study duration is not expected to exceed 90 weeks for participants.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: placebo controlled study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Quadruple-blind
Primary Purpose: Treatment
Official Title: Rapamycin - Effects on Alzheimer's and Cognitive Health (REACH)
Actual Study Start Date : August 11, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : August 2024


Arm Intervention/treatment
Active Comparator: RAPA (rapamycin) treatment group
Subjects will receive active drug
Drug: Rapamycin
RAPA will be administered orally 1mg daily
Other Name: Sirolimus, RAPA

Placebo Comparator: Placebo group
Subjects will receive placebo
Other: Placebo
Placebo will be administered orally once daily
Other Name: Placebo capsule




Primary Outcome Measures :
  1. Number of adverse events [ Time Frame: Baseline to 12 months ]
    Development or worsening of medical symptoms or problems

  2. Change in glucose level [ Time Frame: Baseline to 12 months ]
    A comprehensive metabolic panel is used to measure change in glucose level

  3. Change in albumin [ Time Frame: Baseline to 12 months ]
    A comprehensive metabolic panel is used to measure change in albumin level

  4. Change in carbon dioxide or bicarbonate (CO2) [ Time Frame: Baseline to 12 months ]
    A comprehensive metabolic panel is used to measure change in CO2

  5. Change in calcium [ Time Frame: Baseline to 12 months ]
    A comprehensive metabolic panel is used to measure change in calcium levels


Secondary Outcome Measures :
  1. Central nervous system penetration of rapamycin [ Time Frame: Baseline and 12 months ]
    A lumbar puncture and blood draw will be used to evaluate levels of study drug

  2. Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5) [ Time Frame: Baseline to 12 months ]
    Cognition will be measured using the PACC5 scale. The PACC5 is a composite score comprised of measures of global cognition, memory, and executive function. The score reflects an averaged z-score. Scores range from -3 to +3 with higher scores indicating better cognitive performance.

  3. Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB) [ Time Frame: Baseline to 12 months ]
    CDR is obtained through semistructured interviews of patients and informants, and cognitive functioning is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. Domain scores are entered into an online algorithm and CDR-SOB score obtained by summing each of the domain box scores, ranging from 0 to 18. A lower score indicates better cognition.

  4. Change in Functional status [ Time Frame: Baseline to 12 months ]
    Functional status will be measured using the functional assessment scale (FAS). The FAS is completed by a collateral source and assesses ability to complete instrumental activities of daily living. The scale has 10-items and responses range from 0-3. The total score is a sum of the individual items. The total score ranges from 0 to 30 with higher scores indicating more assistance needed.

  5. Change in Neuropsychiatric symptoms [ Time Frame: Baseline to 12 months ]
    Symptoms will be evaluated using the Geriatric Depression Scale 15 Item (GDS-15). The GDS-15 is a self-report questionnaire with 15 items that have response options of 0 or 1. The total score is the sum of the individual items. The total score on the measure ranges between 0 to 15 with higher scores indicating more depressive symptoms.

  6. Change in Gait Speed [ Time Frame: Baseline to 12 months ]
    Gait speed will be evaluated with an electronic gait mat

  7. Change in Grip Strength [ Time Frame: Baseline to 12 months ]
    Grip strength will be evaluated with a hand dynamometer

  8. Change in CSF amyloid beta [ Time Frame: Baseline to 12 months ]
    Cerebrospinal fluid (CSF) levels of amyloid beta

  9. Change in cerebral glucose metabolism [ Time Frame: Baseline to 12 months ]
    Cerebral glucose metabolism is measured using fluorodeoxyglucose-Positron emission tomography (FDG-PET)

  10. Change in Brain Volumetry [ Time Frame: Baseline to 12 months ]
    Measure of brain volumetry using MRI



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Both genders and all ethnic groups
  2. Ages 55 to 89 years
  3. Diagnosis of MCI or AD (Mini Mental Status Examination (MMSE): 18-30; Clinical Dementia Rating Scale (CDR) = 0.5 - 1; California Verbal Learning Test III (CVLT-III) Delayed Recall ≤16% based on age-adjusted norms, clinician approval)
  4. Amyloid positivity based on Amyloid PET Imaging
  5. Labs: Normal blood cell counts without clinically significant excursions; normal liver and renal function; and glucose control (HbA1c < 6.5%). Fasting lipid panel and prothrombin time/prothrombin time test/international normalized ration (PT/PTT/INR) within normal limits
  6. A legally authorized representative (LAR) designated to sign informed consent (if necessary) must attend the Screening visit and accompany the participant to all remaining visits to provide reported outcomes
  7. Stable dose of AD medications (Donepezil, rivastigmine, Memantine, galantamine) for at least three months is allowed

Exclusion Criteria:

  1. Diabetes (HBA1c≥6.5% or antidiabetic medications)
  2. History of skin ulcers or poor wound healing
  3. Current tobacco or illicit drug use or alcohol abuse
  4. Use of anti-platelet or anti-coagulant medications other than aspirin
  5. Current medications that affect cytochrome 450 3A4 (CYP3A4)
  6. Immunosuppressant therapy within the last year
  7. Chemotherapy or radiation treatment within the last year
  8. Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities
  9. Untreated hypertriglyceridemia (fasting triglycerides < 250 mg/dl)
  10. Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%)
  11. Chronic heart failure
  12. Pregnancy or lactation
  13. Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
  14. Significant neurological conditions other than AD or MCI
  15. Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg - based on two readings)
  16. Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or severe mental illness
  17. History of, or MRI, or CT positive for, any space occupying lesion, including mass effect or abnormal intracranial pressure, which would indicate contraindications to lumbar puncture
  18. Organ transplant recipients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04629495


Contacts
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Contact: Mitzi Gonzales, Phd 210-450-9047 gonzalesm20@uthscsa.edu
Contact: Floyd A Jones 210-450-3158 jonesfa@uthscsa.edu

Locations
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United States, Texas
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases Recruiting
San Antonio, Texas, United States, 78229
Contact: Mitzi Gonzales, PhD    210-450-9047    gonzalesm20@uthscsa.edu   
Contact: Floyd A Jones    (210) 450-3518      
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Investigators
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Principal Investigator: Sudha J Seshadri, MD UT Health San Antonio
Principal Investigator: Mitzi J Gonzales, PhD UT Health San Antonio
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Responsible Party: Mitzi Gonzales, PhD, Assistant Professor, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT04629495    
Other Study ID Numbers: HSC20200763H
First Posted: November 16, 2020    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results in a publication
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: At study completion
Access Criteria: Through journal publication

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mitzi Gonzales, PhD, The University of Texas Health Science Center at San Antonio:
Cognition
Alzheimer's disease biomarkers
Neuroimaging
Additional relevant MeSH terms:
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Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs