Back to resultsEffect of Rapamycin to Improve Cardiac Function in Frail Older Adults
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rapamune
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure
Eligibility Criteria
Inclusion Criteria:
- Age ≥60 years
- Diagnosis of HFpEF by either H2FEPF score of 6-9 or HFA-PEFF score of 5-6, or invasively confirmed diagnosis of HFpEF (resting pulmonary capillary wedge pressure ≥15mmHg or ≥25mmHg with exercise).
- Diagnosis of computable phenotype of frailty rests on screening questions about ability to climb two flights of stairs, activities of daily living, living environment, wearing of dentures/hearing aids, and whether the patient uses assistive devices.
Exclusion Criteria:
- Reduced ejection fraction (≤50%) with or without prior history of myocardial infarction
- Acute coronary syndrome <3 months
- Uncontrolled diabetes mellitus (HbA1C>8)
- Uncontrolled hypertension (>160/100mmHg, despite 3 antihypertensive medications)
- Nephrotic syndrome or eGFR <30mL/min/1.73m2
- Cirrhosis
- Hepatitis B/C positive
- Elevated lived enzymes (AST/ALT>3ULN
- Prior malignancy other than basal cell carcinoma
- History of ongoing, chronic or recurrent infectious disease
- Suspected/proven immunocompromised state
- Uncontrolled hyperlipidemia (fasting TG >400 mg/dL (>4.5 mmol/L) or total cholesterol >300 mg/dL (>7.8 mmol/L) despite maximum lipid lowering therapy
- Class IV HF symptoms
Sites / Locations
- Mayo Clinic Rochester
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rapamycin
Arm Description
find safe doses for patients who have heart failure with preserved ejection fraction
Outcomes
Primary Outcome Measures
Change cardiopulmonary reserve capacity by improving peak VO2 with rapamycin
In this pilot, proof-of-concept study, we hypothesize that in older adults (≥60 years) with HFpEF who are frail, chronic rapamycin administration will change their cardiopulmonary reserve capacity by improving peak VO2.Primary safety objective is the safety of rapamycin.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04996719
Brief Title
Effect of Rapamycin to Improve Cardiac Function in Frail Older Adults
Official Title
Effect of Rapamycin to Improve Cardiac Function in Frail Older Adults With Heart Failure With Preserved Ejection Fraction: A Randomized Pilot and Proof-of-Concept Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 24, 2022 (Actual)
Primary Completion Date
August 25, 2023 (Actual)
Study Completion Date
August 25, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this research is to see if the drug rapamycin will improve the heart's ability to pump by improving your oxygen consumption.
Detailed Description
This will be a pilot, proof-of-concept study. Patients 60 years or older with invasively proven HFpEF or have definite HFpEF as determined by the 2 established scores and frailty (positive screen for computable phenotype), will be approached for enrollment. Subjects meeting screening criteria following written informed consent will be randomized to receive rapamycin or matching placebo (study drug). Efficacy outcomes will be measured at baseline and at 6 months. Safety will be assessed by in person or remote video monitoring weekly for 1 month, then monthly for 5 months till the end of the study. We will also measure trough rapamycin levels (≤4ng/mL) twice-a-month for the first month and then monthly for 5 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rapamycin
Arm Type
Experimental
Arm Description
find safe doses for patients who have heart failure with preserved ejection fraction
Intervention Type
Drug
Intervention Name(s)
Rapamune
Other Intervention Name(s)
Rapamycin
Intervention Description
We will start the dose at 0.5mg capsule every other day for 2 weeks. If participants tolerate this dose and trough blood levels are (≤4ng/mL), the dose of rapamycin will be increased to 0.5mg daily for the duration of the study. If necessary, dose can remain at 0.5 mg every other day, depending on the trough level. To avoid immunosuppression, we will target lower dose of rapamycin, maintain lower trough serum levels (≤4ng/mL).
Primary Outcome Measure Information:
Title
Change cardiopulmonary reserve capacity by improving peak VO2 with rapamycin
Description
In this pilot, proof-of-concept study, we hypothesize that in older adults (≥60 years) with HFpEF who are frail, chronic rapamycin administration will change their cardiopulmonary reserve capacity by improving peak VO2.Primary safety objective is the safety of rapamycin.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥60 years
Diagnosis of HFpEF by either H2FEPF score of 6-9 or HFA-PEFF score of 5-6, or invasively confirmed diagnosis of HFpEF (resting pulmonary capillary wedge pressure ≥15mmHg or ≥25mmHg with exercise).
Diagnosis of computable phenotype of frailty rests on screening questions about ability to climb two flights of stairs, activities of daily living, living environment, wearing of dentures/hearing aids, and whether the patient uses assistive devices.
Exclusion Criteria:
Reduced ejection fraction (≤50%) with or without prior history of myocardial infarction
Acute coronary syndrome <3 months
Uncontrolled diabetes mellitus (HbA1C>8)
Uncontrolled hypertension (>160/100mmHg, despite 3 antihypertensive medications)
Nephrotic syndrome or eGFR <30mL/min/1.73m2
Cirrhosis
Hepatitis B/C positive
Elevated lived enzymes (AST/ALT>3ULN
Prior malignancy other than basal cell carcinoma
History of ongoing, chronic or recurrent infectious disease
Suspected/proven immunocompromised state
Uncontrolled hyperlipidemia (fasting TG >400 mg/dL (>4.5 mmol/L) or total cholesterol >300 mg/dL (>7.8 mmol/L) despite maximum lipid lowering therapy
Class IV HF symptoms
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mandeep Singh, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Effect of Rapamycin to Improve Cardiac Function in Frail Older Adults
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