Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03981861

Enrollment

Registered

2019-06-11

Start date

2016-07-02

Completion date

2019-06-05

Last updated

2021-02-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

PCOS

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.

Interventions

DRUGMetformin and Spironolactone

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

13 Years to 21 Years

Healthy volunteers

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)

Design outcomes

Primary

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Treatment Treatment with Metformin and Spironolactone 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.	12
Total	12

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Treatment
Age, Continuous	16 years STANDARD_DEVIATION 1
Body Mass Index (BMI)	36.7 kg/m2 STANDARD_DEVIATION 10.9
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	8 Participants
Region of Enrollment North America	12 participants
Sex/Gender, Customized female	12 Participants
whole body insulin sensitivity index (WBISI)	3.67 μU/ml STANDARD_DEVIATION 4.39

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 12
other Total, other adverse events	0 / 12
serious Total, serious adverse events	0 / 12