Ischemic Mitral RegurgitationPhase 2CYPRO-MRNCT05469165
Serotonin Receptor Blockers in Ischemic Mitral Regurgitation
A Phase 2 study testing Cyproheptadine 4 Mg Oral Tablet in people with Ischemic Mitral Regurgitation, run by Laval University at 1 site in Canada.
Trial summary
This study is intended to investigate the effect of cyproheptadine (a 5HT2B receptor blocker) on mitral regurgitation severity. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ischemic Mitral Regurgitation
- What is being tested?
- Cyproheptadine 4 Mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 214 participants
- Where
- 1 siteCanada
- Study dates
- 20 Jun 2023to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18-80 years old with a 1st episode of STEMI with documented coronary obstruction.
- 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.
Who cannot join
- Inability to provide informed consent
- Hemodynamic instability / cardiogenic shock / papillary muscle rupture
- Prior mitral valve procedure/surgery
- Permanent atrial fibrillation (limiting imaging and MR quantification)
- Primary mitral disease (endocarditis, rheumatic, degenerative or congenital)
- More than mild valvular disease (other than mitral) at baseline
Show all 14Show fewer
- Planned cardiac surgery (CABG or valve intervention) within 3 months
- Contraindications for MRI
- Ongoing treatment with selective serotonin reuptake inhibitor (SSRI)
- Chronic use of sedative medication
- Ongoing or planned pregnancy
- Chronic renal failure with Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min
- Neurocognitive disorder
- Symptom or prior episode of urinary obstruction or glaucoma (relative contraindications for cyproheptadine)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
Québec, G1V 4G5
Jonathan Beaudoin, MD, 418 656-8711 ext. 2943
About this study
Official title: Blocking the Effects of Serotonin to Prevent Ischemic Mitral Regurgitation: a Randomized Trial (CYPRO-MR)
This study is intended to investigate the effect of cyproheptadine (a 5HT2B receptor blocker) on mitral regurgitation severity.
Read the 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
- Being tested
- Cyproheptadine 4 Mg Oral Tablet, Placebo
- Keywords
- Ischemic mitral regurgitation, Myocardial infarction, Mitral valve, Serotonin, Cyproheptadine
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyproheptadine 4 Mg Oral TabletDrug
Also called Cyproheptadine
Cyproheptadine treatment for 3 months
PlaceboOther
Placebo administration for 3months
| Study group | Role | What they receive |
|---|---|---|
| Cyproheptadine 4 Mg Oral Tablet | Experimental | 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. Receives: Drug: Cyproheptadine 4 Mg Oral Tablet |
| Placebo | Placebo comparator | Participants will receive a matched placebo orally three times a day for 3 months. Daily titration similar to the treatment arm. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mitral regurgitation severity
Incidence of more than mild MR (MRI regurgitant fraction ≥ 20%) at 3 months (measured by MRI)
Measured: Baseline, 3 months
Secondary outcomes (14)
Change in mitral leaflet size
Mitral leaflet size (3D echo) and its variation vs baseline (measured by echocardiography)
Measured: Baseline, 3 months
Change in mitral regurgitation grade
Mitral regurgitation grade (measured by echocardiography). Mitral regurgitation is graded on a scale of I-IV (grade I (mild MR), grade II (moderate MR), grade III (moderate-to-severe MR) and grade IV (severe MR)). A higher mitral regurgitation grade is generally associated with a worse outcome for the patient.
Measured: Baseline, 3 months
Change in left ventricle size
Left ventricle size (measured by MRI )
Measured: Baseline, 3 months
Change in left ventricle function
Left ventricle function (measured by MRI )
Measured: Baseline, 3 months
Incidence of other valve regurgitation
Incidence of other valve regurgitation (more than mild) (measured by echocardiography)
Measured: 3 months
Change in mitral valve thickness
Mitral valve thickness (measured by echocardiography)
Measured: Baseline, 3 months
Adverse events
Composite of: Mortality, Heart failure requiring hospital admission, Mitral valve intervention (surgical/percutaneous)
Measured: 3 months and 1 year
Ischemic events
stroke and myocardial infarction
Measured: 3 months and 1 year
Bleeding events
Bleeding Academic Research Consortium (BARC) definition
Measured: 3 months and 1 year
Change in weight of participants
Weight gain during therapy (self-assessment by participants)
Measured: Baseline, 3 months
Change in the patient's perception of their health status
Self-administered questionnaire : Kansas City Cardiomyopathy Questionnaire (KCCQ). All score are represented on a 0-to-100-point scale (lower scores represent more severe symptoms and/or limitations and scores of 100 indicate no symptoms, no limitations, and excellent quality of life).
Measured: Baseline, 3 months
Change in the functional capacity of participants
6-minutes walk test
Measured: 3 months, 1 year
Incidence of sedation
Incidence of sedation (reported by participants)
Measured: Baseline, 3 months
Change in depression score
Self-administered questionnaire: Patient Health Questionnaire (PHQ-9). The Patient Health Questionnaire has a scale of 0-27, with higher scores indicating a worse outcome for the patient, with more severe depression symptoms.
Measured: Baseline, 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2022
- Study start20 Jun 2023
- Primary completionSep 2026 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic Mitral RegurgitationStudies of the same condition, open and under way.
- More trials run by Laval UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 214 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Laval University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05469165
- Sponsor's protocol ID
- 22229
- Acronym
- CYPRO-MR
- Status last verified
- Nov 2023
- First submitted
- 19 Jul 2022
- Last updated
- 15 Nov 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blocking the Effects of Serotonin to Prevent Ischemic Mitral Regurgitation: a Randomized Trial (CYPRO-MR)
- ClinicalTrials.gov ID
- NCT05469165
- Acronym / sponsor ID
- CYPRO-MR / 22229
- Conditions
- Ischemic Mitral Regurgitation
- Keywords
- Ischemic mitral regurgitation, Myocardial infarction, Mitral valve, Serotonin, Cyproheptadine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 214 participants (estimated)
- Lead sponsor
- Laval UniversityUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 20 Jun 2023 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 21 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyproheptadine 4 Mg Oral Tablet | Experimental | Drug: Cyproheptadine 4 Mg Oral TabletParticipants 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. |
| Placebo | Placebo comparator | Other: PlaceboParticipants will receive a matched placebo orally three times a day for 3 months. Daily titration similar to the treatment arm. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients 18-80 years old with a 1st episode of STEMI with documented coronary obstruction.
- 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.
Key exclusion criteria (14 listed)
- Inability to provide informed consent
- Hemodynamic instability / cardiogenic shock / papillary muscle rupture
- Prior mitral valve procedure/surgery
- Permanent atrial fibrillation (limiting imaging and MR quantification)
- Primary mitral disease (endocarditis, rheumatic, degenerative or congenital)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyproheptadine 4 Mg Oral TabletAlso: CyproheptadineCyproheptadine treatment for 3 months | Drug | Cyproheptadine 4 Mg Oral Tablet |
| PlaceboPlacebo administration for 3months | Other | Placebo |
Primary outcome
Change in mitral regurgitation severity
Time frame: Baseline, 3 months
Incidence of more than mild MR (MRI regurgitant fraction ≥ 20%) at 3 months (measured by MRI)
14 secondary outcomes
Change in mitral leaflet size
Time frame: Baseline, 3 months
Change in mitral regurgitation grade
Time frame: Baseline, 3 months
Change in left ventricle size
Time frame: Baseline, 3 months
Change in left ventricle function
Time frame: Baseline, 3 months
Incidence of other valve regurgitation
Time frame: 3 months
Change in mitral valve thickness
Time frame: Baseline, 3 months
Adverse events
Time frame: 3 months and 1 year
Ischemic events
Time frame: 3 months and 1 year
Bleeding events
Time frame: 3 months and 1 year
Change in weight of participants
Time frame: Baseline, 3 months
Change in the patient's perception of their health status
Time frame: Baseline, 3 months
Change in the functional capacity of participants
Time frame: 3 months, 1 year
Incidence of sedation
Time frame: Baseline, 3 months
Change in depression score
Time frame: Baseline, 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyproheptadine 4 Mg Oral Tablet in people with Ischemic Mitral Regurgitation, run by Laval University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jonathan Beaudoin, MD ((418) 656-8711 ext. 2943, jonathan.beaudoin@criucpq.ulaval.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mitral regurgitation severity (time frame: Baseline, 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2023.