Modulation of SERCA2a of Intra-myocytic Calcium Trafficking in Heart Failure With Preserved Ejection Fraction
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: AAV1/SERCA2a.
- Who it may be relevant to
- Registry conditions: Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction. Basic parameters: from 50 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase 1b, Pilot Trial Evaluating the Safety and Pharmacodynamic Effects of SRD-001 (AAV1-SERCA2a) in Subjects With Heart Failure With Preserved Ejection Fraction
Overview
The goal of this clinical trial is to test an experimental gene therapy in participants with heart failure with preserved ejection fraction, also known as diastolic heart failure. The main questions it aims to answer are: * safety and tolerability of the gene therapy; and * whether the gene therapy helps the heart ventricles relax during filling. Participants will undergo a one-time infusion of the gene therapy in the cardiac catheterization laboratory and then be followed for safety and effects on left-sided filling pressures while exercising. The first year will have multiple in-person visits followed by 4 years of biannual phone calls.
Detailed description
Eligible participants will undergo a one-time antegrade epicardial coronary artery infusion of gene therapy delivered to the 3 major cardiac territories of the left ventricle of the heart (anterior, lateral, inferior/posterior) or bypass grafts unless contraindicated. Post-procedure, the subject will be monitored continuously for a minimum of 4 hours and then discharged to home that same day if medically appropriate. Participants will be followed for 52 weeks as part of the main trial. On Day 2 and Week 1, subjects will be contacted by phone for a general safety assessment, and if clinically indicated, an in-person evaluation and assessment will be performed as soon as possible. On Weeks 2, 4, 12, 24 and 52, subjects will undergo general safety assessments. Additionally, at Weeks 24 and 52, subjects will undergo outpatient core resting and exercise transthoracic echocardiography, right heart catheterization with hemodynamic monitoring and gas exchange measurements, 6-minute wall test, cardiac biomarker testing and completion the Kansas City Cardiomyopathy Questionnaire. Upon completion of the active observation period, participants will continue to be followed for 4 years with bi-annual, semi-structured telephone or in-person questionnaires that collect information on overall status and other comorbid conditions of interest in gene therapy trials.
Interventions
- Biological AAV1/SERCA2a
3E13 viral genomes fixed dose
Primary outcome measures
- Change in pulmonary capillary wedge pressure (PCWP) [Time frame: Week 24 and Week 52]
Secondary outcome measures (11)
- Change in PCWP at 20W exercise [Time frame: Week 24 and Week 52]
- Change in oxygen uptake (VO2) during exercise [Time frame: Week 24 and Week 52]
- Change in left ventricular (LV) relaxation [Time frame: Week 24 and Week 52]
- Change in NT-proBNP [Time frame: Week 24 and Week 52]
- Change in left atrial end systolic volume [Time frame: Week 24 and Week 52]
- Change in left atrial reservoir strain [Time frame: Week 24 and Week 52]
- Change in left atrial contractile strain [Time frame: Week 24 and Week 52]
- Change in 6 Minute Walk Distance [Time frame: Week 24 and Week 52]
- Change in 6 Minute Walk Test Borg scale [Time frame: Week 24 and Week 52]
- Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score [Time frame: Week 24 and Week 52]
- Change in New York Heart Association class [Time frame: Week 24 and Week 52]
Eligibility criteria
Inclusion criteria
- Willing and able to provide informed consent
- Negative for anti-AAV1 neutralizing antibodies
- NYHA class II or III
- Left ventricular ejection fraction ≥ 50%
- Evidence of resting or exercise-induced left ventricle filling pressure
- On oral diuretic therapy
- Adequate birth control
Exclusion criteria
- NYHA class IV
- Heart failure requiring hospitalization in the past 3 months
- Manifested or provocable ischemic heart disease
- Atrial fibrillation
- History of congenital heart disease, restrictive or infiltrative cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis, pericardial disease, uncorrected thyroid disease or discrete left ventricular (LV) aneurysm
- History of amyloidosis
- Untreated left-sided valvular disease
- Severe COPD
- BMI > 50 kg/m\^2
- Severe liver, kidney or hematologic dysfunction
- Cancer within the past 5 years
- Unstable concurrent conditions
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 2 centers
- Duke University — Durham
- University of Texas Southwestern Medical Center — Dallas
Publications
- Fudim M, Sarma S, MacNamara JP, Ascheim DD, Kittipibul V, Doukellis K, Dhimitri A, Fitzhugh R, Kamat N, Costa KD, Rudy J, Guerrero J, Chan C, Li RA, Bavry AA, Patel MR, Grodin JL, Levine BD, Hajjar RJ. Rationale and design of MUSIC-HFpEF: a phase 1b, pilot trial evaluating the safety and pharmacodynamic effects of AAV1.SERCA2A in heart failure with preserved ejection fraction. Heart Fail Rev. 2026 PMID 41546750
Identifiers
NCT: NCT06061549 · SRD-001-1003