Mild Cognitive ImpairmentPhase 2REACHNCT04629495
Rapamycin - Effects on Alzheimer's and Cognitive Health
A Phase 2 study testing Rapamycin in people with Mild Cognitive Impairment and Alzheimer Disease, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 55 to 89 years
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Disease
- What is being tested?
- Rapamycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Aug 2021to 5 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases
San Antonio, Texas, 78229
About this study
Official title: Rapamycin - Effects on Alzheimer's and Cognitive Health (REACH)
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).
Read the 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.
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Being tested
- Rapamycin, Placebo
- Keywords
- Cognition, Alzheimer's disease biomarkers, Neuroimaging
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
Also called Sirolimus, RAPA
RAPA will be administered orally 1mg daily
PlaceboOther
Also called Placebo capsule
Placebo will be administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| RAPA (rapamycin) treatment group | Active comparator | Subjects will receive active drug Receives: Drug: Rapamycin |
| Placebo group | Placebo comparator | Subjects will receive placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events
Development or worsening of medical symptoms or problems
Measured: Baseline to 12 months
Change in glucose level
A comprehensive metabolic panel is used to measure change in glucose level
Measured: Baseline to 12 months
Change in albumin
A comprehensive metabolic panel is used to measure change in albumin level
Measured: Baseline to 12 months
Change in carbon dioxide or bicarbonate (CO2)
A comprehensive metabolic panel is used to measure change in CO2
Measured: Baseline to 12 months
Change in calcium
A comprehensive metabolic panel is used to measure change in calcium levels
Measured: Baseline to 12 months
Secondary outcomes (10)
Central nervous system penetration of rapamycin
A lumbar puncture and blood draw will be used to evaluate levels of study drug
Measured: Baseline and 12 months
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.
Measured: Baseline to 12 months
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.
Measured: Baseline to 12 months
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.
Measured: Baseline to 12 months
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.
Measured: Baseline to 12 months
Change in Gait Speed
Gait speed will be evaluated with an electronic gait mat
Measured: Baseline to 12 months
Change in Grip Strength
Grip strength will be evaluated with a hand dynamometer
Measured: Baseline to 12 months
Change in CSF amyloid beta
Cerebrospinal fluid (CSF) levels of amyloid beta
Measured: Baseline to 12 months
Change in cerebral glucose metabolism
Cerebral glucose metabolism is measured using fluorodeoxyglucose-Positron emission tomography (FDG-PET)
Measured: Baseline to 12 months
Change in Brain Volumetry
Measure of brain volumetry using MRI
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2020
- Study start11 Aug 2021
- Primary completion5 Mar 2026
- Study completion5 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- placebo controlled study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Alzheimer's Association
- Responsible party
- Sponsor
- Investigators
- Sudha J Seshadri, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04629495
- Sponsor's protocol ID
- HSC20200763H
- Acronym
- REACH
- Status last verified
- Jun 2026
- First submitted
- 9 Nov 2020
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapamycin - Effects on Alzheimer's and Cognitive Health (REACH)
- ClinicalTrials.gov ID
- NCT04629495
- Acronym / sponsor ID
- REACH / HSC20200763H
- Conditions
- Mild Cognitive Impairment, Alzheimer Disease
- Keywords
- Cognition, Alzheimer's disease biomarkers, Neuroimaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- Alzheimer's Association
- Study start
- 11 Aug 2021 (actual)
- Primary completion
- 5 Mar 2026 (actual)
- Study completion
- 5 Mar 2027 (estimated)
- First posted
- 16 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- placebo controlled study
| Arm | Type | Receives |
|---|---|---|
| RAPA (rapamycin) treatment group | Active comparator | Drug: RapamycinSubjects will receive active drug |
| Placebo group | Placebo comparator | Other: PlaceboSubjects will receive placebo |
Who may qualify
- Ages
- 55 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RapamycinAlso: Sirolimus, RAPARAPA will be administered orally 1mg daily | Drug | RAPA (rapamycin) treatment group |
| PlaceboAlso: Placebo capsulePlacebo will be administered orally once daily | Other | Placebo group |
Primary outcome
Number of adverse events
Time frame: Baseline to 12 months
Development or worsening of medical symptoms or problems
Change in glucose level
Time frame: Baseline to 12 months
A comprehensive metabolic panel is used to measure change in glucose level
Change in albumin
Time frame: Baseline to 12 months
A comprehensive metabolic panel is used to measure change in albumin level
Change in carbon dioxide or bicarbonate (CO2)
Time frame: Baseline to 12 months
A comprehensive metabolic panel is used to measure change in CO2
Change in calcium
Time frame: Baseline to 12 months
A comprehensive metabolic panel is used to measure change in calcium levels
10 secondary outcomes
Central nervous system penetration of rapamycin
Time frame: Baseline and 12 months
Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5)
Time frame: Baseline to 12 months
Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB)
Time frame: Baseline to 12 months
Change in Functional status
Time frame: Baseline to 12 months
Change in Neuropsychiatric symptoms
Time frame: Baseline to 12 months
Change in Gait Speed
Time frame: Baseline to 12 months
Change in Grip Strength
Time frame: Baseline to 12 months
Change in CSF amyloid beta
Time frame: Baseline to 12 months
Change in cerebral glucose metabolism
Time frame: Baseline to 12 months
Change in Brain Volumetry
Time frame: Baseline to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sudha J Seshadri, MD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rapamycin in people with Mild Cognitive Impairment and Alzheimer Disease, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events (time frame: Baseline to 12 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.