Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents

• Sponsor: Children's Mercy Hospital Kansas City (Other)
• Overall Status: Completed
• CT.gov ID: NCT03981861
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 35.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
PCOS	Drug: Metformin and Spironolactone	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents
• Actual Study Start Date: Jul 2, 2016
• Actual Primary Completion Date: Jul 9, 2018
• Actual Study Completion Date: Jun 5, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Oral Glucose Tolerance Test [Change Measures: Baseline & 6 Months]

   Measurement of glucose and insulin at baseline and 2 hours after 75g of glucola.

2. Total Testosterone [Change Measures: Baseline & 6 Months]

   Total Testosterone measured in ng/dL

3. Free Testosterone [Change Measures: Baseline & 6 Months]

   Free Testosterone measured in ng/dL

4. Dehydroepiandrosterone Sulfate (DHEAS) [Change Measures: Baseline & 6 Months]

   DHEAS measured in mcg/dL

5. Body Mass Index (BMI) [Change Measures: Baseline & 6 Months]

   Body Mass Index measured in kg/m2

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 21 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Mercy Hospital	Kansas City	Missouri	United States	64108

Sponsors and Collaborators

• Children's Mercy Hospital Kansas City

Investigators

• Principal Investigator: Tania Burgert, MD, Children's Mercy Hospital Kansas City

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 17, 2019

More Information

Publications

None provided.

• Responsible Party: Children's Mercy Hospital Kansas City
• ClinicalTrials.gov Identifier: NCT03981861
• Other Study ID Numbers: 16010020
• First Posted: Jun 11, 2019
• Last Update Posted: Feb 23, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Metformin; Spironolactone

Study Results

Participant Flow

Arm/Group Title	Overall Study
Arm/Group Description	The pilot study was a non-controlled open label drug intervention study in a sample of adolescent girls attending a polycystic ovary syndrome (PCOS) clinic. Subjects received 6 months combination drug therapy with a combination of low dose metformin and spironolactone.
Period Title: Overall Study
STARTED	12
COMPLETED	9
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	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.
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16 (1)
Sex/Gender, Customized (Count of Participants)
female	12 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 16.7%
Not Hispanic or Latino	10 83.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 25%
White	8 66.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
North America	12 100%
whole body insulin sensitivity index (WBISI) (μU/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μU/ml]	3.67 (4.39)
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	36.7 (10.9)

Outcome Measures

1. Primary Outcome

Title	Oral Glucose Tolerance Test
Description	Measurement of glucose and insulin at baseline and 2 hours after 75g of glucola.
Time Frame	Change Measures: Baseline & 6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study
Arm/Group Description	This was a pilot non-controlled open label drug intervention study in a sample of adolescent girls attending a polycystic ovary syndrome (PCOS) clinic. Subjects received 6 months combination drug therapy with a combination of low dose metformin and spironolactone.
Measure Participants	9
Mean (Standard Deviation) [mg/dL]	0.9 (2.9)

2. Primary Outcome

Title	Total Testosterone
Description	Total Testosterone measured in ng/dL
Time Frame	Change Measures: Baseline & 6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study
Arm/Group Description	This was a pilot non-controlled open label drug intervention study in a sample of adolescent girls attending a polycystic ovary syndrome (PCOS) clinic. Subjects received 6 months combination drug therapy with a combination of low dose metformin and spironolactone.
Measure Participants	9
Mean (Standard Deviation) [ng/dL]	-12.57 (11.35)

3. Primary Outcome

Title	Free Testosterone
Description	Free Testosterone measured in ng/dL
Time Frame	Change Measures: Baseline & 6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study
Arm/Group Description	This was a pilot non-controlled open label drug intervention study in a sample of adolescent girls attending a polycystic ovary syndrome (PCOS) clinic. Subjects received 6 months combination drug therapy with a combination of low dose metformin and spironolactone.
Measure Participants	9
Mean (Standard Deviation) [ng/dL]	-0.15 (0.24)

4. Primary Outcome

Title	Dehydroepiandrosterone Sulfate (DHEAS)
Description	DHEAS measured in mcg/dL
Time Frame	Change Measures: Baseline & 6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study
Arm/Group Description	This was a pilot non-controlled open label drug intervention study in a sample of adolescent girls attending a polycystic ovary syndrome (PCOS) clinic. Subjects received 6 months combination drug therapy with a combination of low dose metformin and spironolactone.
Measure Participants	9
Mean (Standard Deviation) [mcg/dL]	-25.89 (79.07)

5. Primary Outcome

Title	Body Mass Index (BMI)
Description	Body Mass Index measured in kg/m2
Time Frame	Change Measures: Baseline & 6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Overall Study
Arm/Group Description	This was a pilot non-controlled open label drug intervention study in a sample of adolescent girls attending a polycystic ovary syndrome (PCOS) clinic. Subjects received 6 months combination drug therapy with a combination of low dose metformin and spironolactone.
Measure Participants	9
Mean (Standard Deviation) [kg/m2]	-1.3 (0.6)

Adverse Events

Time Frame	adverse event data was collected for the duration of the subject's intervention: 6 months
Adverse Event Reporting Description	Metformin is not known to cause death or hospitalization.
Arm/Group Title	Overall Study
Arm/Group Description	The pilot study was a non-controlled open label drug intervention study in a sample of adolescent girls attending a polycystic ovary syndrome (PCOS) clinic. Subjects received 6 months combination drug therapy with a combination of low dose metformin and spironolactone.
All Cause Mortality
	Overall Study
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	Overall Study
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Overall Study
	Affected / at Risk (%)	# Events
Total	0/12 (0%)

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed; Technical problems with measurement leading to unreliable or uninterpretable data. Study was not published for this reason.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.