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Semaglutide Improves Metabolic Abnormalities and Fertility in Obese Infertile Women With Polycystic Ovary Syndrome

Primary Purpose

PCOS (Polycystic Ovary Syndrome), Semaglutide

Status

Not yet recruiting

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Metformin Hydrochloride 500 MG

Semaglutide, 1.34 mg/mL

Semaglutide, 1.34 mg/mL and Metformin Hydrochloride 500 MG

calorie-restricted diet

physical exercise

About this trial

This is an interventional treatment trial for PCOS (Polycystic Ovary Syndrome) focused on measuring PCOS, semaglutide, obese, metabolic abnormality, fertility

Eligibility Criteria

22 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Meet the PCOS diagnostic criteria (Rotterdam） Age 22-40 BMI ≥ 28 kg/m2 Infertility: having normal sexual life and failing to conceive without contraception for more than 1 year Willing to be pregnant, and her husband has no serious infertility Exclusion Criteria: History of acute pancreatitis, individual or family history of medullary thyroid cancer and multiple endocrine adenomas Type 1 diabetes and special type diabetes History of tumor Serious cardiovascular and cerebrovascular disease, mental disease, liver or kidney disease Metformin, GLP-1 RA and other drugs affecting reproductive and metabolic functions were used within 90 days before the study Known allergy to metformin, GLP-1 RA and excipients Severe endometriosis, low ovarian reserve, premature ovarian failure Inability to tolerate pregnancy and ovulation induction therapy Other conditions considered unsuitable for this study by researchers

Sites / Locations

PekingUFH

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

metformin

semaglutide

semaglutide and metformin

Arm Description

About 25 subjects will be allocated to this group to receive metformin only, as the active comparator of semaglutide groups. Metformin used in this trial is Glucophage ( 500mg per tablet）produced by Bristol-Myers Squibb.The initial dose of metformin will be 500mg twice daily, which will be increased to 1000mg twice daily after two weeks, and then maintained until the end of treatment in total 12 weeks.

About 25 subjects will be allocated to this group to receive semaglutide only, as one of the experimental groups. Semaglutide used in this trial is WEGOVY (semaglutide) injection produced by Novo Nordisk. Administer WEGOVY once weekly, on the same day each week, at any time of day, with or without meals. Inject subcutaneously in the abdomen, thigh or upper arm. Initiate at 0.25 mg once weekly for 4 weeks. In 4 week intervals, increase the dose until a dose of 1.0 mg is reached, and then maintained 1.0 mg until the end of treatment in total 12 weeks..

About 25 subjects will be allocated to this group to receive both semaglutide and metformin, as another of the experimental groups. Metformin used in this trial is Glucophage ( 500mg per tablet）produced by Bristol-Myers Squibb.The initial dose of metformin will be 500mg twice daily, which will be increased to 1000mg twice daily after two weeks, and then maintained until the end of treatment in total 12 weeks. Semaglutide used in this trial is WEGOVY (semaglutide) injection produced by Novo Nordisk. Administer WEGOVY once weekly, on the same day each week, at any time of day, with or without meals. Inject subcutaneously in the abdomen, thigh or upper arm. Initiate at 0.25 mg once weekly for 4 weeks. In 4 week intervals, increase the dose until a dose of 1.0 mg is reached, and then maintained 1.0 mg until the end of treatment in total 12 weeks.

Outcomes

Primary Outcome Measures

Percentage change in bodyweight at 12 weeks for semaglutide versus metformin

Difference between body weight at 12 weeks and baseline divided by baseline body weight

Achievement of weight reduction of at least 5% at 12 weeks for semaglutide versus metformin

Proportion of patients with weight loss at least 5% at 12 weeks of treatment

Secondary Outcome Measures

HOMA-IR at 12 weeks of treatment

compare HOMA-IR at 12 weeks of treatment among three groups

testosterone level at 12 weeks of treatment

compare testosterone level at 12 weeks of treatment among three groups

androstenedione level at 12 weeks of treatment

compare androstenedione level at 12 weeks of treatment among three groups

FAI (Free Androgen Index) at 12 weeks of treatment

compare FAI at 12 weeks of treatment among three groups

Full Information

NCT ID

NCT05702905

First Posted

December 23, 2022

Last Updated

March 28, 2023

Sponsor

Peking University First Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05702905

Brief Title

Semaglutide Improves Metabolic Abnormalities and Fertility in Obese Infertile Women With Polycystic Ovary Syndrome

Official Title

Semaglutide Improves Metabolic Abnormalities and Fertility in Obese Infertile Women With Polycystic Ovary Syndrome: a Prospective, Randomized, Open, Controlled Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 2023 (Anticipated)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University First Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

To investigate the efficacy of semaglutide in obese infertile women of childbearing age with polycystic ovary syndrome (PCOS), we design this prospective, randomized, open and controlled study. 75 obese infertile PCOS patients will be recruited and randomized into three groups: metformin, semaglutide and metformin+semaglutide, on the basis of calorie-restricted diet and physical exercise. All subjects will be treated for 12 weeks, and then stop taking the drug for at least 8 weeks to initiate ovulation induction or ovulation induction combined with artificial insemination. All subjects will be followed up for 24 weeks for pregnancy outcome. The primary endpoint of the study is the percentage of weight loss at 12 weeks of treatment. The secondary endpoints include HOMA-IR and androgen levels at 12 weeks of treatment, ovulation rate at 24 weeks of follow-up, clinical pregnancy rate and cumulative pregnancy rate, and depression, anxiety, diet and quality of life scores at 12 weeks of treatment.

Detailed Description

To investigate the efficacy of semaglutide in obese infertile women of childbearing age with polycystic ovary syndrome (PCOS), we design this prospective, randomized, open and controlled study. 75 obese infertile PCOS patients will be recruited and randomized into three groups: metformin, semaglutide and metformin+semaglutide, on the basis of calorie-restricted diet and physical exercise. Metformin and semaglutide will be administered in a dose increasing mode, and then maintain until the end of 12 weeks, and metabolic related indexes will be evaluated. After 12 weeks of treatment, all subjects will stop taking the drug for at least 8 weeks to initiate ovulation induction or ovulation induction combined with artificial insemination. All subjects will be followed up for 24 weeks to evaluate the fertility related indicators. The primary endpoint of the study is the percentage of weight loss at 12 weeks of treatment. The secondary endpoints include HOMA-IR and androgen levels at 12 weeks of treatment, ovulation rate at 24 weeks of follow-up, clinical pregnancy rate and cumulative pregnancy rate, and depression, anxiety, diet and quality of life scores at 12 weeks of treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

PCOS (Polycystic Ovary Syndrome), Semaglutide

Keywords

PCOS, semaglutide, obese, metabolic abnormality, fertility

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

All subjects will be randomized into three groups: metformin single, semaglutide single, both metformin and semaglutide.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

metformin

Arm Type

Active Comparator

Arm Description

Arm Title

semaglutide

Arm Type

Experimental

Arm Description

Arm Title

semaglutide and metformin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Metformin Hydrochloride 500 MG

Other Intervention Name(s)

Glucophage

Intervention Description

Metformin oral tablet (500mg per tablet) will be administered in a dose increasing mode: the initial dose will be 500mg twice daily, which will be increased to 1000mg twice daily after two weeks, and then maintained until the end of treatment in total 12 weeks.

Intervention Type

Drug

Intervention Name(s)

Semaglutide, 1.34 mg/mL

Other Intervention Name(s)

WEGOVY

Intervention Description

Inject semaglutide subcutaneously once weekly, on the same day each week, at any time of day, in a dose increasing mode: the initial dose of 0.25mg QW (once a week), increased to 0.5mg QW after 4 weeks, and increased to 1.0mg QW after another 4 weeks, and then maintained 1.0mg until the end of treatment in total 12 weeks.

Intervention Type

Drug

Intervention Name(s)

Semaglutide, 1.34 mg/mL and Metformin Hydrochloride 500 MG

Other Intervention Name(s)

WEGOVY and Glucophage

Intervention Description

Both Semaglutide injection and Metformin oral tablet will be administered as described above.

Intervention Type

Behavioral

Intervention Name(s)

calorie-restricted diet

Intervention Description

All subjects after randomization will be reviewed and evaluated by a nutritionist, and then will receive diet guidance. The clinical nutritionist will develop a written nutrition plan for each subject. The nutrition plan of this study adopted the method of calorie restriction diet (CRD) to develop a diet, which required 83.68 kJ/kg of energy per day, 1.2 g/kg of protein per day, 40%~55% of carbohydrate energy supply ratio, and 20%~30% of fat energy supply ratio, to ensure the intake of vegetables, fruits and other rich dietary fiber, and drinking more than 1.5 L per day. The nutritionist will explain the method of food exchange in detail to enrich the food types of patients. The diet diary will be distributed to each subject, and the subjects will be required to make a return visit once every four weeks, return the diet diary each time, and receive guidance according to their compliance.

Intervention Type

Behavioral

Intervention Name(s)

physical exercise

Intervention Description

All subjects after randomization will be reviewed and evaluated by a trainer, and then will receive guidance of physical exercise.The trainer will formulate an exercise plan for each subject. The exercise plan consists of 30 minutes of moderate and low intensity continuous aerobic exercise every day, with a frequency of 5-7 days/week. The form of exercise can be determined according to personal hobbies, such as fast walking, jogging, climbing, swimming, etc. The exercise diary will be distributed to each subject, and the subjects are required to make a return visit once every four weeks, return the exercise diary each time, and the trainer will provide guidance to the subjects according to their compliance.

Primary Outcome Measure Information:

Title

Percentage change in bodyweight at 12 weeks for semaglutide versus metformin

Description

Difference between body weight at 12 weeks and baseline divided by baseline body weight

Time Frame

at the end of 12 weeks of treatment

Title

Achievement of weight reduction of at least 5% at 12 weeks for semaglutide versus metformin

Description

Proportion of patients with weight loss at least 5% at 12 weeks of treatment

Time Frame

at the end of 12 weeks of treatment

Secondary Outcome Measure Information:

Title

HOMA-IR at 12 weeks of treatment

Description

compare HOMA-IR at 12 weeks of treatment among three groups

Time Frame

at the end of 12 weeks of treatment

Title

testosterone level at 12 weeks of treatment

Description

compare testosterone level at 12 weeks of treatment among three groups

Time Frame

at the end of 12 weeks of treatment

Title

androstenedione level at 12 weeks of treatment

Description

compare androstenedione level at 12 weeks of treatment among three groups

Time Frame

at the end of 12 weeks of treatment

Title

FAI (Free Androgen Index) at 12 weeks of treatment

Description

compare FAI at 12 weeks of treatment among three groups

Time Frame

at the end of 12 weeks of treatment

Other Pre-specified Outcome Measures:

Title

Depression score by self-rating depression scale (SDS）at 12 weeks of treatment

Description

Zung self-rating depression scale (SDS) contains 20 items. Each item is divided into four grades according to the frequency of symptoms, of which 10 are positive and 10 are negative. Positive scoring question rated as 1, 2, 3 and 4 in turn and reverse scoring questions rated as 4, 3, 2 and 1. Add all the scores to get the total rough score, and then multiply the rough score by 1.25 to get the integral part as the standard score. The lower the score, the better. According to the criteria of Chinese population, the cut-off value of SDS standard score is 53 points, of which 53-62 points is mild depression, 63-72 points is moderate depression, and more than 73 points is severe depression. SDS standard score ≥ 50 indicates depressive symptoms. Depression severity is evaluated by cumulative score of each item/80. Those below 0.5 are not depressed; 0.5-0.59 is mild depression; 0.6-0.69 is moderate to severe; more than 0.7 is severe depression.

Time Frame

at the end of 12 weeks of treatment

Title

Anxiety score by self-rating anxiety scale (SAS）at 12 weeks of treatment

Description

Zung self-reating anxiety scale (SAS) adopts a four-grade score, which is mainly used to assess the frequency of symptoms. The standard is: "1" means no or little time; "2" means sometimes; "3" means most of the time; "4" means most or all of the time. Of the 20 items, 15 items are stated in negative words, and scored in the order of 1-4 above. The remaining five items are stated in positive words and scored in reverse order of 4 to 1. The main statistical indicator of SAS is the total score. Add the scores of 20 items to get a rough score. Multiply the rough score by 1.25 and take the integer part to get the standard score. According to the criteria of Chinese population, the cut-off value of SAS standard score is 50 points, of which 50-59 points is mild anxiety, 60-69 points is moderate anxiety, and more than 70 points is severe anxiety.

Time Frame

at the end of 12 weeks of treatment

Title

Diet score by TFEQ-18 (three factor eating questionaire) at 12 weeks of treatment

Description

The Three-Factor Eating Questionnaire Revised 18-item includes three dimensions of questions: non-controlled eating (9 items), cognitive restricted eating (6 items), and emotional eating (3 items). Uncontrolled eating refers to a tendency to lose control of excessive eating when feeling hungry or stimulated by external factors. Cognitive restriction refers to consciously limiting food intake to control weight or promote weight loss. Emotional eating refers to the tendency to overeat under some negative emotional conditions. Questions 1 to 18 are scored with 1 to 4 points. The total score of the three dimensions is the total score of the scale. The higher the score of each dimension of the questionnaire, the higher the tendency of uncontrolled eating, cognitive restriction of eating and emotional eating.

Time Frame

at the end of 12 weeks of treatment

Title

Quality of life score at 12 weeks of treatment

Description

The World Health Organization Quality of Life (WHOQOL) - BREF can generate scores in four fields. The scale contains two independent analysis items: Q1 asks the individual's total subjective feelings about their own quality of life, and Q2 asks the individual's total subjective feelings about their own health status. The domain score is positive (that is, the higher the score, the better the quality of life). The domain score is obtained by calculating the average score of the items to which it belongs and multiplying by 4.

Time Frame

at the end of 12 weeks of treatment

Title

Ovulation rate at 24 weeks of follow-up after the end of treatment

Description

Number of patients with ovulation after natural and ovulation induction treatment/total number of patients

Time Frame

at the end of 24 weeks of follow-up after the end of treatment

Title

Clinical pregnancy rate at 24 weeks of follow-up after the end of treatment

Description

Clinical pregnancy rate=clinical pregnancy cycles/transplantation cycles

Time Frame

at the end of 24 weeks of follow-up after the end of treatment

Title

Cumulative pregnancy rate at 24 weeks of follow-up after the end of treatment

Description

Cumulative pregnancy rate=number of all pregnant patients/total number of patients

Time Frame

at the end of 24 weeks of follow-up after the end of treatment

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

22 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tingting Zhang, M.D.

Phone

86-10-83575103

cathine@sina.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tingting Zhang, M.D.

Organizational Affiliation

Peking University First Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

PekingUFH

City

Peking

State/Province

Beijing

ZIP/Postal Code

100034

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24362411

Citation

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Semaglutide Improves Metabolic Abnormalities and Fertility in Obese Infertile Women With Polycystic Ovary Syndrome

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