Efficacy of Canagliflozin Versus Metformin in Women With Polycystic Ovary Syndrome

February 4, 2024 updated by: Ping Li,MD

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: canagliflozin plus metformin group
canagliflozin 100 mg once daily plus metformin 1000 mg twice daily
Drug: Canagliflozin 100mg Tab
Canagliflozin 100mg once daily combined Metformin 1000mg twice daily
Other Names:
  • Invokana
Drug: Metformin Hydrochloride
Metformin 1000mg twice daily
Other Names:
  • Glucophage
Active Comparator: metformin group
metformin 1000 mg twice daily
Drug: Metformin Hydrochloride
Metformin 1000mg twice daily
Other Names:
  • Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
liver steatosis index CAP (Controlled Attenuation Parameter) measured by FibroScan
Time Frame: at baseline and 12 weeks
Changes in the liver steatosis index CAP (Controlled Attenuation Parameter) as measured by transient elastography after 12 weeks of treatment.
at baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
liver stiffness index (LS） measured by transient elastography, FibroScan
Time Frame: at baseline and 12 weeks
Changes in the liver stiffness index (LS) (measured by transient elastography) from baseline to 12 weeks of treatment.
at baseline and 12 weeks
Body Composition, including total body water, muscle mass, fat mass (subcutaneous and visceral), fat-free mass detected using Bioelectrical Impedance Analysis (BIA)
Time Frame: at baseline and 12 weeks
Changes in Body Composition，including total body water, muscle mass, fat mass (subcutaneous and visceral), fat-free mass detected using Bioelectrical Impedance Analysis (BIA) from baseline to 12 weeks of treatment.
at baseline and 12 weeks
selection of proteomics markers using liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry for analysis
Time Frame: at baseline and 12 weeks
Changes in proteomics markers from baseline to 12 weeks of treatment, involving systematic quantification of metabolites and proteins using techniques LC-MS for analysis, with chemometric methods for data interpretation, revealing metabolic pathways and biomarkers.
at baseline and 12 weeks
selection of metabolomics markers by by liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometryprecision
Time Frame: at baseline and 12 weeks
Changes in metabolomics markers from baseline to 12 weeks of treatment, including phosphatidylglycerol (PG), Bis(monoacylglycero)phosphate BMP, Sulfatide (sulfatide) (SL), Free fatty acids FFA, Plasmalogen ethanolamine (PE-O), Phosphatidylethanolamine (PE), Phosphatidylinositol (PI), Phosphatidylserine (PS), Monosialosyl ganglioside (GM3) plasmalogen (PCO), Phosphatidylcholine (PC), Lysophosphatidic acid (PA), Lysophosphatidylethanolamine (LPE), Lysophosphatidic acid (LPA), Lysophosphatidylinositol (LPI), Lysophosphatidylserine (LPS), Ceramide(Cer), Lysophosphatidylcholine （LPC), Plasmalogen choline (PCO), Phosphatidylcholine (PC),Sphingomyelin (SM),Sphingosine (Sph）,Ceramide（Cer）,Hexosylceramide （HexCer）, Lactosylceramide （LacCer）, Trihexosylceramide （Gb3), Acylcarnitine acylcarnitine, Monoacylglycerol (MAG), Diglyceride (DAG), Triglyceride (TAG), Cholesteryl ester (CE)
at baseline and 12 weeks
sex hormones by liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry
Time Frame: at baseline and after 12 weeks
Changes in sex hormones by liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry from baseline to 12 weeks of treatment, including estriol, hydrocortisone, cortisone, corticosterone, aldosterone, testosterone, 17a-Hydroxyprogesterone, 21-hydroxyprogesterone, DHEA,Estrone, androstenedione, dihydrotestosterone, estradiol,progesterone, pregnenolone, androsterone, epitestosterone, estrone sulfate, estradiol sulfate, epitestosterone sulfate, testosterone sulfate, dhea Sulfate, pregnenolone Monosulfate
at baseline and after 12 weeks
Gut Microbiota diversity sequencing by 16s rRNA Amplicon Sequencing Analysis
Time Frame: at baseline and 12 weeks
Gut microbiome testing equipment includes sterile samplers for sample collection, DNA extraction kits, PCR machines for amplification, high-throughput sequencing platforms for analysis, bioinformatics software for data processing, and AI systems for advanced analysis. These tools enable precise and efficient assessment of gut microbial composition, aiding in understanding its impact on disease and informing clinical treatments.
at baseline and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ping Li,MD

Investigators

  • Study Chair: Ping Li, MD, The First Affiliated Hospital of Shanxi Medical University
  • Principal Investigator: Linxin Xu, MD, The First Affiliated Hospital of Shanxi Medical University
  • Study Director: Yan Wang, The First Affiliated Hospital of Shanxi Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 31, 2024

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

April 30, 2025

Study Registration Dates

First Submitted

January 28, 2024

First Submitted That Met QC Criteria

February 4, 2024

First Posted (Estimated)

February 13, 2024

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 4, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FirstofShanxiMU

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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