Clinical trial NCT06545721: Weight Cycling on Hyperandrogenemia and Insulin Resistance in Polycystic Ovary Syndrome
Official title: The Effect and Mechanism Of Weight Cycling on Hyperandrogenemia And Insulin Resistance in Polycystic Ovary Syndrome
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Polycystic Ovary Syndrome
Keywords: Weight Cycling
Hyperandrogenemia
Insulin Resistance
High-protein diet
Transcriptome
Metabolome
Inflammatory status
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2024-08-09
Enrollment: 425
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: the sample size for the normal weight group is 45, and the sample size for the overweight/obese group is 380.
Primary purpose: OTHER

Brief summary: This study prospectively includes PCOS patients with normal weight and overweight/obesity, closely follows up and intensively manages them, and observes the level and distribution of weight reduction achieved by patients after lifestyle intervention (high-protein diet for weight loss). Additionally, it aims to provide reference for setting weight loss targets for future PCOS patients by comparing the differences in clinical improvement among patients achieving different degrees of weight reduction (\<2% \[equivalent to no weight loss\], 2-5%, 5-10%, ≥10%) at different time points (3 months, 6 months) following dietary intervention. Furthermore, this study will compare the differences in reproductive and metabolic marker improvements between baseline PCOS patients experiencing weight rebound, those who successfully lost weight, and those who experienced weight rebound. This will help explore the impact of weight cycling on PCOS-related manifestations. Finally, at a genetic level, the study will analyze potential mechanisms underlying different outcome indicators by comparing differences in metagenomics, transcriptomics, and metabolomics among patient groups.

Detailed description: This study is a single-center, prospective cohort study that enrolled PCOS patients after screening. The patients were categorized into two groups based on their BMI: a normal weight group (18.5 kg/m2 ≤ BMI \< 24 kg/m2) with a sample size of 45 and an overweight/obese group (BMI ≥ 24 kg/m2) with a sample size of 380, totaling 425 cases.

For the normal weight PCOS patients, interventions included control of total energy intake, adjustment of dietary structure, exercise, and behavioral intervention to prevent weight gain over a follow-up period of three months. If weight gain occurred during the follow-up period, these patients were transferred to the overweight/obese group for intensified intervention.

The overweight/obese PCOS patients received intensive intervention in accordance with high-protein diet adaptation criteria. This involved high-protein diets combined with exercise and behavioral intervention for weight reduction. After three months of follow-up, if they achieved their weight-loss goal, they transitioned to a low-energy diet and exercise intervention program to maintain their weight. If the goal was not met after three months, they continued with the high-protein weight-loss program.

The study compared differences in improvement in indicators such as insulin resistance (IR), blood androgen levels, inflammatory factors among different degrees of weight loss (\<2%, 2% ≤weight loss \<5%, 5%≤weight loss\<10%, ≥10%), analyzing potential mechanisms.

For individuals experiencing weight cycling, differences in IR levels before and after rebounding from body mass were compared alongside changes in androgen levels and other metabolic indicators. This aimed to explore the impact of body mass cycling on clinical indicators while analyzing potential causes.

Eligibility criteria: Inclusion Criteria:

1. Women aged 18-45 years in the reproductive period;
2. Women who have previously met the Rotterdam diagnostic criteria (at least 2 of the following 3 criteria have been confirmed, and have been diagnosed with PCOS): 1) Oligomenorrhea and/or anovulation; 2) clinical and/or biochemical evidence of hyperandrogenism; 3) ultrasound showing the presence of unilateral or bilateral polycystic ovaries;
3. Inclusion of 50 women in the normal weight group: 18.5 kg/m² ≤ BMI \< 24 kg/m²; Inclusion of 400 women in the overweight/obese group: BMI ≥ 24 kg/m²;
4. Voluntarily participate in the intervention and sign an informed consent form.

Exclusion Criteria:

1. Currently pregnant or lactating, or have had a recent (within 6 months) plan for pregnancy;
2. Currently using known prescription weight loss medications (such as GLP-1RA, orlistat, topiramate, etc.);
3. History of weight loss surgery;
4. History of severe cardiovascular or cerebrovascular diseases; severe liver or kidney dysfunction (ALT \> 3 times the upper limit of normal, or creatinine \> 1.5 times the upper limit of normal); chronic or active gastrointestinal inflammatory diseases; severe systemic diseases; active malignant tumors;
5. Secondary obesity: including hypothalamic or pituitary obesity, obesity secondary to glucocorticoid use, hypogonadism-induced obesity, etc.;
6. Known history of serious endocrine system diseases;
7. Poor compliance with planned dietary interventions (psychiatric disorders such as binge eating disorder, anorexia nervosa, severe anxiety/depression);
8. Unable to follow up on time or deemed non-cooperative by the investigator.

Primary outcomes:
measure: Weight loss rate
timeFrame: 6 month
measure: Levels of insulin resistance
timeFrame: 6 month
Secondary outcomes:
measure: Fasting insulin level（FINS）
timeFrame: 6 month
measure: Fasting blood sugar（FBG）
timeFrame: 6 month
measure: Blood levels of androgen hormones (total testosterone, free testosterone index)
timeFrame: 6 month
measure: Blood lipid levels (LDL-C, HDL-C, total cholesterol)
timeFrame: 6 month
measure: Levels of inflammatory factors (CRP, IL-6, TAC, GSH)
timeFrame: 6 month
measure: BMI
timeFrame: 6 month
measure: Waist
timeFrame: 6 month
measure: waist-to-hip ratio
timeFrame: 6 month
measure: Body fat percentage and distribution
timeFrame: 6 month
measure: Weight rebound rate
timeFrame: 6 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Wei Chen, PhD
role: PRINCIPAL_INVESTIGATOR
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