Ketogenic Diet in PCOS With Obesity and Insulin Resistance

Study Overview
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Brief Summary
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The purpose of the VLCKD randomized clinical trial is to demonstrate the superiority of very low calorie ketogenic diet with respect to the standard low calorie diet in reducing body weight and insulin resistance in obese and insulin resistant patients with Polycystic Ovary Syndrome

Detailed Description
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Consecutive patients coming to the Endocrinology and Diabetes Clinic of the S.Orsola hospital in Bologna with the suspicion of PCOS, during the study period, will be eligible to participate. In the screening phase, patients from the clinic conforming to the inclusion criteria will be invited to participate in the anovulation screening phase, lasting up to 8 weeks, during which measurements of LH, FSH, estradiol, progesterone and a gynecologic ultrasound will be done on 7th, 14th, 21st and 28th day of the presumed ovulatory cycle, or at any time if amenorrhea present. Consenting participants will provide written informed consent. Following the anovulation screening, the patients will be randomized in two arms of the study: 1. very low calorie ketogenic diet (VLCKD) and the 2. low calorie standard diet (LCD). The study is open label; thus, patients and investigators will not be blinded to treatment allocation due to the nature of the study intervention. The group assigned to the VLCKD will follow the VLCKD for 8 weeks, after which they will follow the LCD for the next 8 weeks. The group assigned to the LCD will follow the LCD for the entire length of the study (16 weeks.) At the start of the study, after 8 weeks and after 16 weeks, following measurements and tests will be done: clinical examination with the measurement of height, body mass, circumference at the waist and hip level, arterial systolic and diastolic pressure, heart rate, Ferriman-Gallwey and videodermoscopic evaluation of hirsutism and bioimpedance body composition measurement; blood will be taken for: lipid profile, hepatic transaminases, fasting glucose, fasting insulin, HbA1c, potassium, sodium, urea, calcium, phosphorus, total proteins, albumins, total bilirubin, uric acid, complete blood count, sex hormone binding globulin (SHBG), liquid chromatography-mass spectrometry measurement of testosterone, androstenedione, DHEA, 17OH-progesterone, 17OH-pregnenolone; dietary interview; psychological evaluation using the following questionnaires: Symptom Questionnaire, the Psychosocial index and the Psychological Well-Being scales.

Official Title
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Effect of Very Low Calorie Ketogenic Diet on Obese and Insulin-resistant Women With Polycystic Ovary Syndrome: a Controlled Randomized Trial

Conditions
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PCOS, Obesity, Insulin Resistance

Intervention / Treatment
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* Combination Product: Very low calorie ketogenic diet
* Behavioral: Low calorie standard diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PCOS according to the NIH criteria; Body mass index (BMI) between 30 and 35 kg/m3; HOMA index ≥ 3 (according to formula: (fasting glucose [mmol/L] × fasting insulin [mIU/L])/22.5) Written informed consent. Exclusion Criteria: Diabetes type 1 Exogenous insulin or insulin analogue therapy Obesity caused by endocrine disease other than PCOS Obesity caused by pharmacotherapy Use of a weight-loss diet in the past 3 months Use of contraceptive pills in the past 3 months Severe depression Other psychiatric diseases Alcohol or psychoactive substance abuse Severe hepatic insufficiency Renal calculosis Renal insufficiency Episodes of gout Malignant neoplasia Previous cardiovascular or cerebrovascular events Uncontrolled hypertension Water-electrolyte imbalance Any pharmacotherapy capable of interfering with glucose metabolism Any pharmacotherapy capable of interfering with steroid metabolism Menopause Pregnancy Lactation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Very low calorie ketogenic diet<br>Dietary intervention with a very low calorie ketogenic diet, using commercial products of the Pronokal PnK® method | Combination Product: Very low calorie ketogenic diet<br>* Dietary intervention with a very low calorie ketogenic diet, using commercial products of the Pronokal PnK® method<br>* Other names: Pronokal method;Behavioral: Low calorie standard diet<br>* Low calorie standard diet with no specified dietary supplement addition<br>|
| Active Comparator: Low calorie diet<br>Control treatment with a low calorie standard diet | Behavioral: Low calorie standard diet<br>* Low calorie standard diet with no specified dietary supplement addition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body mass index | Weight and height will be combined to report BMI in kg/m^2 | 16 weeks after the start of treatment | 
| Change in body composition measured by bioimpedentiometry | Fat mass and lean mass changes will be considered to estimate change in body composition and reported as % | 16 weeks after the start of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body mass index | Weight and height will be combined to report BMI in kg/m^2 | 8 weeks after the start of treatment | 
| Change in body composition measured by bioimpedentiometry | Fat mass and lean mass will be considered to estimate change in body composition and reported as % | 8 weeks after the start of the treatment | 
| Change in Homeostasis Model Assessment Index | Fasting glucose in mmol/L and fasting insulin in mcU/mL will be combined to report Homeostasis Model Assessment Index | 16 weeks after the start of the treatment | 
| Change in frequency of menstrual cycles | Number of menses in the 16 weeks before will be considered to report the frequency of menstrual cycles | 16 weeks after the start of the treatment | 
| Change in hirsutism | Modified Ferriman-Gallwey score will be used to measure changes in hirsutism; the minimum and maximum values are 4 and 36 respectively; higher score means a worse outcome | 16 weeks after the start of the treatment | 
| Change in plasma concentrations of testosterone | testosterone will be reported in ng/mL | 16 weeks after the start of the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketogenic diet, PCOS, Insulin resistance, Obesity, Hyperandrogenism