Clinical trial NCT02506946: NAFLD in Adolescents and Young Adults With PCOS
Official title: Nonalcoholic Fatty Liver Disease (NAFLD), Insulin Resistance and Dyslipidemia in Adolescents and Young Adults With Polycystic Ovary Syndrome (PCOS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Hirsutism
Amenorrhea
Metabolic syndrome
Dyslipidemia
Percentage liver fat
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2015-07-23
Enrollment: 80
Sex: FEMALE
Minimum age (years): 14
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy adolescent girls and young women 14 - 25 years with and without PCOS

Brief summary: This project focuses on an at-risk adolescent and young adult population who may gain long-term health benefits from detection of risk factors at a young age. The primary aims of this proposal are: 1) To observe whether adolescents and young adults with Polycystic Ovary Syndrome (PCOS) are more likely to have elevated liver fat (\>/=4.8%) than controls by studying liver fat deposition measured by magnetic resonance spectroscopy (MRS); 2) To assess the association of percentage liver fat with biomarkers of Non-alcoholic fatty liver disease (NAFLD), dyslipidemia, insulin resistance and body composition in PCOS and controls.

In the proposed study, 40 adolescents and young adults with PCOS and 40 age-comparable control subjects will be evaluated for metabolic disturbances and elevated liver fat using noninvasive and state-of-the-art techniques including MRI, dual-energy x-ray absorptiometry and an oral glucose tolerance test in order to fully assess the metabolic and body composition differences between these groups. This research proposal represents a critical step in understanding the metabolic and cardiovascular comorbidities of PCOS and their relationship to NAFLD. The investigator hopes to use the results generated by this research proposal in order to lay the groundwork for the prevention and treatment of metabolic disorders in adolescents with PCOS. The overarching goal is to decrease and prevent lifelong morbidity associated with this common disorder.

Detailed description: PCOS is a common condition that frequently presents in adolescence and young adulthood and is defined by the presence of hyperandrogenism and ovulatory dysfunction. Affected individuals are at increased risk of insulin resistance, NAFLD and dyslipidemia, which are features associated with the metabolic syndrome, a major public health concern. The associations between PCOS and both insulin resistance and dyslipidemia have been extensively described; however, its association with NAFLD has only recently been noted and superficially studied in adolescents and young adults. Additionally, it has not yet been fully elucidated why seemingly healthy nonobese adolescents with PCOS are predisposed to insulin resistance and its related complications. The susceptibility of certain PCOS patients to developing NAFLD is theorized to be due to the following potentiating factors: insulin resistance, hyperandrogenemia, and a genetic predisposition.

Eligibility criteria: Inclusion Criteria:

* All: Healthy; between 14 and 25 years; at least 2 years postmenarche
* PCOS: Clinical hyperandrogenism and/or hyperandrogenemia, menstrual dysfunction (oligomenorrhea or amenorrhea) and exclusion of other known disorders. PCOS will be diagnosed using the NIH 1990 criteria.
* Controls: Regular menses; no clinical hyperandrogenism and/or hyperandrogenemia

Exclusion Criteria:

* Past or present history of a medical disorder or medication known to affect body composition, insulin secretion and sensitivity, or the growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis (eg steroid hormone or thyroid replacement).
* History of current or past pregnancy
* Hormonal contraceptive or metformin use within 3 months of enrollment
* Nonclassical congenital adrenal hyperplasia

Primary outcomes:
measure: Difference in percentage liver fat between PCOS and controls in adolescents and young adults
timeFrame: 1 day
Secondary outcomes:
measure: The association of percentage liver fat by magnetic resonance spectroscopy with insulin resistance as measured by HOMA-IR.
timeFrame: 1 day
measure: The association of percentage liver fat by magnetic resonance spectroscopy with triglycerides
timeFrame: 1 day
measure: The association of percentage liver fat by magnetic resonance spectroscopy with visceral adipose tissue (VAT)
timeFrame: 1 day
measure: The association of percentage liver fat by magnetic resonance spectroscopy with total body adipose tissue
timeFrame: 1 day
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Aviva Sopher, MD, MS, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.