Back to resultsRapamycin - Effects on Alzheimer's and Cognitive Health (REACH)
Primary Purpose
Mild Cognitive Impairment, Alzheimer Disease
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rapamycin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Mild Cognitive Impairment focused on measuring Cognition, Alzheimer's disease biomarkers, Neuroimaging
Eligibility Criteria
Inclusion Criteria:
- Both genders and all ethnic groups
- Ages 55 to 89 years
- 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)
- Amyloid positivity based on Amyloid PET Imaging
- 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
- 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
- Stable dose of AD medications (Donepezil, rivastigmine, Memantine, galantamine) for at least three months is allowed
Exclusion Criteria:
- Diabetes (HBA1c≥6.5% or antidiabetic 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 450 3A4 (CYP3A4)
- Immunosuppressant therapy within the last year
- Chemotherapy or radiation treatment within the last year
- Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities
- Untreated hypertriglyceridemia (fasting triglycerides < 250 mg/dl)
- Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%)
- Chronic heart failure
- Pregnancy or lactation
- Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
- Significant neurological conditions other than AD or MCI
- Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg - based on two readings)
- Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or severe mental illness
- 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
- Organ transplant recipients
Sites / Locations
- Glenn Biggs Institute for Alzheimer's & Neurodegenerative DiseasesRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
RAPA (rapamycin) treatment group
Placebo group
Arm Description
Subjects will receive active drug
Subjects will receive placebo
Outcomes
Primary Outcome Measures
Number of adverse events
Development or worsening of medical symptoms or problems
Change in glucose level
A comprehensive metabolic panel is used to measure change in glucose level
Change in albumin
A comprehensive metabolic panel is used to measure change in albumin level
Change in carbon dioxide or bicarbonate (CO2)
A comprehensive metabolic panel is used to measure change in CO2
Change in calcium
A comprehensive metabolic panel is used to measure change in calcium levels
Secondary Outcome Measures
Central nervous system penetration of rapamycin
A lumbar puncture and blood draw will be used to evaluate levels of study drug
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.
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.
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.
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.
Change in Gait Speed
Gait speed will be evaluated with an electronic gait mat
Change in Grip Strength
Grip strength will be evaluated with a hand dynamometer
Change in CSF amyloid beta
Cerebrospinal fluid (CSF) levels of amyloid beta
Change in cerebral glucose metabolism
Cerebral glucose metabolism is measured using fluorodeoxyglucose-Positron emission tomography (FDG-PET)
Change in Brain Volumetry
Measure of brain volumetry using MRI
Full Information
NCT ID
NCT04629495
First Posted
November 9, 2020
Last Updated
October 18, 2023
Sponsor
The University of Texas Health Science Center at San Antonio
1. Study Identification
Unique Protocol Identification Number
NCT04629495
Brief Title
Rapamycin - Effects on Alzheimer's and Cognitive Health
Acronym
REACH
Official Title
Rapamycin - Effects on Alzheimer's and Cognitive Health (REACH)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 11, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment, Alzheimer Disease
Keywords
Cognition, Alzheimer's disease biomarkers, Neuroimaging
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
placebo controlled study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Quadruple-blind
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RAPA (rapamycin) treatment group
Arm Type
Active Comparator
Arm Description
Subjects will receive active drug
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
Subjects will receive placebo
Intervention Type
Drug
Intervention Name(s)
Rapamycin
Other Intervention Name(s)
Sirolimus, RAPA
Intervention Description
RAPA will be administered orally 1mg daily
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo capsule
Intervention Description
Placebo will be administered orally once daily
Primary Outcome Measure Information:
Title
Number of adverse events
Description
Development or worsening of medical symptoms or problems
Time Frame
Baseline to 12 months
Title
Change in glucose level
Description
A comprehensive metabolic panel is used to measure change in glucose level
Time Frame
Baseline to 12 months
Title
Change in albumin
Description
A comprehensive metabolic panel is used to measure change in albumin level
Time Frame
Baseline to 12 months
Title
Change in carbon dioxide or bicarbonate (CO2)
Description
A comprehensive metabolic panel is used to measure change in CO2
Time Frame
Baseline to 12 months
Title
Change in calcium
Description
A comprehensive metabolic panel is used to measure change in calcium levels
Time Frame
Baseline to 12 months
Secondary Outcome Measure Information:
Title
Central nervous system penetration of rapamycin
Description
A lumbar puncture and blood draw will be used to evaluate levels of study drug
Time Frame
Baseline and 12 months
Title
Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5)
Description
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.
Time Frame
Baseline to 12 months
Title
Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB)
Description
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.
Time Frame
Baseline to 12 months
Title
Change in Functional status
Description
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.
Time Frame
Baseline to 12 months
Title
Change in Neuropsychiatric symptoms
Description
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.
Time Frame
Baseline to 12 months
Title
Change in Gait Speed
Description
Gait speed will be evaluated with an electronic gait mat
Time Frame
Baseline to 12 months
Title
Change in Grip Strength
Description
Grip strength will be evaluated with a hand dynamometer
Time Frame
Baseline to 12 months
Title
Change in CSF amyloid beta
Description
Cerebrospinal fluid (CSF) levels of amyloid beta
Time Frame
Baseline to 12 months
Title
Change in cerebral glucose metabolism
Description
Cerebral glucose metabolism is measured using fluorodeoxyglucose-Positron emission tomography (FDG-PET)
Time Frame
Baseline to 12 months
Title
Change in Brain Volumetry
Description
Measure of brain volumetry using MRI
Time Frame
Baseline to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Both genders and all ethnic groups
Ages 55 to 89 years
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)
Amyloid positivity based on Amyloid PET Imaging
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
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
Stable dose of AD medications (Donepezil, rivastigmine, Memantine, galantamine) for at least three months is allowed
Exclusion Criteria:
Diabetes (HBA1c≥6.5% or antidiabetic 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 450 3A4 (CYP3A4)
Immunosuppressant therapy within the last year
Chemotherapy or radiation treatment within the last year
Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities
Untreated hypertriglyceridemia (fasting triglycerides < 250 mg/dl)
Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%)
Chronic heart failure
Pregnancy or lactation
Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
Significant neurological conditions other than AD or MCI
Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg - based on two readings)
Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or severe mental illness
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
Organ transplant recipients
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mitzi Gonzales, Phd
Phone
210-450-9047
Email
gonzalesm20@uthscsa.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Floyd A Jones
Phone
210-450-3158
Email
jonesfa@uthscsa.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sudha J Seshadri, MD
Organizational Affiliation
UT Health San Antonio
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mitzi J Gonzales, PhD
Organizational Affiliation
UT Health San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mitzi Gonzales, PhD
Phone
210-450-9047
Email
gonzalesm20@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
Floyd A Jones
Phone
(210) 450-3518
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All IPD that underlie results in a publication
IPD Sharing Time Frame
At study completion
IPD Sharing Access Criteria
Through journal publication
Learn more about this trial
Rapamycin - Effects on Alzheimer's and Cognitive Health
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