Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

NCT ID: NCT03981861

Last Updated: 2021-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-02
• Study Completion Date: 2019-06-05

Brief Summary

To exam in the effect of a combination of low dose Metformin and Spironolactone on functional brain MRI, menstrual regulation and metabolism in adolescents with PCOS.

Detailed Description

Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in adolescent females and also one of the most complex. Patients experience an exaggerated ovarian/adrenal androgen production in response to physiologic and supra-physiologic elevations in insulin. The hormonal dysregulation is not only associated with acne, hirsutism, and menstrual irregularity, but also with perpetuated insulin resistance, central adiposity, and clinical depression.

In the proposed study, we aim to treat a hormonally and metabolically well-defined group of adolescent girls with PCOS with a combination of two pharmacological agents: metformin (insulin sensitizer) and spironolactone (anti-androgen) for 6 months. Although hyperandrogenism is a fundamental component of PCOS and responsible for the perpetuation of insulin resistance, adiposity and anovulation, there are few pediatric studies that have examined the benefits of treating both insulin resistance and hyperandrogenism simultaneously. Preliminary studies in adults, however, suggest synergistic effect of both spironolactone and metformin (spiro-met) with near normalization of the metabolic and ovulatory dysfunction. Therefore, we hypothesize that spiro-met will improve adolescent metabolism, body composition, ovarian morphology/function. We anticipate that our study will generate key pilot data for further randomized, double blind placebo controlled trials using both agents.

We also plan to examine functional brain MRI before and after the spiro-met intervention. This will allow us to inspect the effects of the hyperinsulinemic/androgenic hormonal milieu in PCOS on structural and functional brain MRI. We hypothesis, that the hormonal environment in PCOS affects centers of appetite and mood.

Conditions

PCOS

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Overall Study

Treatment with Metformin and Spironolactone

Group Type: EXPERIMENTAL

Metformin and Spironolactone

Intervention Type: DRUG

Oral Metformin tablet (500 mg/tablet) twice daily for 6 months. Oral Spironolactone tablet (50 mg/tablet) once daily for 6 months.

Interventions

Metformin and Spironolactone

Oral Metformin tablet (500 mg/tablet) twice daily for 6 months. Oral Spironolactone tablet (50 mg/tablet) once daily for 6 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Generally healthy
• Meeting Androgen Excess Society (AES) diagnostic criteria of PCOS: Menstrual Dysfunction or PCO ovaries on ultrasound AND clinical or biochemical hyperandrogenism
• Normal liver and kidney function
• No chronic illnesses except for stable, treated hypothyroidism

Exclusion Criteria

• Use of metformin and/or spironolactone within the last 6 months
• Currently on either oral hormonal contraception or other forms of hormonal contraception such as Depo-Provera, NuvaRing
• Current or past pregnancy
• Currently sexually active
• Psychiatric disorder based on self/parental report
• Type 2 diabetes (blood glucose > 200mg/dl on OGTT)
• Anemia (Hct < 35)
• Impaired kidney function (Baseline creatinine > 1.0 mg)
• Abnormal liver transaminases > 2 x the upper limit of normal range
• Potassium elevated outside the reference range (in non-hemolyzed blood sample)

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Children's Mercy Hospital Kansas City

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tania Burgert, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Mercy Hospital Kansas City

Locations

Children's Mercy Hospital

Kansas City, Missouri, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

16010020

Identifier Type: -

Identifier Source: org_study_id