Serotonin Receptor Blockers in Ischemic Mitral Regurgitation

NCT ID: NCT05469165

Last Updated: 2023-11-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-20
• Study Completion Date: 2027-09-30

Brief Summary

This study is intended to investigate the effect of cyproheptadine (a 5HT2B receptor blocker) on mitral regurgitation severity.

Detailed Description

Ischemic mitral regurgitation (MR) is a common and morbid complication of myocardial infarction (MI), doubling heart failure and mortality with currently limited therapies. Its mechanisms have been previously linked to left ventricle (LV) remodeling with secondary deformation of otherwise normal mitral leaflets. Recent studies are introducing new mechanistic elements, allowing possibilities for potential pharmacotherapeutic approaches. Normal mitral leaflets have the capacity to enlarge and adapt to even the largest LV dilatation to prevent MR. However, this compensatory mechanism is insufficient after MI, and the leaflets are abnormally thick with fibrotic changes. Those fibrotic changes could be related to a variation in blood serotonin (5-HT) levels after MI, which has been previously reported. Serotonin is a known cause of valve fibrosis through its 5HT type 2B receptor. In sheep models, the investigators have tested the hypothesis that a 5HT type 2B receptor blocker (cyproheptadine) can prevent adverse remodeling in the valve after MI. Cyproheptadine treatment was associated with increased valve leaflet surface, attenuated leaflet thickening and collagen deposition. Importantly, treated animals had less MR compared to non-treated animals.

Thus the present study is a double-blind randomized trial to assess the effect of cyproheptadine on MR severity, mitral valve surface variation, and left ventricular size following MI. Serial imaging (3D echo and MRI) will assess valve adaptation, LV remodeling and MR.

Conditions

Ischemic Mitral Regurgitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Cyproheptadine 4 Mg Oral Tablet

Participants will receive cyproheptadine 4mg tablet orally three times a day for three months, with a daily increase of 4mg/dose if the previous dose was well tolerated, up to 0.5 mg/kg/day.

Group Type: EXPERIMENTAL

Cyproheptadine 4 Mg Oral Tablet

Intervention Type: DRUG

Cyproheptadine treatment for 3 months

Placebo

Participants will receive a matched placebo orally three times a day for 3 months. Daily titration similar to the treatment arm.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo administration for 3months

Interventions

Cyproheptadine 4 Mg Oral Tablet

Cyproheptadine treatment for 3 months

Intervention Type: DRUG

Placebo

Placebo administration for 3months

Intervention Type: OTHER

Other Intervention Names

Cyproheptadine

Eligibility Criteria

Inclusion Criteria

1. Patients 18-80 years old with a 1st episode of STEMI with documented coronary obstruction.

2. Left ventricle ejection fraction (LVEF)<50% and mitral tenting area ≥ 4 cm2, OR LVEF ≤ 40% and inferior/posterior wall motion anomaly, OR LVEF≤30% and wall motion in any territory.

Exclusion Criteria

1. Inability to provide informed consent

2. Hemodynamic instability / cardiogenic shock / papillary muscle rupture

3. Prior mitral valve procedure/surgery

4. Permanent atrial fibrillation (limiting imaging and MR quantification)

5. Primary mitral disease (endocarditis, rheumatic, degenerative or congenital)

6. More than mild valvular disease (other than mitral) at baseline

7. Planned cardiac surgery (CABG or valve intervention) within 3 months

8. Contraindications for MRI

9. Ongoing treatment with selective serotonin reuptake inhibitor (SSRI)

10. Chronic use of sedative medication

11. Ongoing or planned pregnancy

12. Chronic renal failure with Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min

13. Neurocognitive disorder

14. Symptom or prior episode of urinary obstruction or glaucoma (relative contraindications for cyproheptadine)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Laval University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval

Québec, , Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Jonathan Beaudoin, MD

Role: CONTACT

jonathan.beaudoin@criucpq.ulaval.ca

(418) 656-8711 ext. 2943

Ons Marsit, PhD

Role: CONTACT

ons.marsit.1@ulaval.ca

(418) 656-8711 ext. 5773

Facility Contacts

Jonathan Beaudoin, MD

Role: primary

418 656-8711 ext. 2943

Other Identifiers

22229

Identifier Type: -

Identifier Source: org_study_id