Metformin, Vitamin D, and Depression in Polycystic Ovary Syndrome (PCOS) Trial

Study Overview
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Brief Summary
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Open-label randomized clinical trial assessing the efficacy of Metformin versus Vitamin D in improving symptoms of depressed mood in polycystic ovary syndrome.

Detailed Description
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This is a single center, open-label, randomized, pilot clinical trial. Women with polycystic ovary syndrome and depressed mood, who are insulin resistant and vitamin D insufficient are eligible. Subjects are randomly assigned to one of two interventions: Vitamin D versus metformin. Subjects are followed with questionnaires and a final wrap-up clinic visit with a physician. The study duration is 12 weeks.

Official Title
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Metformin, Vitamin D, and Depression in Polycystic Ovary Syndrome (PCOS) Trial: The MINDD Trial

Conditions
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PCOS, Depression, Vitamin D Deficiency, Insulin Resistance

Intervention / Treatment
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* Drug: Metformin
* Drug: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Polycystic Ovary Syndrome diagnosis (Rotterdam Criteria) Vitamin D insufficiency (serum Vitamin D <30 ng/mL) Insulin resistance Mild or greater severity of depression by Beck Depression Inventory-II Exclusion Criteria: Current metformin use Vitamin D supplementation of > 50,000 IU following confirmation of Vitamin D insufficiency Insulin-dependent diabetes mellitus Pregnancy or breastfeeding Untreated hypothyroidism Current active substance abuse Other major medical comorbidity: renal or hepatic dysfunction, severe pulmonary Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>Metformin 1000 mg PO bid | Drug: Metformin<br>* Oral medication daily<br>* Other names: Glumetza;|
| Experimental: Vitamin D (Cholecalciferol)<br>Cholecalciferol 5,000 IU PO daily | Drug: Vitamin D<br>* Oral medication daily<br>* Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Depression Score on the Beck Depression Inventory (BDI-II) at 12 Weeks | BDI-II is a validated self-reported instrument of 21 questions which are each scored 0-3. Total scores range from 0-63, with higher score totals indicating more severe depression symptoms. {0-9: indicates minimal depression; 0-18: indicates mild depression; 19-29: indicates moderate depression; 30-63: indicates severe depression}. Change = Week 12 total score - Baseline week score | Baseline & 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline Week in Insulin Resistance Score at Week 12. | Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) will be used to calculate Insulin Resistance based on fasting glucose (mg/dL) and fasting insulin (μIU/mL) blood serum assays tested at Quest Diagnostics. HOMA-IR = Fasting Insulin (uIU/mL) x Fasting Glucose (mg/dL). Healthy range is between 0.5-1.4. Values below 1.0 indicate insulin sensitivity and are optimal. Values greater than 1.9 indicate clinically significant insulin resistance. | Baseline week & week 12 | 
| Change From Baseline in State-Trait Anxiety Inventory Score (STAI-S) at 12 Weeks | STAI-S is a validated self-reported instrument of 20 questions. Range of scores for the State Anxiety (STAI-S) subtest is 20-80, the higher score indicating greater anxiety. A threshold point score of 39-40 has been suggested by recent literature to detect clinically significant symptoms. Change = Week 12 total score - Baseline week score | Baseline week & Week 12 | 
| Changes From Baseline Week in Vitamin D 25-hydroxy Levels at Week 12. | Vitamin D, 25-hydroxy blood serum assays will be tested at Quest Diagnostics. Changes in values from baseline week to week 12 will be calculated. Reference ranges: optimal 30-100 ng/mL Insufficient 20-29 ng/mL deficient <20ng/mL | Baseline week & week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, Depression, Vitamin D, Insulin Resistance, Anxiety, Quality of life, Mood disorders