Targeting Pathways in Polycystic Ovary Syndrome (PCOS) Using Metformin (MET)

Phase 1

Completed

• Conditions: Polycystic Ovary Syndrome
• Interventions: Drug: Metformin

• Registration Number: NCT02086526
• Lead Sponsor: Mayo Clinic

Brief Summary

The investigator's global hypothesis is that women with Polycystic Ovary Syndrome (PCOS) can be separated into subtypes based on their response to metformin. The investigators propose here to use both targeted and non-targeted metabolomic approach to identify pathways associated with metformin's effect on insulin sensitivity and endothelial function. This pilot project will be the foundation for developing tailored therapeutic approaches to Polycystic Ovary Syndrome and identifying novel drug targets.

Detailed Description

The investigators propose to use both targeted and non-targeted metabolomic approaches to identify pathways associated with metformin's effect on insulin sensitivity, weight, androgens and endothelial function. This project will be the foundation for developing tailored therapeutic approaches to Polycystic Ovary Syndrome and identifying novel drug targets. This pilot project is intended to inform the development of hypothesis and specific aims for a future grant application to National Institutes of Health (NIH).

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-03-11
• Study First Submitted QC: 2014-03-11
• Study First Posted: 2014-03-13
• Primary Completion: 2016-11-20
• Study Completion: 2016-11-20
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-15
• Last Update Posted: 2018-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 68

Inclusion Criteria

• Body mass index (BMI) greater than or equal to 25
• Polycystic Ovary Syndrome criteria of both oligomenorrhea (<9 menses per year) and androgen excess [clinical hirsutism (Ferriman-Gallway score >8 or severe acne) or elevated testosterone].
• Taking no medications for the treatment of insulin resistance.

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Exclusion Criteria

• Diagnosis of Cushing's syndrome
• Untreated hypo/hyperthyroidism
• Elevated prolactin
• Congenital adrenal hyperplasia
• Renal insufficiency (creatinine > 1.5)
• Diabetes
• Medications that can significantly affect endothelial function
• Pregnancy
• Breast Feeding
• Taking oral contraceptives
• Currently smoking

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	Metformin 500 mg. extended release (taken orally) one tablet with evening meal for one week, one tablet with morning and evening meal for one week, and one tablet at all three meals for the next three months.
Delayed Start Metformin	Metformin	After baseline study visit, this arm will return after three months without metformin for a repeat of the baseline study visit prior to initiating metformin 500 mg. extended release (taken orally) one tablet with evening meal for one week, one tablet with morning and evening meal for one week, and one tablet at all three meals for the next three months.

Primary Outcome Measures

Name	Time	Method
Change in Insulin Sensitivity (SI) after 3 Months of Metformin Therapy	Baseline, 3 months	Insulin sensitivity will be calculated using an oral glucose minimal model. Insulin under the curve will be calculated geometrically with the trapezoidal rule.

Secondary Outcome Measures

Name	Time	Method
Change in Peripheral Flow-Mediated Vasodilatation after 3 Months of Metformin Therapy	baseline, 3 months	The ratio of Peripheral Digital Arterial Tonometry (PAT) signal after cuff release compared with baseline is calculated through a computer algorithm normalizing for baseline measurements and indexing to measurements in the contra-lateral arm. The calculated ratio reflects the reactive hyperemia index (RHI).

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States