KEtogenic Diet and Its Multiple EffectS on Obesity

Study Overview
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Brief Summary
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The prevalence of obesity and metabolic disturbances is worryingly increasing worldwide, therefore the study of their pathophysiology is extremely important to find new strategies for their treatment. Obesity has a strong impact not only on the metabolism of the patients, but also may impact hormonal, inflammatory and immune profile, and profoundly influence the daily life of the patients. Weight loss may determine an amelioration of these parameters, but the impact of the diet composition aimed to weight loss on them has not been profoundly studied yet. The aim of our research project is to study the effects of a ketogenic diet in comparison with an isocaloric balanced diet on weight loss and anthropometric parameters, quality of life, hormone profile, sleep, sexual function, circadian rhythm, inflammatory and immunological parameters in obese patients.

Official Title
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Comparison of the Effects of a Ketogenic Diet and an Isocaloric Balanced Diet in Obese Patients: a Randomized Clinical Trial

Conditions
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Obesity

Intervention / Treatment
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* Other: Ketogenic diet
* Other: Balanced diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 65 years BMI≥ 30 Kg/m2 Exclusion Criteria: Type 1 diabetes mellitus and latent autoimmune diabetes in adults β-cell failure in type 2 diabetes mellitus Use of sodium/glucose cotransporter 2 (SGLT2) inhibitors Pregnancy and breastfeeding Kidney failure and moderate-to-severe chronic kidney disease Liver failure Heart failure (NYHA III-IV) Respiratory failure Unstable angina, stroke or myocardial infarction in the last 12 months Cardiac arrhythmias Eating disorders and other severe mental illnesses, alcohol and substance abuse Active/severe infections Planned elective surgery or invasive procedures Rare disorders: porphyria, carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine-acylcarnitine translocase deficiency, mitochondrial fatty acid β-oxidation disorders, pyruvate carboxylase deficiency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: Patients are sequentially allocated to one of the 2 arms of intervention: the ketogenic diet arm or the balanced diet arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic diet arm<br>Ketogenic diet for a month, or a longer period if clinically necessary | Other: Ketogenic diet<br>* Prescription of a ketogenic diet, 1200 Kcal/die. Patients are encouraged to walk 30 minutes every day.<br>|
| Active Comparator: Balanced diet arm<br>Balanced diet for a month, or a longer period if clinically necessary | Other: Balanced diet<br>* Prescription of a balanced diet, 1200 Kcal/die. Patients are encouraged to walk 30 minutes every day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of changes in Perceived Quality of Life with IWQOL-Lite Questionnaires | Assessment with the questionnaires Impact of weight/Quality of Life-Lite (IWQOL-Lite); global scale from 0 to 100; the higher the score, the better the quality of life | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes in Perceived Quality of Life with SF-36 Questionnaires | Assessment with the questionnaires Short Form Health Survey 36 (SF-36); scale of every item from 0 to 100; the higher the score, the better the quality of life | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes in Perceived Quality of Life with EQ-5D Questionnaires | Assessment with the questionnaires EQ-5D; scale of every item from 1 to 5; the higher the score, the worse the perceived problem | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of weight loss | Weight loss expressed in Kg | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes of perceived sleep | Assessment with the questionnaires Pittsburgh Sleep Quality Index; global score on a scale from 0 to 21; the higher the score, the worse the sleep quality | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes of perceived sleepiness | Assessment with the questionnaires Epworth Sleepiness Scale (ESS); score on a scale from 0 to 24; the higher the score, the higher the sleepiness | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes in clock genes expression | Evaluation of the expression of the clock genes in blood cells | At baseline, at 30 days | 
| Evaluation of changes in hormonal profile | Assessment of hormonal parameters, as cortisol, expressed in ug/dL | At baseline, at 30 days | 
| Evaluation of changes in sexual function in males | Assessed with the questionnaires International Index of Erectile Function (IIEF-5); scale from 5 to 25; the higher the score, the better the erectile function | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes in inflammation | Measurements of circulating cytokines, as interleukin 2 and interleukin 10, expressed in ng/mL | At baseline, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes of peripheral blood mononuclear cells | Number of cells of peripheral blood mononuclear cell subpopulations, expressed in number/mm3 | At baseline, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes in sleep parameters (length) | Assessment with actigraphy of latency, total minutes in bed, total sleep time, wake after sleep onset, average awakening length, expressed in minutes | At baseline, at 30 days | 
| Evaluation of changes in hip circumference | Assessment of hip circumference, expressed in cm | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes in waist circumference | Assessment of waist circumference, expressed in cm | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Change in circadian rhythm | Evaluation of change in midpoint of sleep, bedtime, sleep onset, rise time and circadian phase, expressed in hours | At baseline, at 30 days | 
| Evaluation of changes in Sexual Function in Females | Assessed with the questionnaire Female Sexual Function Index (FSFI); scale of every item from 1 to 5; the higher score, the better the sexual function | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of changes in sleep efficiency | Sleep efficiency expressed as a percentage; measurement with actigraphy | At baseline, at 30 days | 
| Evaluation of changes in number of awakenings | Measurement with actigraphy | At baseline, at 30 days | 
| Evaluation of changes in sleep parameters | Evaluation of sleep fragmentation index and movement index, with actigraphy | At baseline, at 30 days | 
| Evaluation of changes in metabolic parameters | Evaluation of changes in metabolic parameters, as glucose, triglycerides, cholesterol and HDL, expressed in mmol/L | At baseline, at 30 days | 
| Evaluation of changes in BMI | Weight and height will be combined to report BMI in kg/m^2 | At baseline, at 15 days, at 30 days, at 60 days if the patient continued the diet | 
| Evaluation of height | Assessment of height, expressed in cm | At baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, metabolism, circadian rhythm, sleep, quality of life, balanced diet, ketogenic diet, immune profile