SGLT2 Inhibitors in Treating Patients With PCOS

Polycystic Ovary Syndrome Clinical Trial

Official title:

The Clinical Efficacy and Mechanism of SGLT2 Inhibitors Treating Polycystic Ovary Syndrome by Modulating the Nod-like Receptor Protein 3 Inflammasome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05966792
• Other study ID #: SGLT2i in PCOS
• Status: Recruiting
• Phase: Phase 4
• Start date: November 10, 2023
• Est. completion date: March 15, 2025

Study information

• Verified date: June 2024
• Source: Shanghai 10th People's Hospital
• Contact: Manna Zhang, PhD
• Phone: +8613774448495
• Email: mannazhang[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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;

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: March 15, 2025
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Female aged 18-45

• Meet Rotterdam criteria

• Insulin resistance

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

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• SGLT2 inhibitors
Sodium-glucose cotransporters inhibitors (SGLT2i) are novel hypoglycemic drugs with unique hypoglycemic mechanisms, which are completely independent of islet ß-cell function or insulin sensitivity. Previous studies have shown that SGLT2i may improve IR by inhibiting glucotoxicity, reducing body weight, reducing inflammation, improving islet ß-cell function, and reducing oxidative stress.
• metformin
Metformin is a classic drug for the treatment of polycystic ovary syndrome, which can improve the degree of insulin resistance in PCOS patients.

Locations

Country	Name	City	State
China	Shanghai Tenth People'S Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai 10th People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Menstrual cycles	annual number of menstrual cycles	6 months
Secondary	HOMA-IR	Homeostatic model assessment insulin resistance index	6 months
Secondary	NLRP3	Nod-like receptor protein 3	6 months
Secondary	IL-1ß	Interleukin-1 beta	6 months
Secondary	IL-18	Interleukin-18	6 months
Secondary	LH	luteinizing hormone	6 months
Secondary	FSH	follicle-stimulating hormone	6 months
Secondary	PRL	prolactin	6 months
Secondary	E2	estradiol	6 months
Secondary	P	progesterone	6 months
Secondary	TT	total testosterone	6 months
Secondary	AMH	antimullerian hormone antimullerian hormone antimullerian hormone antimullerian hormone	6 months