Cyproheptadine for Mitral Valve Regurgitation
(CYPRO-MR Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Laval University
Must not be taking: SSRIs, Sedatives
Disqualifiers: Atrial fibrillation, Pregnancy, Renal failure, others
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This study is intended to investigate the effect of cyproheptadine (a 5HT2B receptor blocker) on mitral regurgitation severity.
Will I have to stop taking my current medications?
The trial requires that you stop taking selective serotonin reuptake inhibitors (SSRIs) and sedative medications. If you are on these medications, you would need to discontinue them to participate.
Is cyproheptadine generally safe for humans?
How does the drug cyproheptadine differ from other treatments for mitral valve regurgitation?
Cyproheptadine is unique because it has inhibitory activities for calcium channels and serotonin receptors, which might offer a novel approach to treating mitral valve regurgitation, a condition with limited standard drug treatments. Its potential to affect calcium channels could influence heart function differently than traditional therapies.46789
Eligibility Criteria
This trial is for adults aged 18-80 who've had a first heart attack with blocked arteries and have specific types of heart muscle damage or weakness. It's not for those on sedatives, pregnant, with severe kidney issues, unable to consent, permanent irregular heartbeat, other major valve diseases, planned heart surgery soon, MRI contraindications, on antidepressants (SSRIs), cognitive disorders or at risk for urinary blockage/glaucoma.Inclusion Criteria
My heart's pumping ability is reduced and I have specific heart valve or wall motion issues.
I am between 18 and 80 years old and have had my first heart attack with a blocked artery.
Exclusion Criteria
I am scheduled for heart surgery within the next 3 months.
My heart valve condition is due to infection, rheumatic disease, wear and tear, or was present at birth.
My kidney function is severely reduced.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive cyproheptadine or placebo orally three times a day for 3 months, with dose titration based on tolerance
3 months
Regular visits for dose titration and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, including imaging and health status assessments
9 months
Periodic visits for imaging and assessments
Treatment Details
Interventions
- Cyproheptadine 4 Mg Oral Tablet (5HT2B receptor blocker)
- Placebo (Other)
Trial OverviewThe study tests if cyproheptadine (a serotonin receptor blocker) can reduce the severity of leaky mitral valves in the heart after an ischemic event like a heart attack. Participants will either receive cyproheptadine tablets or placebo pills without active medication.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Cyproheptadine 4 Mg Oral TabletExperimental Treatment1 Intervention
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 II: PlaceboPlacebo Group1 Intervention
Participants will receive a matched placebo orally three times a day for 3 months. Daily titration similar to the treatment arm.
Cyproheptadine 4 Mg Oral Tablet is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Periactin for:
- Allergic Reactions
- Allergic Rhinitis
- Allergies
- Anorexia
- Anorexia Nervosa
- Cluster Headaches
- Cushing's Syndrome
- Failure to Thrive
- Migraine
- Pruritus
- Sexual Dysfunction, SSRI Induced
- Unintentional Weight Loss (Underweight)
- Urticaria
🇪🇺 Approved in European Union as Periactin for:
- Allergic Reactions
- Migraine Prevention
- Hay Fever
- Cyclical Vomiting Syndrome
- Psychogenic Itch
- Drug-induced Hyperhidrosis
- Prevention of Blister Formation in Epidermolysis Bullosa Simplex
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Institut universitaire de cardiologie et de pneumologie de Québec - Université LavalQuébec, Canada
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Who Is Running the Clinical Trial?
Laval UniversityLead Sponsor
Canadian Institutes of Health Research (CIHR)Collaborator
References
Teratogenicity of cyproheptadine in pregnant rats. [2013]The teratogenicity of cyproheptadine HCL (Periactin) was studied in 3 groups of pregnant rats which received respectively 0.5 mg/kg/day, 2.5 mg/kg/day and 5 mg/kg/day cyproheptadine subcutaneously and in a control group of pregnant rats which received 0.2 ml/day of the solvent normal saline. Higher doses were toxic to pregnant rats. There was no significant difference in the birth rate, foetal resorption rate and malformation rate between the 4 groups. Moreover, there was no significant difference between average weights, average foetal placental weights and male/female ratio in the experimental and control foetuses. It is concluded that cyproheptadine is devoid of any teratogenic effect in rats.
Safety of Cyproheptadine, an Orexigenic Drug. Analysis of the French National Pharmacovigilance Data-Base and Systematic Review. [2021]Objectives: Cyproheptadine is a first-generation H1-antihistamine drug first that was distributed in the 1960s. While its orexigenic effect was observed early, cyproheptadine is not yet authorized for this indication in all countries today. There is an increasing medical interest and demand for the orexigenic effect of cyproheptadine, especially in children with poor appetite. As cyproheptadine might be evaluated in future clinical trials, we wanted to assess its safety profile. Methods: Using the French national pharmacovigilance database, we retrospectively analyzed all pediatric and adult reports of adverse effects of cyproheptadine recorded since its first distribution in France. Next, we performed a systematic review of the literature of cyproheptadine adverse effects. Results: Since 1985, 93 adverse effects were reported in the French pharmacovigilance database (adults 81.7%, children 18.3%); these were mainly neurological symptoms (n = 38, adults 71%, children 28.9%), and hepatic complications (n = 15, adults 86.7%, children 13.3%). In the literature, the most frequent adverse effect reported was drowsiness in adults or children, and five case reports noted liver complications in adults. We estimated the frequency of hepatic adverse effects at 0.27 to 1.4/1000, regardless of age. Conclusion: Cyproheptadine can be considered a safe drug. Mild neurological effects appear to be frequent, and hepatotoxicity is uncommon to rare. Randomized controlled trials are needed to evaluate the safety and efficacy of cyproheptadine before authorization for appetite stimulation, especially in young children as studies at this age are lacking. Possible hepatic complications should be monitored, as very rare cases of liver failure have been reported.
A fatality due to cyproheptadine and citalopram. [2022]Cyproheptadine (Periactin) is a first-generation antihistamine available in over-the-counter cold medications and is used to treat allergic-type symptoms. Although antihistamines in general have long been known to cause serious side effects, especially when taken in overdose, few reports that specifically address cyproheptadine-related fatalities exist. A 42-year-old healthy female was found dead at her home with no anatomic cause of death and a recent history of suicidal ideations. Toxicology revealed cyproheptadine and citalopram in the femoral postmortem blood at concentrations of 0.49 and 2.3 mg/L, respectively. Vitreous, urine, and bile analysis were also performed, yielding concentrations of
Discovery, structure-activity relationship study, and oral analgesic efficacy of cyproheptadine derivatives possessing N-type calcium channel inhibitory activity. [2014]Antiallergic drug cyproheptadine (Cyp) is known to have inhibitory activities for L-type calcium channels in addition to histamine and serotonin receptors. Since we found that Cyp had an inhibitory activity against N-type calcium channel, Cyp was optimized to obtain more selective N-type calcium channel blocker with analgesic action. As a consequence of the optimization, we found 13 with potent N-type calcium channel inhibitory activity which had lower inhibitory activities against L-type calcium channel, histamine (H1), and serotonin (5-HT2A) receptors than those of Cyp. 13 showed an oral analgesic activity in rat formalin-induced pain model.
Comparison of a new antihistamine HC 20-511 with cyproheptadine (Periactin) in chronic urticaria. [2019]The effect and tolerance of a new antihistamine, HC 20-511, in daily doses of 2 and 4 mg was compared with cyproheptadine (Periactin) 8 mg daily in 50 cases of chronic urticaria. HC 20-511 4 mg daily proved to be the most effective, rapid and long-lasting. HC 20-511 had less sedative effect than cyproheptadine, but both possessed the same appetite-stimulating effect. However, this was not noted with the smaller dosage of HC 20-511.
Cyproheptadine analogues: synthesis, antiserotoninergic activity, and structure-activity relationships. [2019]A series of cyproheptadine related compounds was synthesized and tested pharmacologically. In comparison with cyproheptadine, these compounds do not have a central ring and some contain groups other than N-methyl. Synthesis was carried out with low-valent titanium to generate the exocyclic double bond. The serotoninergic activity of the compounds was determined by standard determination of pA2 (-log of the motor concentration of antagonist required to maintain a constant response when concentration of agonist is doubled) for the inhibition of serotonin-induced contractions in rat stomach fundus. Two of the nitrogen-containing compounds were active, but their activities were lower than that of cyproheptadine. Structure-activity relationships were studied by Mulliken net charges, molecular electrostatic potentials, and conformational analysis; activities are better correlated with electrostatic potentials than with net charges. The decrease in potency of the open cyproheptadine analogues may be due to "dilution" of the active conformer as the result of their conformational flexibility.
Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review. [2020]A systematic review identifying the use of cyproheptadine (CY) as an appetite stimulant was completed.
(+)- and (-)-3-Methoxycyproheptadine. A comparative evaluation of the antiserotonin, antihistaminic, anticholinergic, and orexigenic properties with cyproheptadine. [2019]The synthesis and resolution of (+/-)-3-methoxycyproheptadine [(+/-)-4] are described. As a peripheral serotonin antagonist, (+/-)-4 was found to be one-half as potent as cyproheptadine (1b). The peripheral anticholinergic and antihistaminic activities as well as the orexigenic property of (+/-)-4 are less than those of 1b. A further comparison of the enantiomers (+)-4 and (-)-4 shows that all of the anticholinergic activity of (+/-)-4 resides solely in the dextrorotatory enantiomer, (+)-4, while the antiserotonin activity, which is similar to that of 1b, resides in the levorotatory enantiomer, (-)-4. Antihistaminic and orexigenic activity also resides in (-)-4 but these properties are reduced compared to those of 1b.
Failure of cyproheptadine hydrochloride as an antipruritic agent in allergic dogs: results of a double-blinded, placebo-controlled study. [2013]Cyproheptadine hydrochloride was administered orally at 0.1 to 0.2 mg/kg/day to 16 dogs with allergic pruritus. No dog improved. Polyphagia was observed in 4 dogs (25%).