Effect of Rapamycin to Improve Cardiac Function in Frail Older Adults

Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04996719
• Other study ID #: 21-003837
• Status: Completed
• Phase: Phase 1
• Start date: May 24, 2022
• Est. completion date: August 25, 2023

Study information

• Verified date: September 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 25, 2023
• Est. primary completion date: August 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

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).

Locations

Country	Name	City	State
United States	Mayo Clinic Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 months

External Links

•   Mayo Clinic Clinical Trials