Dapagliflozin Efficacy and Action in PCOS

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of dapagliflozin on improving insulin resistance and hyperandrogenemia in obesity women with polycystic ovary syndrome.

Official Title
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Efficacy and Safety of Dapagliflozin in Polycystic Ovary Syndrome: a Multicentre, Randomized, Placebo-controlled Trial

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women aged 18 to 45 years; Subjects with PCOS diagnosed by according to the Rotterdam criteria; BMI ≥24 kg/m2 and/ or Homeostatic model assessment of insulin resistance (HOMA-IR) with a cutoff ≥2.5; No pregnancy plan within the next 6 months; Exclusion Criteria: Congenital adrenal hyperplasia such as 21-hydroxylase deficiency, hyperprolactinemia, Cushing syndrome, androgen-producing tumors of the adrenal gland or ovary; Other endocrine diseases include poorly controlled thyroid diseases (hyperthyroidism or hypothyroidism), acromegaly, type 2 diabetes; Patients with a history of acute / chronic infection, severe cardio-cerebrovascular diseases and acute / chronic pancreatitis; Taking any antidiabetic medication that would affect insulin resistance or hyperandrogenemia (i.e. TZD, GLP-1RA, DPP-4i, metformin) in the past one month; Taking letrozole, clomiphene, oral contraceptive, glucocorticoid, gonadotropin, gonadotropin releasing hormone agonist, anti-androgen drug (spironolactone, cycloproterenone acetate, Flutamide etc.) and/or other drugs for PCOS in the past three months; History of recurrent urinary tract infection; History of malignant tumor; Currently participating in weight loss programs or weight change in the past 3 months (> 5% current body weight) or have a history of gastrointestinal surgery. Serious liver dysfunction or chronic kidney disease (AST or ALT > 3 times the upper limit of normal, or eGFR<30 ml/min/1.73 m2); Women who are pregnant or plan to become pregnant; Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may affect the interpretation of efficacy or safety data; Participation in other clinical trial in the 4 weeks before randomization; Patients who are unwilling or unable to give informed consent.

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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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Dapagliflozin (Participants will receive dapagliflozin 10mg po qd). | Drug: Dapagliflozin<br>* Participants will receive dapagliflozin 10mg po qd. Additionally, participants will receive lifestyle modification and nutrition education.<br>|
| Placebo Comparator: Placebo<br>Placebo (Participants will receive placebo po qd) | Drug: Placebo<br>* Participants will receive placebo po qd. Additionally, participants will receive lifestyle modification and nutrition education.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in insulin resistance over 12 weeks | Change in insulin resistance assessed by insulin sensitivity index(HOMA-IR) | Baseline and 12 weeks | 
| Improvement in serum androgen level over 12 weeks | Change in androgen level assessed by free testosterone index(FAI) | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AUC (area under a curve) of glucose and insulin during the oral glucose tolerant test (OGTT) |  | Baseline to 12 week | 
| Change in serum free testosterone(FT) |  | Baseline to 12 week | 
| Change in serum sex hormone binding globulin(SHBG) |  | Baseline to 12 week | 
| Net change in total testosterone (TT) level |  | Baseline and 12 weeks | 
| Net change in dehydroepiandrosterone-sulfate(DHEAS) level |  | Baseline and 12 weeks | 
| Net change in androstenedione(AD) level |  | Baseline and 12 weeks | 
| Net change in luteinzing hormone(LH) level |  | Baseline and 12 weeks | 
| Net change in waist circumference |  | Baseline to 12 week | 
| Net Change in liver fat | Liver fat will be assessed by liver fibroscan. | Baseline to 12 week | 
| Change in ovulation rate assessed by serum progesterone |  | Baseline to 12 week | 
| Net change in body weight |  | Baseline to 12 week | 
| Net change in BMI |  | Baseline to 12 week | 
| Net change in glucose |  | Baseline to 12 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic Ovary Syndrome, SGLT2 inhibitor