Th Effect of Ketogenic Metabolic Nutritional Pattern on High-frequency Episodic Migraine (EMIKETO)

Study Overview
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Brief Summary
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The study aims to investigate the impact of 2 nutritional patterns on high-frequency episodic migraine. Subjects enrolled will be randomized in two arms: a) very-low-calorie-ketogenic-diet (VLCKD), b) hypocaloric balanced non ketogenic-diet (HBD).

Detailed Description
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This randomized controlled trial aims to: investigate the impact of very-low-calorie-ketogenic-diet (VLCKD) compared to hypocaloric balanced non ketogenic-diet (HBD) on high-frequency episodic migraine evaluate the impact of VLCKD or HBD on immune system, with particular regard to inflammatory and regulatory T cells assess aldosterone blood levels before and after VLCKD or HBD treatment The randomization will be carry out at the single center using an a proper software. All the eligible subjects (please, see the inclusion and exclusion criteria), will be randomized in two groups. Both VLCKD or HBD will be undergone to 24 weeks of diet. For VLCKD- group, the ketogenic period will be maintained for 8 weeks. In the following four weeks, carbohydrates are gradually reintroduced, starting from foods with the lowest glycemic index (fruit, dairy products), followed by foods with moderate and high glycemic index (bread, pasta and cereals). The goal is to achieve a hypocaloric balanced diet (HBD), as well as the controlled group. From the 12th week to the 24 th week, all subjects enrolled will continue follow-up with HBD. Periodically, subjects will be monitored through physical examination (anthropometric measurements, blood pressure, heart rate, etc.) and laboratory analysis.

Official Title
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Randomized-controlled Study for Evaluation of Ketogenic Metabolic Nutritional Pattern in Subjects With High-frequency Episodic Migraine

Conditions
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Migraine, Ketogenic Dieting, Weight Loss, Overweight, Brain Diseases

Intervention / Treatment
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* Dietary Supplement: very-low-calorie-ketogenic-diet
* Other: hypocaloric-balanced-diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index >27 kg/m2 Migraine onset <50 years with monthly frequency of 8-14 days in the last 3 months Absence of prophylaxis therapy for migraine in the previous 3 months Signing of the informed consent Agreement to follow all study procedures, including follow-up visits Negative pregnancy test, performed on urine sample Use of contraceptive method for all participants throughout the duration of the study Agreement for all study participants not to publish study information Exclusion Criteria: Body mass index> 35 kg / m2; prophylaxis treatment for migraine in the previous 3 months antidepressant and neuroleptic drugs treatment during the study (including follow-up) non-potassium-sparing diuretics treatment during the study (including follow-up) Use or implantation of stimulators for migraine Migraine with or without excessive drug use, tension-type headache, cluster headache, sporadic or familial hemiplegic migraine, ophthalmoplegic migraine, basic migraine defined according to the ICHD-3 beta classification in the previous 3 months head trauma psychiatric diseases that can influence adherence to treatment Type I diabetes mellitus or type II diabetes mellitus treated with insulin therapy Taking supplements which affect weight Taking supplements containing sugars in their composition Pregnancy or breastfeeding Abuse of alcohol Other neurological, cardiovascular, liver, respiratory, hematologic, autoimmune diseases or alterations to laboratory tests that could compromise the study

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Very-low-calorie-ketogenic-diet<br>Very-low-calorie-ketogenic-diet (VLCKD) for 12 weeks; hypocaloric-balanced-diet (HBD) | Dietary Supplement: very-low-calorie-ketogenic-diet<br>* VLCKD-group will undergone to VLCKD for 8 weeks. VLCKD is based on protein preparations of high biological value. Total daily energy intake is < 800 kcal.Daily carbohydrate intake is lower than 30 g/day, while daily protein intake is approximately 1.2-1.5 g/kg of ideal body weight. The following four weeks, carbohydrates are gradually reintroduced, starting from foods with the lowest glycemic index (fruit, dairy products), followed by foods with moderate and high glycemic index (bread, pasta and cereals). The goal is to achieve a hypocaloric balanced diet (HBD), as well as the controlled group. From the 12th week to the 24 th week, all subjects enrolled will continue follow-up with HBD.<br>|
| Active Comparator: Hypocaloric-balanced-diet<br>Hypocaloric-balanced-diet (HBD) | Other: hypocaloric-balanced-diet<br>* HBD-group will undergone to hypo caloric balanced diet for 24 weeks. Total daily average energy intake is 1500-1600 kcal/day. 30% of total daily energy is composed by lipids (10% MUFA, 10% PUFA, 10% SFA), 55% carbohydrates, while daily protein intake is approximately 0.8-1.5 g /kg of ideal body weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in migraine frequency | Migraine Disability Assessment Score Questionnaire (MIDAS) is used in order to evaluate how severity migraine affects patient's life. MIDAS score: 0-25 | at baseline (V2), at 8 weeks- the end ok ketogenic period (V5) and at 12 weeks-the end of diet (V6) and at 24 weeks -the end of follow-up (V7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of migraine episode on daily activities | Headache Impact Test (HIT-6) is used in order to determine how severely migraine impacts on daily activities. HIT-6 total score: 36-78 | at baseline (V2), at 8 weeks- the end ok ketogenic period (V5) and at 12 weeks-the end of diet (V6) and at 24 weeks -the end of follow-up (V7) | 
| Weight loss | Physical examination will be carried out in each visit. Weight will be detected | at baseline (V2), at 8 weeks- the end ok ketogenic period (V5) and at 12 weeks-the end of diet (V6) and at 24 weeks -the end of follow-up (V7) | 
| Change in immune system parameters | Immune system plays a key role in overweight subjects susceptibility to inflammatory diseases. Lymphocyte subpopulation will be studied before and after VLCKD or HBD through blood tests. | at the screening (V1),at 8 weeks- the end ok ketogenic period (V5) and at 12 weeks-the end of diet (V6) | 
| Health-related quality of life | Health Survey-36 (SF-36) is used in order to evaluate the impact of migraine on quality of life. SF-36 score: The SF-36, as described in the name, is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state. | at baseline (V2), at 8 weeks- the end ok ketogenic period (V5) and at 12 weeks-the end of diet (V6) | 
| change in analgesic consumption | On migraine-diary, subjects will reported analgesic consumption during diet-treatment | through study completion, an average of 24 weeks | 
| Measure of pain | Visual analogue scale (VAS) is used in order to evaluate pain intensity. VAS score: 0-10 | at baseline (V2), at 8 weeks- the end ok ketogenic period (V5) and at 12 weeks-the end of diet (V6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VLCKD, migraine, diet, weight loss, ketone bodies, inflammatory state