Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age

Dilated Cardiomyopathy Clinical Trial

Official title:

Effectiveness of Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age: A Hospital-Based Randomized Open Label Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06250257
• Other study ID #: JUIH/IRB/690/23
• Status: Recruiting
• Phase: Phase 3
• Start date: December 1, 2023
• Est. completion date: August 30, 2024

Study information

• Verified date: February 2024
• Source: Jimma University
• Contact: Kedir N Tukeni, MD
• Phone: +251913521475
• Email: Kedir.negesso[@]ju.edu.et
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Dilated cardiomyopathy (DCM) is a condition associated with Left and /or right ventricular (LV) dilatation and systolic dysfunction without coronary artery disease or abnormal loading circumstances proportionate to the severity of LV impairment. It is one of the leading causes of heart failure in younger adults, often requiring cardiac transplantation, and is caused by various factors, including myocarditis, alcohol, drug, and metabolic disturbances. About 35% of patients have genetic mutations affecting cytoskeletal, sarcomere, and nuclear envelope proteins. The prognosis depends on the severity and heart remodeling, with the worst outcomes in patients with low ejection fractions or severe diastolic dysfunction.

Although it is more common in men, DCM also occur in women, and hence hormonal factors can play a role in the development of DCM in women. Bromocriptine has been suggested as a potential treatment option. Bromocriptine is a dopamine agonist that is primarily used to treat conditions such as hyperprolactinemia, and acromegaly. However, it has also been studied in the context of heart failure, and some studies have suggested that it may be beneficial in women with Peripartal cardiomyopathy (PPCM), a form of DCM that occurs in the last month of pregnancy or up to five months postpartum.

The mechanism by which bromocriptine may improve left ventricular function in DCM is not fully understood, but it is thought to be related to its ability to reduce prolactin levels. Prolactin is a hormone that has been shown to be elevated in some cases of DCM, and it may contribute to the development and progression of the condition. To date, the use of bromocriptine is recommended for the treatment of pregnancy-related cardiomyopathy (PPCM) due to a significant increase in prolactin levels. However, prolactin level may increase during menstrual cycles of reproductive-age women, which candidates the use of bromocriptine in women of all reproductive ages. The aims of this study is to assess the use of bromocriptine in terms of LV function improvement, overall improvement of heart failure symptoms and reduced mortality and improved quality of life, in dilated cardiomyopathy among women of reproductive age.

Description:

Heart failure (HF) is a progressively deteriorating medical condition that significantly reduces both patients' life expectancy and quality of life. Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure in younger adults. Despite many progresses made in the past decades in the development of novel pharmacological treatments for HF, proper management of HF is still challenging and there remains a substantial unmet need in treating heart failure. Bromocriptine, an inhibiter of prolactin release by dopamine-D2-receptor, has been studied in the context of heart failure, and some studies have demonstrated its beneficial role in women with peripartum cardiomyopathy (PPCM). Prolactin level may also increase in of women reproductive-age, in which bromocriptine could also be a good candidate to use of in women of all reproductive ages. Although reports show beneficial role of bromocriptine in improving the left ventricular function in some patients with heart failure, the results may not be applicable to a wide range of populations and patients due to various sources of variation between populations. Thus, it would be relevant to conduct rigorous clinical trial to show the efficacy and safety of this treatment option in diverse populations like Ethiopians. It has been established that the same dose of a medication is associated with considerable heterogeneity in pharmacokinetics (PK) and pharmacodynamic (PD) efficacy and toxicity across human populations. This inter-individual difference in drug response can be explained by pharmacogenetic variations or other factors such as variations in patients' age and weight, co-morbidity, lifestyle, co-medication, renal and liver function, unfavorable drug-drug interactions and poor compliance of patients. The pharmacokinetics (PK) of bromocriptine in heart failure patients, the inter-individual variability in PK and clinical response and associated sources of variations have not been investigated before. Thus, this study is designed to investigate the effectiveness of bromocriptine in terms of efficacy and safety as well as the PK of bromocriptine among women of reproductive age with DCM in Ethiopia.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: August 30, 2024
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Age 18 years to 50 years

• ischemic or de novo dilated cardiomyopathy

Exclusion Criteria:

• Patients with severe comorbidities which may worsen their illness

• with hypertensive heart diseases

• Rheumatic valvular heart diseases

• Restrictive cardiomyopathy, constrictive cardiomyopathy, hypertrophic cardiomyopathy

• Congenital heart diseases

• Acute coronary syndrome

• Overt kidney failure (serum Creatinine = 1.4mg/dl),

• Women who are pregnant or lactating

• Previous adverse reaction to the bromocriptine

• Patients not willing to participate in the study

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy

Intervention

Drug:
• GDMT plus Bromocriptine mesylate
The treatment group will receive bromocriptine 2.5mg PO daily for 1 month together with GDMT.

Locations

Country	Name	City	State
Ethiopia	Jimma Medical Center	Jimma	Oromia

Sponsors (1)

Lead Sponsor	Collaborator
Jimma University

Country where clinical trial is conducted

Ethiopia, 

References & Publications (13)

Angaw DA, Ali R, Tadele A, Shumet S. The prevalence of cardiovascular disease in Ethiopia: a systematic review and meta-analysis of institutional and community-based studies. BMC Cardiovasc Disord. 2021 Jan 18;21(1):37. doi: 10.1186/s12872-020-01828-z. — View Citation

Halkein J, Tabruyn SP, Ricke-Hoch M, Haghikia A, Nguyen NQ, Scherr M, Castermans K, Malvaux L, Lambert V, Thiry M, Sliwa K, Noel A, Martial JA, Hilfiker-Kleiner D, Struman I. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopath — View Citation

Hilfiker-Kleiner D, Kaminski K, Podewski E, Bonda T, Schaefer A, Sliwa K, Forster O, Quint A, Landmesser U, Doerries C, Luchtefeld M, Poli V, Schneider MD, Balligand JL, Desjardins F, Ansari A, Struman I, Nguyen NQ, Zschemisch NH, Klein G, Heusch G, Schul — View Citation

Japp AG, Gulati A, Cook SA, Cowie MR, Prasad SK. The Diagnosis and Evaluation of Dilated Cardiomyopathy. J Am Coll Cardiol. 2016 Jun 28;67(25):2996-3010. doi: 10.1016/j.jacc.2016.03.590. — View Citation

Jefferies JL, Towbin JA. Dilated cardiomyopathy. Lancet. 2010 Feb 27;375(9716):752-62. doi: 10.1016/S0140-6736(09)62023-7. — View Citation

Misganaw A, Mariam DH, Ali A, Araya T. Epidemiology of major non-communicable diseases in Ethiopia: a systematic review. J Health Popul Nutr. 2014 Mar;32(1):1-13. — View Citation

Patten IS, Rana S, Shahul S, Rowe GC, Jang C, Liu L, Hacker MR, Rhee JS, Mitchell J, Mahmood F, Hess P, Farrell C, Koulisis N, Khankin EV, Burke SD, Tudorache I, Bauersachs J, del Monte F, Hilfiker-Kleiner D, Karumanchi SA, Arany Z. Cardiac angiogenic imb — View Citation

Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001 Nov 14;286(18):2270-9. doi: 10.1001/jama.286.18.2270. — View Citation

Reichart D, Magnussen C, Zeller T, Blankenberg S. Dilated cardiomyopathy: from epidemiologic to genetic phenotypes: A translational review of current literature. J Intern Med. 2019 Oct;286(4):362-372. doi: 10.1111/joim.12944. Epub 2019 Jul 29. — View Citation

Sliwa K, Blauwet L, Tibazarwa K, Libhaber E, Smedema JP, Becker A, McMurray J, Yamac H, Labidi S, Struman I, Hilfiker-Kleiner D. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study. Circul — View Citation

Sullivan KM, Dean A, Soe MM. OpenEpi: a web-based epidemiologic and statistical calculator for public health. Public Health Rep. 2009 May-Jun;124(3):471-4. doi: 10.1177/003335490912400320. No abstract available. — View Citation

Weintraub RG, Semsarian C, Macdonald P. Dilated cardiomyopathy. Lancet. 2017 Jul 22;390(10092):400-414. doi: 10.1016/S0140-6736(16)31713-5. Epub 2017 Feb 10. — View Citation

WHO CVD Risk Chart Working Group. World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions. Lancet Glob Health. 2019 Oct;7(10):e1332-e1345. doi: 10.1016/S2214-109X(19)30318-3. Epub 2019 Sep 2. Erra — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left ventricular function improvement	Left ventricular function change measured in terms of ejection fraction and fractional shortening.	at 3, 6 and 9 months
Primary	Improvement of cardiac biomarkers (N-terminal Pro BNP)	Change in cardiac biomarkers measured as N-terminal Pro BNP.	Measured at 3, 6 and 9 months
Secondary	Change in hospitalization pattern	Change in hospitalization as compared with measurements before and after intervention	At 9 months and 1 year
Secondary	Functional class of heart failure Improvement	Change in NYHAF class as measured clinically and compared to the baseline status.	At 9 months and one year
Secondary	Improved quality of life	Change in quality of life as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12) updated questionnaire, all KCCQ scores will be scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.	At 9 months and one year