Rapamycin - Effects on Alzheimer's and Cognitive Health

Alzheimer Disease Clinical Trial

— REACH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04629495
• Other study ID #: HSC20200763H
• Status: Recruiting
• Phase: Phase 2
• Start date: August 11, 2021
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: The University of Texas Health Science Center at San Antonio
• Contact: Sudha Seshadri, MD
• Phone: 210-450-8437
• Email: seshadri[@]uthscsa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Drug:
• Rapamycin
RAPA will be administered orally 1mg daily

Other:
• Placebo
Placebo will be administered orally once daily

Locations

Country	Name	City	State
United States	Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events	Development or worsening of medical symptoms or problems	Baseline to 12 months
Primary	Change in glucose level	A comprehensive metabolic panel is used to measure change in glucose level	Baseline to 12 months
Primary	Change in albumin	A comprehensive metabolic panel is used to measure change in albumin level	Baseline to 12 months
Primary	Change in carbon dioxide or bicarbonate (CO2)	A comprehensive metabolic panel is used to measure change in CO2	Baseline to 12 months
Primary	Change in calcium	A comprehensive metabolic panel is used to measure change in calcium levels	Baseline to 12 months
Secondary	Central nervous system penetration of rapamycin	A lumbar puncture and blood draw will be used to evaluate levels of study drug	Baseline and 12 months
Secondary	Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5)	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.	Baseline to 12 months
Secondary	Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB)	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.	Baseline to 12 months
Secondary	Change in Functional status	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.	Baseline to 12 months
Secondary	Change in Neuropsychiatric symptoms	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.	Baseline to 12 months
Secondary	Change in Gait Speed	Gait speed will be evaluated with an electronic gait mat	Baseline to 12 months
Secondary	Change in Grip Strength	Grip strength will be evaluated with a hand dynamometer	Baseline to 12 months
Secondary	Change in CSF amyloid beta	Cerebrospinal fluid (CSF) levels of amyloid beta	Baseline to 12 months
Secondary	Change in cerebral glucose metabolism	Cerebral glucose metabolism is measured using fluorodeoxyglucose-Positron emission tomography (FDG-PET)	Baseline to 12 months
Secondary	Change in Brain Volumetry	Measure of brain volumetry using MRI	Baseline to 12 months