Effects of Cyproterone Compound-spironolactone, Metformin and Pioglitazone on Inflammatory Markers in PCOS (AntiPCO)

Effects of Treatment With Cyproterone Compound-spironolactone, Metformin and Pioglitazone on Serum Inflammatory Markers in Patients With Polycystic Ovary Syndrome (PCOS)

The aim of this study is to evaluate the effects of three-month course of treatment modalities (Cyproterone compound-Spironolactone, Metformin and Pioglitazone) in patients with polycystic ovary syndrome (PCOS) on markers of inflammation [serum complement, homocysteine and high sensitive C-reactive protein (hs-CRP)] levels.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Cyproterone compound + Spironolactone; Drug: Metformin; Drug: Pioglitazone

Detailed Description

Polycystic ovary syndrome (PCOS) is estimated to affect up to10% of women of reproductive age, making it one of the most common endocrine disorders in this population. PCOS is associated with a broad range of adverse sequel, including hypertension, dyslipidemia, insulin resistance, hyperandrogenaemia, gestational and type 2 diabetes,which ultimately increase the cardiovascular morbidity in these patients. Also PCOS is increasingly recognized as a component of the metabolic syndrome. Management depends on symptoms or the source of androgen excess. Several treatment options are available, which allows for an individualized approach. Spironolactone is the safest potent available antiandrogen. It is effective in lowering the hirsutism score by approximately one third, although considerable individual variations exist. Other antiandrogens used to treat hirsutism and hirsutism equivalents include cyproterone acetate that has weak antiglucocorticoid effects. Metformin and thiazolidinediones, are promising adjuncts for treating PCOS. Although both of them increase insulin sensitivity, but their mechanism of action differ.

Serum complement, homocysteine and C-reactive protein (CRP) levels have been reported to be linked with insulin resistance.

The investigators want to measure serum complement, homocysteine and hs-CRP levels in patients with PCOS before and after three-month course of treatment with Cyproterone compound-Spironolactone (CC-S), metformin (M) and pioglitazone (P).

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Fars
    • Shiraz, Fars, Iran, Islamic Republic of
      • Shahid Motahhari Clinic, Shiraz University of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 31 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age 18-35 years

• Diagnosis of Polycystic Ovary Syndrome (PCOS) according to Rotterdam criteria 2003 (two out of three required):

  1. Oligomenorrhea or anovulation
  2. Clinical and/or biochemical signs of hyperandrogenism
  3. Polycystic ovaries (by ultrasound)

Exclusion Criteria:

• Smoking
• Pregnancy
• Diabetes mellitus
• Renal failure (serum creatinine >1.5)
• Congenital adrenal hyperplasia
• Hyper or hypothyroidism
• Sex hormone therapy or antiandrogen therapy during the last three months
• Unexplained serum alanin aminotransferase (ALT) elevation more than 2.5 times above normal range
• Any systemic or febrile illnesses
• Use of glucocorticoid or anti-inflammatory drugs during the last three months
• Androgen secreting tumor
• Malignancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cyproterone compound + Spironolactone; Cyproterone compound (Cyproterone acetate 2mg+Ethinyl estradiol 35 mcg) once daily + Spironolactone 50 mg twice daily	Drug: Cyproterone compound + Spironolactone; Cyproterone compound (Cyproterone Acetate 2mg-Ethinyl estradiol 35mcg) 1 tablet daily + Spironolactone 50 mg twice daily; Other Names: CC-S
Active Comparator: Metformin; Metformin 1500 mg daily	Drug: Metformin; Metformin 500mg three times daily
Active Comparator: Pioglitazone; Pioglitazone 30 mg daily	Drug: Pioglitazone; Pioglitazone 30mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum C3 level	Serum concentration of a component of complement cascade: C3	3 months
Serum C4 level	Serum concentration of a component of complement cascade: C4	3 months
Serum high-sensitive CRP (C-reactive protein)	Serum concentration of high-sensitive C-reactive protein (hs-CRP)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum total Testosterone level	Serum concentration of total Testosterone	3 months
Serum free Testosterone level	Serum concentration of free Testosterone	3 months
Serum Dehydroepiandrosterone sulfate (DHEAS) level	Serum concentration of Dehydroepiandrosterone sulfate	3 months
Serum follicle stimulating hormone (FSH) level	Serum concentration of follicle stimulating hormone	3 months
Serum luteinizing hormone (LH) level	Serum concentration of luteinizing hormone	3 months
Fasting Blood Sugar (FBS)	Fasting Blood Sugar	3 months
Fasting Serum Insulin level	Serum concentration of insulin	3 months
Serum homocysteine level	Serum concentration of homocysteine	3 months
Number of patients with adverse events	Number of patients with adverse events	3 months

Collaborators and Investigators

• Sponsor: Shiraz University of Medical Sciences
• Investigators: Principal Investigator: Mesbah Shams, MD, Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences; Study Chair: Gholamhossein R Omrani, MD, Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): December 30, 2018

Study Registration Dates

• First Submitted: February 19, 2016
• First Submitted That Met QC Criteria: February 23, 2016
• First Posted (Estimate): February 24, 2016

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 8, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Inflammation; Metformin; C-Reactive Protein; Ethinyl Estradiol; Homocysteine; Thiazolidinediones; Pioglitazone; Androgen Antagonists; Complement system proteins; Cyproterone
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Contraceptive Agents; Reproductive Control Agents; Androgen Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Contraceptive Agents, Male; Metformin; Pioglitazone; Spironolactone; Cyproterone Acetate; Cyproterone
• Other Study ID Numbers: CT-P-9145-4025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No