Effect of Bromocriptine on Insulin Resistance in Polycystic Ovarian Syndrome - A Pilot Study (PCOS-Pilot)

• ClinicalTrials.gov Identifier: NCT02133755
• Recruitment Status: Unknown
• First Posted: May 8, 2014
• Last Update Posted: May 8, 2014
• Sponsor: IWK Health Centre
• Information provided by (Responsible Party): Cora fanning, IWK Health Centre

Study Description

Brief Summary:

The primary aim of this study is to determine the effect of dopamine agonist therapy on insulin resistance in lean vs. obese women with polycystic ovary syndrome. Polycystic ovary syndrome (PCOS) is a common metabolic abnormality in women. The diagnosis of PCOS relies on a constellation of symptoms and signs (problems with ovulation, clinical and/or biochemical signs of hyperandrogenism and cystic ovaries). Though not a diagnostic feature, insulin resistance (IR) is a hallmark of PCOS and up to 80% women with PCOS have IR. Although IR is more significant in obese women with PCOS, even lean women can be insulin resistant. No current therapy addresses the problem of insulin resistance in PCOS. Studies have suggested a dopamine deficiency in patients with PCOS, which may underlie the insulin resistance and may have a pathogenetic role in the development of PCOS. No study to date has assessed the impact of dopamine agonist therapy on IR in patients with PCOS.

Condition or disease	Intervention/treatment	Phase
PCOS; Insulin Resistance	Drug: Bromocriptine	Phase 3

Detailed Description:

Does bromocriptine improve measures of insulin resistance in females with polycystic ovarian syndrome and is there a differential benefit based on Body Mass Index (BMI, kg/m2).

This study will use a single subject design where patients with PCOS will have regular clinical laboratory tests before and after treatment with bromocriptine. It is a pilot study comprised of 20 women with normal BMI (<25) and 40 women with BMI ≥27.

Study data will be collected from participants during regularly scheduled clinic visits (enrolment) and 3 months later (follow-up). Standard care examinations, blood work and pelvic ultrasound will be performed and included as the study data.

The main outcome of interest will be to evaluate the change in HOMA-IR (Homeostatic Model Assessment - Insulin Resistance) from baseline. It is calculated using a fasting glucose and insulin level. Additionally, to determine the magnitude of effect on HOMA-IR as a measure of insulin sensitivity in lean compared to obese women and the effect on insulin sensitivity in those with and without insulin resistance.

Other measure of interest will be a change in glycated hemoglobin (A1C), serum androgens and pituitary hormone levels. No additional tests will be obtained above what is done in the course of usual assessment of patients with PCOS

Change in HOMA-IR values will be calculated for each individual patient and tested using a paired t-test to determine if therapy had a significant impact on HOMA-IR values. A multivariate linear regression will then be applied to determine if this change in HOMA-IR values was influenced by either BMI or baseline HOMA-IR value along with any other potentially confounding variables.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: Effect of Bromocriptine on Insulin Resistance in Polycystic Ovarian Syndrome - A Pilot Study
• Study Start Date: July 2014
• Estimated Primary Completion Date: July 2015
• Estimated Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Bromocriptine mesylate (Cycloset); Cycloset 1.6 to 3.2 mg daily for 3 months	Drug: Bromocriptine; Three month administration of bromocriptine. Baseline ultrasound and laboratory parameters measured. Repeat measures at discontinuation of drug at 3 months.; Other Name: Cycloset

Outcome Measures

Primary Outcome Measures :

1. Insulin Resistance (IR) [ Time Frame: 3 months ]
   Will bromocriptine improve measures of IR in females with PCOS? IR is a reduced glucose response for given concentration of insulin. IR can be estimated from fasting glucose and insulin levels using the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) equation: HOMA-IR = fasting plasma glucose (mmol/L) x fasting serum insulin (μU/mL) / 22.5. HOMA-IR correlates well with estimates using the euglycemic clamp method (r = 0.88). A recent study of healthy, young, insulin sensitive, Canadian subjects found that HOMA IR values were 0.78 for Caucasians, 0.82 for East Asians and 1.08 for South Asians. While this demonstrates some ethnic variability, the values for insulin sensitive individuals are lower than traditional cut-off values. With this in mind, and an understanding of the inherent limitations of HOMA-IR, we have chosen a cut-off value of 2, above which we will define insulin resistance and below which, patients will be considered to be insulin sensitive.

Secondary Outcome Measures :

1. IR based on BMI [ Time Frame: 3 months ]
   Is there a differential benefit in insulin resistance reduction based on Body Mass Index (BMI, kg/m2)?

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• women age 18 to 45 years with PCOS willing to maintain consistent weight for 3 month study period

Exclusion Criteria:

• diabetes other conditions associated with insulin resistance previous intolerance to dopamine agonist therapy concomitant medication that would interfere with dopamine agonist therapy insulin resistance syndrome type A or Type B

Contacts and Locations

Locations

Canada, Nova Scotia

IWK Health Centre

Halifax, Nova Scotia, Canada, B3K 6R8

Contact: Renda Bouzayen, MD, FRCSC 902-470-6457 renda.bouzayen@iwk.nshealth.ca

Contact: Cora Fanning, BN 902-470-7158 cora.fanning@iwk.nshealth.ca

Principal Investigator: Renda Bouzayen, MD, FRCSC

Sponsors and Collaborators

IWK Health Centre

Investigators

• Principal Investigator: Ali Imran, MD, FRCPC; QE II Health Science Centre

More Information

• Responsible Party: Cora fanning, Research Coordinator, IWK Health Centre
• ClinicalTrials.gov Identifier: NCT02133755
• Other Study ID Numbers: PCOS-Pilot
• First Posted: May 8, 2014
• Last Update Posted: May 8, 2014
• Last Verified: May 2014

Additional relevant MeSH terms:

Polycystic Ovary Syndrome; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine System Diseases; Bromocriptine; Antiparkinson Agents; Anti-Dyskinesia Agents; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Dopamine Agonists; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action