Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

PCOS Clinical Trial

Official title:

Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03981861
• Other study ID #: 16010020
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2, 2016
• Est. completion date: June 5, 2019

Study information

• Verified date: February 2021
• Source: Children's Mercy Hospital Kansas City
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 5, 2019
• Est. primary completion date: July 9, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 13 Years to 21 Years

Eligibility

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)

Related Conditions & MeSH terms

• PCOS

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Children's Mercy Hospital	Kansas City	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Children's Mercy Hospital Kansas City

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oral Glucose Tolerance Test	Measurement of glucose and insulin at baseline and 2 hours after 75g of glucola.	Change Measures: Baseline & 6 Months
Primary	Total Testosterone	Total Testosterone measured in ng/dL	Change Measures: Baseline & 6 Months
Primary	Free Testosterone	Free Testosterone measured in ng/dL	Change Measures: Baseline & 6 Months
Primary	Dehydroepiandrosterone Sulfate (DHEAS)	DHEAS measured in mcg/dL	Change Measures: Baseline & 6 Months
Primary	Body Mass Index (BMI)	Body Mass Index measured in kg/m2	Change Measures: Baseline & 6 Months