Low-Carb Versus Mediterranean Diet in PCOS

Study Overview
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Brief Summary
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This is a randomized controlled trial of two diets (low-carbohydrate and Mediterranean diet) in the treatment of women with polycystic ovary syndrome (PCOS). The trial assesses the effects of the two diets on clinical, metabolic and hormonal parameters, inflammatory markers and gut microbiota . This study is an interventional, randomized controlled trial, open-labeled.

Detailed Description
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The study aims to clarify the impact of nutritional recommendations for women with polycystic ovary syndrome on clinical, metabolic and hormonal parameters, inflammatory markers and gut microbiota . Women with PCOS are randomized into 2 treatment groups: one group on a low-carbohydrate diet and the other on a Mediterranean diet. The adhearance to a prescribed diet will be controlled through food intake diaries using a mobile application with electronic reporting forms.

Official Title
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Low-Carbohydrate Diet Versus Mediterranean Diet as Treatment for Women With Polycystic Ovary Syndrome.

Conditions
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Polycystic Ovary Syndrome (PCOS)

Intervention / Treatment
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* Other: low-carbohydrate diet
* Other: Mediterranean diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with PCOS between the ages of 18-40 years and with a body mass index of less than or equal to 45. Fulfillment of at least two of the following three criteria for PCOS, adopted by the Rotterdam Consensus in 2003 (Rotterdam ESHRE / ASRM-Sponsored PCOS Consensus Workshop Group): signs of hyperandrogenemia - clinical and / or biochemical (increase in the index of free androgens or total testosterone) signs of chronic anovulation ultrasound signs: the number of follicles in the ovary ≥ 20 and / or ovarian volume ≥ 10 ml in any ovary in the case of gynecological age 8 or more years after menarche. Exclusion Criteria: The presence of hyperprolactinemia Cushing's syndrome Ongenital hyperplasia of the adrenal cortex Hypothyroidism Androgen-producing tumors Regular use of drugs and dietary supplements that affect the function of the ovaries Adrenal glands Metabolism of carbohydrates Lipids Microbiota composition during the 2 months preceding the study Pregnancy Lactation Significant comorbidities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-carbohydrate diet<br>subjects in this arm are given detailed instructions and coaching in following a low-carbohydrate diet. | Other: low-carbohydrate diet<br>* subjects in this arm are given detailed instructions and coaching in following a low-carbohydrate diet.<br>|
| Experimental: Mediterranean diet<br>subjects in this arm are given detailed instructions and coaching in following a Mediterranean diet. | Other: Mediterranean diet<br>* subjects in this arm are given detailed instructions and coaching in following a Mediterranean diet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index | Changes in HOMA-IR index (fasting insulin [mU/l] * fasting glucose [mmol/L]/22.5) after intervention | 12 weeks | 
| 2. Free androgen index | Changes in free androgen index [ (total testosterone level / sex hormone binding globulin (SHBG) level) * 100]. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Total testosterone | Changes in total testosterone levels [nmol/L] in serum after intervention | 12 weeks | 
| 2. Androstenedione | Changes in androstenedione levels in serum after intervention [ng/ml] | 12 weeks | 
| 3. Anti-Müllerian hormone (AMH) | Changes in AMH levels in serum after intervention [ng/ml] | 12 weeks | 
| 4. 17-Hydroxyprogesterone (17-OH-progesterone) | Changes in 17-OH-progesterone levels in serum after intervention [ng/ml] | 12 weeks | 
| 5. Luteinizing hormone (LH) | Changes in LH levels in serum after intervention [mU/ml] | 12 weeks | 
| 6. Follicle-stimulating hormone (FSH) | Changes in FSH levels in serum after intervention [mU/ml] | 12 weeks | 
| 7. Insulin | Changes in insulin levels in serum as measured with a two-hour oral glucose tolerance test (75 mg glucose in 300 ml water, blood draws at 0 minutes, 60 min and 120 min) [mU/l] | 12 weeks | 
| 8. Glucose | Changes in glucose levels in plasma as measured with a two-hour oral glucose tolerance test (75 mg glucose in 300 ml water, blood draws at 0 minutes, 60 min and 120 min) [mmol/L] | 12 weeks | 
| 9. Matsuda index | Changes in matsuda index after intervention measured with the formula M=10000/squareroot(glucose0 * insulin0 * Mean OGTT glucose concentration * Mean OGTT insulin concentration) | 12 weeks | 
| 10. Hirsutism | measured by Ferriman-Gallwey-score (mFG-score), ranging from 0 to 36, with 0 being the best possible value and 36 the worst | 12 weeks | 
| 11. Body-mass-index (BMI) | BMI measured with the formula BMI=weight [kg]/height² [m] | 12 weeks | 
| 12. waist-to-hip ratio | Calculated with the formula: waist circumference/hip circumference | 12 weeks | 
| 13. Gut microbiome composition | Changes in gut microbiome composition measured from stool samples via 16S-RNA gene sequencing | 12 weeks | 
| 14. Inflammatory markers | Changes in inflammatory markers (Cytokines) measured by Human Cytokine/Chemokine/Growth Factor Panel A. 48 plex kit, pg/mL | 12 weeks | 
| 15. Untargeted metabolomics | Serum samples will be analysed to identify biomarkers differentially changing in response to the studied diets using ultra-high performance liquid chromatography (UHPLC). | 12 weeks | 
| 16. Untargeted metabolomics | Serum samples will be analysed to identify biomarkers differentially changing in response to the studied diets using ultra-high performance mass spectrometry (MS). | 12 weeks | 
| 17. Serum Low-density lipoproteins (LDL) | Changes in serum Low-density lipoproteins (LDL), mmol/L | 12 weeks | 
| 18. Serum high-density lipoproteins (LDL) | Changes in serum high-density lipoproteins (LDL), mmol/L | 12 weeks | 
| 19. Serum triglyceride levels, mmol/L | Changes in serum triglyceride levels, mmol/L | 12 weeks | 
| 20. Ovulation rate | Percent of women with ovulation recorded by serial transvaginal ultrasound after 8 weeks of participating in the study | 12 weeks | 
| 21. Ovarian volume | Changes in ovarian volume (cm3) measured by transvaginal ultrasound in early follicular phase or after 3 months of amenorrhea | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiome, obesity, Mediterranean diet, low-carb diet