Clinical trial NCT05966792: SGLT2 Inhibitors in Treating Patients With PCOS
Official title: The Clinical Efficacy and Mechanism of SGLT2 Inhibitors Treating Polycystic Ovary Syndrome by Modulating the Nod-like Receptor Protein 3 Inflammasome
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Polycystic Ovary Syndrome
Lead sponsor: Shanghai 10th People's Hospital
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic inflammation is the core of Polycystic ovary syndrome (PCOS), and obesity and overweight further exacerbate the level of inflammation in the peripheral circulation and ovarian tissue in PCOS patients. Metformin is a classic endocrine drug for the treatment of PCOS, but its clinical response rate is only about 40%. Our previous published study (Diabetes Obes Metab, 2022) observed that the new hypoglycemic drug SGLT-2 inhibitor can significantly improve the clinical symptoms of patients with insulin resistance PCOS, and the clinical efficacy is not inferior to metformin, but its specific mechanism of action is not clear. Recent studies have shown that SGLT-2 significantly attenuates the activation of the Nod-like receptor protein 3 (NLRP3) inflammasomes and the secretion of IL-1β in patients with type 2 diabetes mellitus at high risk of cardiovascular disease. Based on the above research background, this project will combine clinical research and mechanism exploration to solve the following two problems:

1. whether SGLT2 inhibitor can further improve the clinical efficacy of PCOS patients compared to metformin;
2. mechanistic studies further clarify whether SGLT2 inhibitors improve inflammatory symptoms by modulating NLRP3 inflammosomes in the treatment of polycystic ovary syndrome;

Detailed description: This clinical study is a prospective, single-center, randomized (1:1) controlled clinical study. The enrollment population is overweight or obese PCOS patients. After signing the informed consent form, patients who meet the inclusion/exclusion criteria will be randomly assigned to the experimental and control groups for treatment in a 1:1 ratio, for a total of 108 patients enrolled.

Subjects randomized to the trial group will receive SGLT-2 inhibitors for 24 weeks.

Participants randomised to control will receive metformin for 24 weeks.

Eligibility criteria: Inclusion Criteria:

* Female aged 18-45
* Meet Rotterdam criteria
* BMI≥20kg/m2

Exclusion Criteria:

* Treatment with any additional medications that might impede the trial, including GLP-1 RAs, metformin, pioglitazone, contraceptives, or traditional Chinese medicine within the past 3 months
* Pregnancy or lactation
* Mental illness
* Malignant tumors
* Chronic kidney disease or severe liver dysfunction
* Inflammatory bowel disease
* Involvement in other research programs within the past 3 months

Primary outcomes:
measure: Menstrual cycles
timeFrame: 6 months
Secondary outcomes:
measure: HOMA-IR
timeFrame: 6 months
measure: NLRP3
timeFrame: 6 months
measure: IL-1β
timeFrame: 6 months
measure: IL-18
timeFrame: 6 months
measure: LH
timeFrame: 6 months
measure: FSH
timeFrame: 6 months
measure: PRL
timeFrame: 6 months
measure: E2
timeFrame: 6 months
measure: P
timeFrame: 6 months
measure: TT
timeFrame: 6 months
measure: AMH
timeFrame: 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Tenth People'S Hospital
state: Shanghai
Study officials:
affiliation: Shanghai 10th People's Hospital
name: Manna Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
References: