Clomiphene Citrate Plus Cabergoline in Treatment of Polycystic Ovary Syndrome

Clomiphene Citrate Plus Cabergoline Versus Clomiphene Citrate Alone in Treatment of Polycystic Ovary Syndrome Associated Infertility

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive aged women and affects approximately 5-12 % of the female population.

In 2003 in Rotterdam , Rotterdam diagnostic criteria were redefined PCOS as affected individuals must have two out of the following three criteria:

1. Oligo- and/or anovulation, (ovulation occurs less than once every 35 days).
2. Hyperandrogenism, clinical signs include hirsutism, acne, alopecia, and frank virilization, while chemical indicators include raised concentrations of total testosterone and androstenedione , and elevated free androgen index.
3. Polycystic ovaries on sonographic examination, presence of 12 or more follicles in either ovary measuring 2-9 mm in diameter, increased ovarian volume more than 10 cm3 and/or increase in stromal echogenicity. Clearly, according to the Rotterdam diagnostic criteria, the majority of women with PCOS can be diagnosed without the need of laboratory examinations.

Clomiphene citrate (CC) is still the first-line medication for the induction of ovulation. It is an anti-estrogenic compound made up of two isomers, enclomiphene and zuclomiphene; the latter being the more potent of the two. It is a non-steroidal compound closely resembling estrogen. CC acts by blocking estrogen receptors, particularly in the hypothalamus, thereby signaling a lack of circulating estrogens and inducing a change in the pulsatile release of gonadotrophin-releasing hormone (GnRH). This induces release of follicle stimulating hormone from the anterior pituitary and is often enough to set the cycle of events leading to ovulation into motion.

Cabergoline, ergot-derived dopamine agonists with a very long half life, is an effective prolactin suppressor. Cabergoline oral administration contains a weekly dose of 0.5 - 3 mg, which could be increased, if needed, to twice a week. This medicine has slight dopamine agonistic side effects, headache being the most common one. Treatment in the very beginning should start with a partial dose (half a pill) at bedtime with a small amount of food. Low incidence of side effects and its weekly dose has made Cabergoline a choice drug for treatment of related diseases.

Study Overview

• Status: Unknown
• Conditions: Female Reproductive Problem
• Intervention / Treatment: Drug: Clomiphene citrate; Drug: Cabergoline; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kamal M Zahran, MD; Phone Number: +20882414616; Email: drzahranmk@gmail.com
• Study Contact Backup: Name: Mohammed K Ali, MD; Phone Number: +20882414621; Email: m_khairy2001@yahoo.com

Study Locations

• Egypt
  • Assiut, Egypt, 71111
    • Recruiting
    • Assiut University
    • Contact: Kamal M Zahran, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 2 or more of PCOS signs according to Rotterdam diagnostic criteria (2003).-
• Primary or secondary infertility.-
• Absence of galactorrhoea
• Normal serum prolactin or slightly elevated (up to 50 ng/dl)
• Normal hysterosalpingography
• Normal spermogram

Exclusion Criteria:

• Women on other line of treatment as aromatase inhibitors, gonadotrophins, or tamoxifen.
• Known hypersensitivity for Clomiphene citrate or cabergoline.
• Other factors of infertility as tubal factor, uterine factor or male factor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clomiphene citrate plus cabergoline; This group will receive Clomiphene citrate 50 mg tablet twice daily from the second day of menses to the sixth day plus cabergoline 0.25 mg from second day every 3 days (4 doses only)	Drug: Clomiphene citrate; 50 mg tablet twice daily from the second day of menses to the sixth day; Drug: Cabergoline; Cabergoline 0.25 mg (half tablet) every 3 days (4 doses).
Active Comparator: Clomiphene citrate plus placebo; This group will receive Clomiphene citrate 50 mg tablet twice daily from the second day of menses to the sixth day plus placebo tablets from second day every 3 days (4 doses only)	Drug: Clomiphene citrate; 50 mg tablet twice daily from the second day of menses to the sixth day; Other: Placebo; placebo(half tablet) every 3 days (4 doses).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Size of mature follicles (mm).	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of pregnancy	1 year
Number of mature follicles (mm)	1 year

Collaborators and Investigators

• Sponsor: Woman's Health University Hospital, Egypt

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: October 13, 2015
• First Submitted That Met QC Criteria: December 28, 2015
• First Posted (Estimate): December 31, 2015

Study Record Updates

• Last Update Posted (Estimate): June 29, 2016
• Last Update Submitted That Met QC Criteria: June 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Dopamine Agonists; Dopamine Agents; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Antiparkinson Agents; Anti-Dyskinesia Agents; Clomiphene; Enclomiphene; Zuclomiphene; Cabergoline
• Other Study ID Numbers: CC in PCOS