Effect of Rapamycin to Improve Cardiac Function in Frail Older Adults

NCT ID: NCT04996719

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-24
• Study Completion Date: 2023-08-25

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.

Conditions

Heart Failure

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rapamycin

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

Group Type: EXPERIMENTAL

Rapamune

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

Rapamycin

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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mandeep Singh

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mandeep Singh, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic Rochester

Rochester, Minnesota, United States

Countries

United States

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

21-003837

Identifier Type: -

Identifier Source: org_study_id