Effect of Rapamycin to Improve Cardiac Function in Frail Older Adults

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT04996719

Collaborator

(none)

Enrollment

Location

Arm

6.3

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: Rapamune	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 24, 2022

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rapamycin find safe doses for patients who have heart failure with preserved ejection fraction	Drug: Rapamune 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). Other Names: Rapamycin

Arm

Intervention/Treatment

Experimental: Rapamycin

find safe doses for patients who have heart failure with preserved ejection fraction

Drug: Rapamune

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).

Other Names:

Rapamycin

Outcome Measures

Primary Outcome Measures

Change cardiopulmonary reserve capacity by improving peak VO2 with rapamycin [6 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator: Mandeep Singh, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Mayo Clinic Clinical Trials

Publications

None provided.

Responsible Party:

Mandeep Singh, Professor of Medicine, Mayo Clinic

ClinicalTrials.gov Identifier:

NCT04996719

Other Study ID Numbers:

21-003837

First Posted:

Aug 9, 2021

Last Update Posted:

Jun 30, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Heart Failure

Sirolimus

Study Results

No Results Posted as of Jun 30, 2022