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

Targeting Pathophysiologic Pathways in Polycystic Ovary Syndrome Using a Response to Metformin Phenotype

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.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Metformin

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 Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Metformin; Approximately 37 patients will start metformin therapy 3 months after their visit 2. All other patients will receive metformin therapy at their visit 2.; Other Names: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet
Other: Delayed Start 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.	Drug: Metformin; Approximately 37 patients will start metformin therapy 3 months after their visit 2. All other patients will receive metformin therapy at their visit 2.; Other Names: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peripheral Flow-Mediated Vasodilatation after 3 Months of Metformin Therapy	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).	baseline, 3 months

Other Outcome Measures

Outcome Measure	Time Frame
Change in Weight	baseline, 3 months
Change in Testosterone	baseline, 3 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Abbott Medical Devices
• Investigators: Principal Investigator: Alice Chang, MD, Mayo Clinic

Publications and helpful links

General Publications

• Heidari B, Lerman A, Lalia AZ, Lerman LO, Chang AY. Effect of Metformin on Microvascular Endothelial Function in Polycystic Ovary Syndrome. Mayo Clin Proc. 2019 Dec;94(12):2455-2466. doi: 10.1016/j.mayocp.2019.06.015.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): November 20, 2016
• Study Completion (Actual): November 20, 2016

Study Registration Dates

• First Submitted: March 11, 2014
• First Submitted That Met QC Criteria: March 11, 2014
• First Posted (Estimate): March 13, 2014

Study Record Updates

• Last Update Posted (Actual): March 19, 2018
• Last Update Submitted That Met QC Criteria: March 15, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• 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; Metformin
• Other Study ID Numbers: 13-000692; UL1TR000135 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes