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CRD vs. Met in Patients With Obese PCOS Infertility

Primary Purpose

Polycystic Ovary Syndrome

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
CRD
Metformin
Sponsored by
Shanghai First Maternity and Infant Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovary Syndrome

Eligibility Criteria

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

Inclusion Criteria: a diagnosis of polycystic ovary syndrome (PCOS) based on the Rotterdam diagnostic criteria; age 20-35 years old; a body-mass index over 23; have requirements for fertility. Exclusion Criteria: acute or chronic viral hepatitis; serious liver dysfunction or chronic kidney disease; serious cardiovascular or cerebrovascular disease; patients with a history of acute/chronic infection, severe cardiovascular and cerebrovascular diseases, and malignant tumors; have drugs for PCOS such as glucocorticoids and anti-androgen drugs (spironolactone, cyproterone acetate, flutamide, etc.) within 3 months; congenital or secondary uterine abnormalities; use of medications that affect weight or energy balance such as Metformin within 3 months; undergoing weight loss treatment (weight change greater than 5% in the past 3 months) or have a history of gastrointestinal surgery; tubal obstruction; the total number of motile sperm of male partner is less than 10 million; any other situations that might affect the trial.

Sites / Locations

  • Shanghai First Maternity and Infant HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CRD group

Control group

Arm Description

Patients in the calorie-restricted diet (CRD) group will have strict calorie-restriction diets for 8 weeks and then weight stability for 4 weeks.

Patients in the control group will receive regular diets and metformin 1500 mg daily for 12 weeks. Participants allocated to the control group are followed by the conventional approach (usual care) based on regular visits respecting the usual schedule dictated by the rules of general practice.

Outcomes

Primary Outcome Measures

Live birth during the period of ovulation induction
Live birth will be defined as the delivery of one or more living infants (≥22 week's gestation or birth weight more than 500g). The outcome could be assessed by clinical data and clinical diagnosis.

Secondary Outcome Measures

Fasting blood glucose (FBG)
A laboratory test that determines the level of glucose in the blood after an overnight fast, used especially to diagnose diabetes and prediabetes. The normal interval is 3.9-6.1mmol/L. The outcome could be assessed by clinical data and clinical test.
Fasting insulin (FINS)
The level of insulin in the blood during fasting (usually in the morning when fasting). The normal interval is 5~20 μIU. The outcome could be assessed by clinical data and clinical test.
Oral glucose tolerance test (OGTT)
An oral glucose tolerance test (OGTT) is a diagnostic tool used to evaluate how an individual's body metabolizes sugar. Often used to diagnose diabetic conditions, an oral glucose tolerance test requires minimal preparatory measures and may be safely administered during pregnancy. The outcome could be assessed by clinical data and clinical test.
Insulin release test (IRT)
Quantitative oral glucose during fasting increases blood glucose and stimulates pancreatic β cells to release insulin. By measuring plasma insulin levels during fasting and 0.5h, 1h, 2h, and 3h after taking sugar, we can understand the secretion and reserve function of pancreatic β cells, which is also helpful for the classification of diabetes mellitus and guide treatment. The outcome could be assessed by clinical data and clinical test.
Blood lipid
Lipid related indicators include cholesterol, triglycerides. The outcome could be assessed by clinical data and clinical test.
Kidney function index
Blood tests that are included in the kidney function test include measuring for creatinine and blood urea nitrogen (BUN). The outcome could be assessed by clinical data and clinical test.
Liver function index
Liver function index includes alanine aminotransferase (ALT), alkaline phosphatase (ALP) . The outcome could be assessed by clinical data and clinical test.
Free testosterone (FT)
The average serum testosterone concentration is 0.43ng/ml, the high limit is 0.68ng/ml, if more than 0.7ng/m1 (equal to 2.44nmol/L), it is called hypertestosterone, or hyperandrogenemia. The outcome could be assessed by clinical data and clinical test.
Total testosterone (TT)
The normal range of female testosterone is 0.1-0.75ng /ml, testosterone is the main sex hormone of the human body, men and women have secretion, male testosterone secretion is 20-30 times the amount of female testosterone secretion, it is very important to maintain the second sexual characteristics, bone and muscle strength. The outcome could be assessed by clinical data and clinical test.
Sex Hormone Binding Globulin (SHBG)
A globulin synthesized by liver cells that can bind sex hormones, also known as testosterone - estrogen binding globulin or steroidal binding protein, is an important carrier of sex hormones, which can have an important impact on the regulation of sex hormone levels and bioavailability in the body. Clinical detection of SHBG level can provide scientific reference value for disease detection and judgment. The normal interval is 20-130nmol/L for women. The outcome could be assessed by clinical data and clinical test.
Liver transient elastography(TE)
TE may be used to monitor disease progression or regression via serial measurements and to guide further management including treatment. The outcome could be assessed by clinical data and clinical test.
Weight
Unit: kilogram (kg). The outcome could be assessed by clinical data and clinical test.
Height
Unit: meter (m). The outcome could be assessed by clinical data and clinical test.
Body Mass Index (BMI)
BMI = weight (in kg)/ height^2 (in m^2).
Waist circumference
Unit: centimeter (cm). The outcome could be assessed by clinical data and clinical test.
Body fat
Body fat is measured by body fat scale. The outcome could be assessed by clinical data and clinical test.
Lean body weight
Lean body weight refers to the total weight of organs, bones, and muscles. The outcome could be assessed by clinical data and clinical test.
Blood pressure (BP)
Blood pressure is a measurement of the force of blood against the arterial walls when the heart pumps. The pressure is measured in millimeters of mercury (mmHg) and is expressed as two numbers. For example, the optimal BP for an adult is 120 over 80, or 120/80. A pressure reading of 120 over 80 or lower is considered healthy. If the systolic number ranges above 120 to 139 or the diastolic number ranges above 80 to 89, a person is considered to have pre-hypertension. Systolic readings from 140 to 159 or diastolic readings from 90 to 99 are classified as stage 1 hypertension. Systolic measurements of 160 or above or diastolic measurements of 100 or above indicate the severe condition of stage 2 hypertension. The outcome could be assessed by clinical data and clinical test.
Hospital Anxiety and Depression Scale (HADS)
The purpose of the HADS was to screen for clinically significant anxiety and depressive symptoms in medically ill patients. Content The HADS-A includes specific items that assess generalized anxiety including tension, worry, fear, panic, difficulties in relaxing, and restlessness. The total score for the HADS-A can range from 0 to 21. The following guidelines are recommended for the interpretation of scores: 0-7 for normal or no anxiety, 8-10 for mild anxiety, 11-14 for moderate anxiety, and 12-21 for severe anxiety.
Biochemical pregnancy
A pregnancy diagnosed only by the detection of beta hCG in serum or urine. The outcome could be assessed by clinical data and clinical diagnosis.
Ectopic pregnancy
Ectopic pregnancy (EP) is defined as the implantation and development of a fertilized ovum anywhere outside of the uterine cavity. The outcome could be assessed by clinical data and clinical diagnosis.
Pregnancy failure
Pregnancy failure, otherwise termed as pregnancy loss or miscarriage, can occur at different stages during this process and many different pathophysiological mechanisms may be implicated. The outcome could be assessed by clinical data and clinical diagnosis.
Birth weight
Macrosomia is defined in a newborn as a birth weight more than two standard deviations above the mean percentile for gestational age, >90th percentile weight for gestational age, or a birth weight greater than 4000g at term. The outcome could be assessed by clinical data and clinical diagnosis.
Neonatal complications
Neonatal complications include intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome, bronchopulmonary dysplasia, jaundice. The outcome could be assessed by clinical data and clinical diagnosis.

Full Information

First Posted
August 31, 2023
Last Updated
September 14, 2023
Sponsor
Shanghai First Maternity and Infant Hospital
Collaborators
RenJi Hospital, Shanghai 10th People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06049186
Brief Title
CRD vs. Met in Patients With Obese PCOS Infertility
Official Title
Comparison of Live Birth Rates Between Calorie-restricted Diets and Metformin Interventions Prior to Ovulation Induction Therapy in Patients With Overweight/Obese Polycystic Ovary Syndrome Combined With Infertility
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 15, 2023 (Anticipated)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai First Maternity and Infant Hospital
Collaborators
RenJi Hospital, Shanghai 10th People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease and a major cause of anovulatory infertility in reproductive-aged women. From 2010 to 2020, it was found that the prevalence of PCOS in reproductive-aged women in China reached 7.8%, an increase of 65% over 10 years ago. Many of them are overweight or obese. Weight loss including diet modifications can significantly reduce reproductive and metabolic disorders of PCOS and is recommended as a first step in the treatment of overweight or obese women with PCOS. Many weight loss programs have been proposed, including calorie-restriction diet (CRD) intervention. Whether CRD intervention prior to ovulation induction therapy could improve live birth rates in overweight/obese PCOS women has not been illustrated.
Detailed Description
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease and a major cause of anovulatory infertility in reproductive-aged women. Rotterdam criteria state the definition of PCOS is that women must present with two of the following three signs/symptoms-hyperandrogenism, chronic anovulation/oligomenorrhea, and polycystic ovaries-in the absence of other diseases that promote these symptoms. From 2010 to 2020, it was found that the prevalence of PCOS in reproductive-aged women in China reached 7.8%, an increase of 65% over 10 years ago. Many of them are overweight or obese. Weight loss including diet modifications can significantly reduce reproductive and metabolic disorders of PCOS and is recommended as a first step in the treatment of overweight or obese women with PCOS. Many weight loss programs have been proposed, including calorie-restriction diet (CRD) intervention. Whether CRD intervention prior to ovulation induction therapy could improve live birth rates in overweight/obese PCOS women has not been illustrated. This research is aimed to evaluate whether CRD intervention prior to ovulation induction could promote reproductive health in overweight or obese PCOS women with fertility requirements and provide an evidence-based nutrition advice for clinical practice.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Comparison of live birth rates between calorie-restricted diets and metformin interventions prior to ovulation induction therapy in patients with overweight/obese polycystic ovary syndrome combined with Infertility.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
406 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CRD group
Arm Type
Experimental
Arm Description
Patients in the calorie-restricted diet (CRD) group will have strict calorie-restriction diets for 8 weeks and then weight stability for 4 weeks.
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
Patients in the control group will receive regular diets and metformin 1500 mg daily for 12 weeks. Participants allocated to the control group are followed by the conventional approach (usual care) based on regular visits respecting the usual schedule dictated by the rules of general practice.
Intervention Type
Behavioral
Intervention Name(s)
CRD
Other Intervention Name(s)
Calorie-restricted diet
Intervention Description
During the initial 8 weeks of the trial, polycystic ovary syndrome (PCOS) patients are instructed to follow a diet of 1200 to 1500 kcal per day supervised by dietitians. The CRD includes a combination of 40 to 55% of calories from carbohydrates, 15 to 20% from protein, and 20 to 30% from fat; this regimen represented approximately 75% of the participants' daily caloric intake at baseline. All the participants receive dietary counseling daily during the trial.
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Metformin treatment
Intervention Description
After randomization, patients entering the metformin group will be given 1500 mg daily (bid/tid) metformin and regular diets as control. Participants allocated to the control group are followed by the conventional approach (usual care) based on regular visits respecting the usual schedule dictated by the rules of general practice.
Primary Outcome Measure Information:
Title
Live birth during the period of ovulation induction
Description
Live birth will be defined as the delivery of one or more living infants (≥22 week's gestation or birth weight more than 500g). The outcome could be assessed by clinical data and clinical diagnosis.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Fasting blood glucose (FBG)
Description
A laboratory test that determines the level of glucose in the blood after an overnight fast, used especially to diagnose diabetes and prediabetes. The normal interval is 3.9-6.1mmol/L. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Fasting insulin (FINS)
Description
The level of insulin in the blood during fasting (usually in the morning when fasting). The normal interval is 5~20 μIU. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Oral glucose tolerance test (OGTT)
Description
An oral glucose tolerance test (OGTT) is a diagnostic tool used to evaluate how an individual's body metabolizes sugar. Often used to diagnose diabetic conditions, an oral glucose tolerance test requires minimal preparatory measures and may be safely administered during pregnancy. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Insulin release test (IRT)
Description
Quantitative oral glucose during fasting increases blood glucose and stimulates pancreatic β cells to release insulin. By measuring plasma insulin levels during fasting and 0.5h, 1h, 2h, and 3h after taking sugar, we can understand the secretion and reserve function of pancreatic β cells, which is also helpful for the classification of diabetes mellitus and guide treatment. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Blood lipid
Description
Lipid related indicators include cholesterol, triglycerides. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Kidney function index
Description
Blood tests that are included in the kidney function test include measuring for creatinine and blood urea nitrogen (BUN). The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Liver function index
Description
Liver function index includes alanine aminotransferase (ALT), alkaline phosphatase (ALP) . The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Free testosterone (FT)
Description
The average serum testosterone concentration is 0.43ng/ml, the high limit is 0.68ng/ml, if more than 0.7ng/m1 (equal to 2.44nmol/L), it is called hypertestosterone, or hyperandrogenemia. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Total testosterone (TT)
Description
The normal range of female testosterone is 0.1-0.75ng /ml, testosterone is the main sex hormone of the human body, men and women have secretion, male testosterone secretion is 20-30 times the amount of female testosterone secretion, it is very important to maintain the second sexual characteristics, bone and muscle strength. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Sex Hormone Binding Globulin (SHBG)
Description
A globulin synthesized by liver cells that can bind sex hormones, also known as testosterone - estrogen binding globulin or steroidal binding protein, is an important carrier of sex hormones, which can have an important impact on the regulation of sex hormone levels and bioavailability in the body. Clinical detection of SHBG level can provide scientific reference value for disease detection and judgment. The normal interval is 20-130nmol/L for women. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Liver transient elastography(TE)
Description
TE may be used to monitor disease progression or regression via serial measurements and to guide further management including treatment. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Weight
Description
Unit: kilogram (kg). The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Height
Description
Unit: meter (m). The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Body Mass Index (BMI)
Description
BMI = weight (in kg)/ height^2 (in m^2).
Time Frame
Baseline period and 3 months
Title
Waist circumference
Description
Unit: centimeter (cm). The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Body fat
Description
Body fat is measured by body fat scale. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Lean body weight
Description
Lean body weight refers to the total weight of organs, bones, and muscles. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Blood pressure (BP)
Description
Blood pressure is a measurement of the force of blood against the arterial walls when the heart pumps. The pressure is measured in millimeters of mercury (mmHg) and is expressed as two numbers. For example, the optimal BP for an adult is 120 over 80, or 120/80. A pressure reading of 120 over 80 or lower is considered healthy. If the systolic number ranges above 120 to 139 or the diastolic number ranges above 80 to 89, a person is considered to have pre-hypertension. Systolic readings from 140 to 159 or diastolic readings from 90 to 99 are classified as stage 1 hypertension. Systolic measurements of 160 or above or diastolic measurements of 100 or above indicate the severe condition of stage 2 hypertension. The outcome could be assessed by clinical data and clinical test.
Time Frame
Baseline period and 3 months
Title
Hospital Anxiety and Depression Scale (HADS)
Description
The purpose of the HADS was to screen for clinically significant anxiety and depressive symptoms in medically ill patients. Content The HADS-A includes specific items that assess generalized anxiety including tension, worry, fear, panic, difficulties in relaxing, and restlessness. The total score for the HADS-A can range from 0 to 21. The following guidelines are recommended for the interpretation of scores: 0-7 for normal or no anxiety, 8-10 for mild anxiety, 11-14 for moderate anxiety, and 12-21 for severe anxiety.
Time Frame
Baseline period and 3 months
Title
Biochemical pregnancy
Description
A pregnancy diagnosed only by the detection of beta hCG in serum or urine. The outcome could be assessed by clinical data and clinical diagnosis.
Time Frame
8 months
Title
Ectopic pregnancy
Description
Ectopic pregnancy (EP) is defined as the implantation and development of a fertilized ovum anywhere outside of the uterine cavity. The outcome could be assessed by clinical data and clinical diagnosis.
Time Frame
8 months
Title
Pregnancy failure
Description
Pregnancy failure, otherwise termed as pregnancy loss or miscarriage, can occur at different stages during this process and many different pathophysiological mechanisms may be implicated. The outcome could be assessed by clinical data and clinical diagnosis.
Time Frame
8 months
Title
Birth weight
Description
Macrosomia is defined in a newborn as a birth weight more than two standard deviations above the mean percentile for gestational age, >90th percentile weight for gestational age, or a birth weight greater than 4000g at term. The outcome could be assessed by clinical data and clinical diagnosis.
Time Frame
18 months
Title
Neonatal complications
Description
Neonatal complications include intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome, bronchopulmonary dysplasia, jaundice. The outcome could be assessed by clinical data and clinical diagnosis.
Time Frame
18 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: a diagnosis of polycystic ovary syndrome (PCOS) based on the Rotterdam diagnostic criteria; age 20-35 years old; a body-mass index over 23; have requirements for fertility. Exclusion Criteria: acute or chronic viral hepatitis; serious liver dysfunction or chronic kidney disease; serious cardiovascular or cerebrovascular disease; patients with a history of acute/chronic infection, severe cardiovascular and cerebrovascular diseases, and malignant tumors; have drugs for PCOS such as glucocorticoids and anti-androgen drugs (spironolactone, cyproterone acetate, flutamide, etc.) within 3 months; congenital or secondary uterine abnormalities; use of medications that affect weight or energy balance such as Metformin within 3 months; undergoing weight loss treatment (weight change greater than 5% in the past 3 months) or have a history of gastrointestinal surgery; tubal obstruction; the total number of motile sperm of male partner is less than 10 million; any other situations that might affect the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Miaoxin Chen, Dr
Phone
20261000
Email
chenmiaoxin@51mch.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miaoxin Chen, Dr
Organizational Affiliation
Shanghai First Maternity and Infant Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Shanghai First Maternity and Infant Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201204
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miao Chen, Dr
Phone
20261000
Email
chenmiaoxin@51mch.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35669932
Citation
Yang R, Li Q, Zhou Z, Qian W, Zhang J, Wu Z, Jin L, Wu X, Zhang C, Zheng B, Tan J, Hao G, Li S, Tian T, Hao Y, Zheng D, Wang Y, Norman RJ, Li R, Liu P, Qiao J. Changes in the prevalence of polycystic ovary syndrome in China over the past decade. Lancet Reg Health West Pac. 2022 May 31;25:100494. doi: 10.1016/j.lanwpc.2022.100494. eCollection 2022 Aug.
Results Reference
background
PubMed Identifier
32814159
Citation
Lie Fong S, Douma A, Verhaeghe J. Implementing the international evidence-based guideline of assessment and management of polycystic ovary syndrome (PCOS): how to achieve weight loss in overweight and obese women with PCOS? J Gynecol Obstet Hum Reprod. 2021 Jun;50(6):101894. doi: 10.1016/j.jogoh.2020.101894. Epub 2020 Aug 16.
Results Reference
background
PubMed Identifier
35199348
Citation
Shahid R, Iahtisham-Ul-Haq, Mahnoor, Awan KA, Iqbal MJ, Munir H, Saeed I. Diet and lifestyle modifications for effective management of polycystic ovarian syndrome (PCOS). J Food Biochem. 2022 Jul;46(7):e14117. doi: 10.1111/jfbc.14117. Epub 2022 Feb 24.
Results Reference
background
PubMed Identifier
34371961
Citation
Szczuko M, Kikut J, Szczuko U, Szydlowska I, Nawrocka-Rutkowska J, Zietek M, Verbanac D, Saso L. Nutrition Strategy and Life Style in Polycystic Ovary Syndrome-Narrative Review. Nutrients. 2021 Jul 18;13(7):2452. doi: 10.3390/nu13072452.
Results Reference
background
PubMed Identifier
32103756
Citation
Paoli A, Mancin L, Giacona MC, Bianco A, Caprio M. Effects of a ketogenic diet in overweight women with polycystic ovary syndrome. J Transl Med. 2020 Feb 27;18(1):104. doi: 10.1186/s12967-020-02277-0.
Results Reference
background

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CRD vs. Met in Patients With Obese PCOS Infertility

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