Clinical trial NCT03981861: Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents
Official title: Metabolic and Neuro-Endocrine Effect of Treating PCOS in Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: PCOS
Lead sponsor: Children's Mercy Hospital Kansas City
Sponsor class: OTHER
First posted: 2019-06-11
Enrollment: 12
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Oral Glucose Tolerance Test
timeFrame: Change Measures: Baseline & 6 Months
measure: Total Testosterone
timeFrame: Change Measures: Baseline & 6 Months
measure: Free Testosterone
timeFrame: Change Measures: Baseline & 6 Months
measure: Dehydroepiandrosterone Sulfate (DHEAS)
timeFrame: Change Measures: Baseline & 6 Months
measure: Body Mass Index (BMI)
timeFrame: Change Measures: Baseline & 6 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
Study officials:
affiliation: Children's Mercy Hospital Kansas City
name: Tania Burgert, MD
role: PRINCIPAL_INVESTIGATOR
References: