Clinical trial NCT06256289: Efficacy of Canagliflozin Versus Metformin in Women With Polycystic Ovary Syndrome
Official title: Efficacy of Canagliflozin Versus Metformin in Women With Polycystic Ovary Syndrome Combined With Non-Alcoholic Fatty Liver Disease: A Single-center, Open-labeled Prospective Randomized Controlled
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Polycystic Ovary Syndrome
Non-Alcoholic Fatty Liver Disease
Lead sponsor: The First Affiliated Hospital of Shanxi Medical University
Sponsor class: OTHER
First posted: 2024-02-13
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to investigate the use of ultra-high performance liquid chromatography-mass spectrometry for metabolomics and proteomics research in patients with Polycystic Ovary Syndrome (PCOS) and Non-Alcoholic Fatty Liver Disease (NAFLD). The main questions it aims to answer are:

* How can this technology help identify specific biomarkers for diagnosing PCOS combined with NAFLD?
* What is the role of Canagliflozin in improving the safety and efficacy of treatment for PCOS and NAFLD patients?

Participants, who are 50 non-diabetic women with PCOS, will undergo a series of assessments including cardiovascular metabolic indicators, liver NAFLD screening risk stratification, and insulin resistance index. They will be compared with 50 age and BMI-matched healthy controls. The participants will be randomized to receive either CANA/MET (Canagliflozin 100 mg daily plus Metformin 1000 mg twice daily) or MET (Metformin 1000 mg twice daily) for a continuous period of three months. The study will evaluate various parameters including menstrual patterns, anthropometric parameters, gonadal parameters, glucose-lipid homeostasis, liver enzyme indices, non-invasive hepatic fat changes, metabolomics, and NAFLD-related indicators.

Detailed description: Objective: 1. This study employs the latest ultra-high performance liquid chromatography-mass spectrometry platform for metabolomics and proteomics research to analyze serum samples from patients with Polycystic Ovary Syndrome (PCOS) coexisting with Non-Alcoholic Fatty Liver Disease (NAFLD). The aim is to identify specific biomarkers for the diagnosis of PCOS combined with NAFLD. At the same time, this study explores the pathogenesis and potential new therapeutic targets of PCOS combined with NAFLD at the protein and metabolic levels. 2. The study examines the role of Canagliflozin in improving the safety and efficacy of PCOS and NAFLD patients, providing evidence for the use of SGLT2 inhibitors as an effective treatment for PCOS with NAFLD.

Methods: The study enrolled 50 non-diabetic PCOS women and assessed cardiovascular metabolic indicators including liver NAFLD screening risk stratification, insulin resistance index, etc. These were compared with 50 age and BMI-matched healthy controls. Utilizing the latest ultra-high performance liquid chromatography-mass spectrometry platform for metabolomics and proteomics research, a diagnostic model for PCOS coexisting with NAFLD was established and evaluated. The 50 patients were randomized 1:1 to receive Canagliflozin/Metformin or Metformin treatment. The Canagliflozin/Metformin group received Canagliflozin 100 mg once daily plus metformin 1000 mg twice daily, and the metformin group received Metformin 1000 mg twice daily, for a continuous period of three months. The study assessed the safety and efficacy of PCOS and NAFLD patients.

Eligibility criteria: Inclusion Criteria:

1. aged 18-45 years old;
2. Body mass index (BMI) more than 18.5 kg / m2;
3. PCOS diagnosis meets Rotterdam 2003 criteria: at least two of the following symptoms: menstrual menstruation / amenorrhea, hyperandrogenism, and / or biochemical and / or clinical signs of polycystic ovaries.
4. The serum pregnancy test was negative before enrollment.
5. Clinical diagnosis of fatty liver: the ratio of liver to kidney is greater than 1.0.

Can understand the procedures and methods of this clinical trial, patients voluntarily participate and sign the informed consent form, willing to comply with the trial protocol requirements and cooperate with the provision of biological samples for testing as planned.

Exclusion Criteria:

1. Less than 18 years old or more than 45 years old;
2. Patients who are pregnant, intend to become pregnant, are breastfeeding or giving birth;
3. Drug history in the past three months included oral contraceptives, sodium-dependent glucose transporters 2 inhibitors, glucagon-like peptide-1 receptor agonists, thiazolidinediones, metformin, corticosteroids or traditional Chinese medicine.
4. Endocrine disorders such as hyperprolactinemia, thyroid dysfunction and diabetes, Cushing's syndrome, 21-hydroxylase deficiency, congenital adrenal hyperplasia, androgen-secreting tumors, cervical, endometrial or breast cancer.
5. Severe liver function (alanine aminase, aspartate aminase\> 3 times normal value or elevation of serum bilirubin to more than 3 times the upper limit of normal) or renal impairment (eGFR \<60 ml/min/1.73m2).Severe cardiopulmonary, hematopoietic and hematopoietic insufficiency.
6. Current or past (most recent three months) participation in other studies.
7. Viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis, hemochromatosis, anti-trypsin defense, Wilson disease, parenteral nutrition history, use of drugs known to cause steatosis (such as valproate, amiodarone or vitamin E) or liver injury caused by drug abuse.Clinical evidence of hepatic decompensation, such as hepatic encephalopathy, ascites, and variceal bleeding.
8. drank more than 20g per day.
9. Women with persistent or recurrent symptomatic urinary tract infections (UTI), gastrointestinal (GI) problems, or any other condition that may compromise patient safety had strong fertility needs within six months of the study period.
10. Allergic or intolerant to the study drug, unable to continue treatment as required by the protocol, unwilling to complete the study or become pregnant.
11. History of mental illness within 2 years, including any suicidal behavior or major depression, depressive symptoms (defined as Patient Health Questionnaire-9 score more than 15), central nervous system disease (including but not limited to any type of seizure or stroke), and no cognitive behavior (including the investigator considers poor adherence to evaluate efficacy or is unlikely to complete the intended course and follow-up).

Primary outcomes:
measure: liver steatosis index CAP (Controlled Attenuation Parameter) measured by FibroScan
timeFrame: at baseline and 12 weeks
Secondary outcomes:
measure: liver stiffness index (LS） measured by transient elastography, FibroScan
timeFrame: at baseline and 12 weeks
measure: Body Composition, including total body water, muscle mass, fat mass (subcutaneous and visceral), fat-free mass detected using Bioelectrical Impedance Analysis (BIA)
timeFrame: at baseline and 12 weeks
measure: selection of proteomics markers using liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry for analysis
timeFrame: at baseline and 12 weeks
measure: selection of metabolomics markers by by liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometryprecision
timeFrame: at baseline and 12 weeks
measure: sex hormones by liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry
timeFrame: at baseline and after 12 weeks
measure: Gut Microbiota diversity sequencing by 16s rRNA Amplicon Sequencing Analysis
timeFrame: at baseline and 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: The First Affiliated Hospital of Shanxi Medical University
name: Ping Li, MD
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital of Shanxi Medical University
name: Linxin Xu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Shanxi Medical University
name: Yan Wang
role: STUDY_DIRECTOR
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