Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

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.

Study Overview

• Status: Completed
• Conditions: PCOS
• Intervention / Treatment: Drug: Metformin and Spironolactone

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Overall Study; Treatment with Metformin and Spironolactone	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.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Children's Mercy Hospital Kansas City

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2016
• Primary Completion (Actual): July 9, 2018
• Study Completion (Actual): June 5, 2019

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 7, 2019
• First Posted (Actual): June 11, 2019

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 4, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Metformin; Spironolactone
• Other Study ID Numbers: 16010020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No