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

• ClinicalTrials.gov Identifier: NCT04629495
• Recruitment Status: Recruiting
• First Posted: November 16, 2020
• Last Update Posted: January 22, 2024
• Sponsor: The University of Texas Health Science Center at San Antonio
• Information provided by (Responsible Party): The University of Texas Health Science Center at San Antonio

Study Description

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.

Study Design

• 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: June 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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

Contacts and Locations

Contacts

Contact: Sudha Seshadri, MD; 210-450-8437; seshadri@uthscsa.edu

Contact: Floyd A Jones; 210-450-3158; jonesfa@uthscsa.edu

Locations

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

• Principal Investigator: Sudha J Seshadri, MD; UT Health San Antonio
• Principal Investigator: Mitzi J Gonzales, PhD; UT Health San Antonio

More Information

• Responsible Party: The University of Texas Health Science Center at San Antonio
• ClinicalTrials.gov Identifier: NCT04629495
• Other Study ID Numbers: HSC20200763H
• First Posted: November 16, 2020
• Last Update Posted: January 22, 2024
• Last Verified: January 2024

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The University of Texas Health Science Center at San Antonio:

Cognition; Alzheimer's disease biomarkers; Neuroimaging

Additional relevant MeSH terms:

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