Metformin for Ectopic Fat Deposition and Metabolic Markers in Polycystic Ovary Syndrome (PCOS)

NCT02500147 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: AAAF4452
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This project, "A double-blind placebo-controlled randomized clinical trial assessing the efficacy of metformin for hepatic fat in adolescents and young adults with polycystic ovary syndrome", proposes exploring the use of novel and noninvasive methodologies in an at-risk adolescent and young adult population with polycystic ovary syndrome (PCOS) who may gain long-term health benefits from early detection and treatment of non-alcoholic fatty liver disease (NAFLD). PCOS is a common condition that frequently presents in adolescence and young adulthood and is defined by elevated androgens (male hormones) in the blood leading to 1. hirsutism and acne and 2. menstrual abnormalities or amenorrhea. Affected individuals are at increased risk of developing insulin resistance (a precursor of diabetes), NAFLD and lipid (cholesterol) abnormalities.These features are all associated with the metabolic syndrome, a rising major public health concern. Recently, an association between PCOS and NAFLD has been noted but has only been superficially studied in the adolescent and young adult population. The susceptibility of certain PCOS patients to developing NAFLD is theorized to be due to having underlying insulin resistance, elevated androgen levels, and a genetic predisposition. Metformin is an insulin sensitizing medication widely used to treat type 2 diabetes mellitus that may have beneficial effects on insulin resistance-related conditions including PCOS and NAFLD. Although widely used in PCOS, its effect on NAFLD in this group has not been previously studied. The primary aims of this proposal are: 1) To determine whether PCOS with liver fat \>/=4.8% treated with metformin for six months will have a decline in percentage liver fat compared to a placebo group. 2) To measure the association of the PNPLA3 I148M allele with NAFLD in PCOS at baseline (n=40). 2b) To measure the association of percentage liver fat with biomarkers of NAFLD, dyslipidemia, insulin resistance and body composition at baseline (n=40) and after a placebo-controlled intervention with metformin in PCOS with liver fat \>4.8% (n=20). The goal of this research proposal is to explore the use of novel and noninvasive technologies in a young and at risk population. Dr. Sopher hopes to use the results of this research to lay the groundwork for the prevention and treatment of NAFLD and other metabolic disorders in adolescents and young adults with PCOS and to prevent lifelong morbidity associated with PCOS.

Conditions

Polycystic Ovary Syndrome; Non-Alcoholic Fatty Liver Disease; Metabolic Syndrome

Keywords

Polycystic Ovary Syndrome; Non-Alcoholic Fatty Liver Disease; Adolescents; Young Women; MRI; MRS; DXA; PNPLA3; Metformin; Randomized Clinical Trial; Placebo; Hirsutism; Acne; Amenorrhea; Metabolic Syndrome; Dyslipidemia; Percentage liver fat

Outcome Measures

Primary Outcomes (1)

• Percentage Liver Fat in Participants

  To compare percentage liver fat by magnetic resonance spectroscopy in the metformin group and placebo group to baseline and between the groups in order to determine if metformin is efficacious for reducing liver fat compared to placebo in adolescents and young women with Polycystic Ovary Syndrome (PCOS)

  6 months

Secondary Outcomes (1)

• The Association of Percentage Liver Fat by Magnetic Resonance Spectroscopy With Insulin Resistance as Measured by HOMA-IR in Adolescents With PCOS

  6 months

Other Outcomes (6)

• The Association of Percentage Liver Fat With M30, a Hepatic Apoptosis Marker

  6 months

• The Association of Percentage Liver Fat With Pancreatic Polypeptide

  6 months

• The Association of Percentage Liver Fat With Total Body Adipose Tissue

  6 months

Study Arms (2)

Metformin

EXPERIMENTAL

Adolescents and young adults with PCOS and liver fat greater than or equal to 4.8% will be randomized to metformin or placebo. Metformin ER (extended release) will be administered as two pills of 500 mg each. For the first week subjects will take one pill orally on a daily basis and thereafter will take two pills orally on a daily basis. The intervention will last six months.

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Adolescents and young adults with PCOS and liver fat greater than or equal to 4.8% will be randomized to metformin or placebo. Subjects randomized to placebo will be instructed to take one pill daily by mouth for one week and then to take one pill daily by mouth for the remainder of six months.

Drug: Placebo

Interventions

Metformin DRUG

Metformin ER 500 mg once a day for one week and 1000 mg once a day for the remainder of the six months

Also known as: Fortamet

Metformin

Placebo DRUG

One placebo pill per day for one week and then two placebo pills per day for the remainder of the six months

Also known as: Placebo pill

Placebo

Eligibility Criteria

• Age: 13 Years - 25 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Healthy adolescent girls and young women 13 - 25 years old
• At least 2 years postmenarche

You may not qualify if:

• Past or present history of a medical disorder or medication known to affect body composition
• Insulin secretion and sensitivity, or the GH-IGF-I axis (e.g. steroid hormone or thyroid replacement)
• Any diseases affecting bone metabolism (collagen disorders, primary hyperparathyroidism, nephrolithiasis, untreated hyperthyroidism) indwelling hardware
• History of current or past pregnancy
• Hormonal contraceptive or metformin use within 3 months of enrollment
• Nonclassical congenital adrenal hyperplasia (CAH) - early morning 17-hydroxyprogesterone level less than 200 ng/dL

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (2)

• Sopher AB, Grigoriev G, Laura D, Cameo T, Lerner JP, Chang RJ, McMahon DJ, Oberfield SE. Anti-Mullerian hormone may be a useful adjunct in the diagnosis of polycystic ovary syndrome in nonobese adolescents. J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1175-9. doi: 10.1515/jpem-2014-0128.

  PMID: 25003376 RESULT

• Sopher AB, Gerken AT, Blaner WS, Root JM, McMahon DJ, Oberfield SE. Metabolic manifestations of polycystic ovary syndrome in nonobese adolescents: retinol-binding protein 4 and ectopic fat deposition. Fertil Steril. 2012 Apr;97(4):1009-15. doi: 10.1016/j.fertnstert.2012.01.111. Epub 2012 Feb 17.

  PMID: 22341881 RESULT

Related Links

• Information about PCOS
• Information about NAFLD
• Information about metformin

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Non-alcoholic Fatty Liver Disease; Metabolic Syndrome; Hirsutism; Acne Vulgaris; Amenorrhea; Dyslipidemias

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hair Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Virilism; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Acneiform Eruptions; Sebaceous Gland Diseases; Menstruation Disturbances; Pathologic Processes; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Aviva B Sopher, MD, MS
• Organization: Columbia University

ahs32@cumc.columbia.edu

212-305-9362

Study Officials

• Aviva B Sopher, MD, MS, MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics, Dept Pediatrics Endocrinology

Study Record Dates

• First Submitted: July 7, 2015
• First Posted: July 16, 2015
• Study Start: September 8, 2011
• Primary Completion: March 3, 2021
• Study Completion: March 3, 2021
• Last Updated: July 2, 2025
• Results First Posted: July 2, 2025

Record last verified: 2025-06

Locations

US (1)