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

• Sponsor: Shiraz University of Medical Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT02689843
• Collaborator: (none)
• Enrollment: 90
• Location: 1
• Arms: 3
• Actual Duration (Months): 10.9
• Patients Per Site Per Month: 8.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Drug: Cyproterone compound + Spironolactone; Drug: Metformin; Drug: Pioglitazone	Early Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Treatment With Cyproterone Compound-spironolactone, Metformin and Pioglitazone on Serum Inflammatory Markers in Patients With Polycystic Ovary Syndrome (PCOS)
• Actual Study Start Date: Feb 1, 2018
• Actual Primary Completion Date: Nov 30, 2018
• Actual Study Completion Date: Dec 30, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Serum C3 level [3 months]

   Serum concentration of a component of complement cascade: C3

2. Serum C4 level [3 months]

   Serum concentration of a component of complement cascade: C4

3. Serum high-sensitive CRP (C-reactive protein) [3 months]

   Serum concentration of high-sensitive C-reactive protein (hs-CRP)

Secondary Outcome Measures

1. Serum total Testosterone level [3 months]

   Serum concentration of total Testosterone

2. Serum free Testosterone level [3 months]

   Serum concentration of free Testosterone

3. Serum Dehydroepiandrosterone sulfate (DHEAS) level [3 months]

   Serum concentration of Dehydroepiandrosterone sulfate

4. Serum follicle stimulating hormone (FSH) level [3 months]

   Serum concentration of follicle stimulating hormone

5. Serum luteinizing hormone (LH) level [3 months]

   Serum concentration of luteinizing hormone

6. Fasting Blood Sugar (FBS) [3 months]

   Fasting Blood Sugar

7. Fasting Serum Insulin level [3 months]

   Serum concentration of insulin

8. Serum homocysteine level [3 months]

   Serum concentration of homocysteine

9. Number of patients with adverse events [3 months]

   Number of patients with adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shahid Motahhari Clinic, Shiraz University of Medical Sciences	Shiraz	Fars	Iran, Islamic Republic of

Sponsors and Collaborators

• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mesbah Shams, MD, Associate professor of internal medicine and endocrinology, Shiraz University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT02689843
• Other Study ID Numbers: CT-P-9145-4025
• First Posted: Feb 24, 2016
• Last Update Posted: Nov 12, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mesbah Shams, MD, Associate professor of internal medicine and endocrinology, Shiraz University of Medical Sciences: Inflammation; Complement system proteins; Homocysteine; C-Reactive Protein; Cyproterone; Ethinyl Estradiol; Androgen Antagonists; Metformin; Thiazolidinediones; Pioglitazone
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Syndrome; Metformin; Pioglitazone; Cyproterone Acetate; Spironolactone; Cyproterone

Study Results

No Results Posted as of Nov 12, 2019