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

NCT04360148 | Unknown

• 1 other identifier: RP 19/23
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Migraine; Ketogenic Dieting; Weight Loss; Overweight; Brain Diseases

Keywords

VLCKD; migraine; diet; weight loss; ketone bodies; inflammatory state

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Impact of migraine episode on daily activities

  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

  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

  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

  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

  through study completion, an average of 24 weeks

Study Arms (2)

Very-low-calorie-ketogenic-diet

EXPERIMENTAL

Very-low-calorie-ketogenic-diet (VLCKD) for 12 weeks; hypocaloric-balanced-diet (HBD)

Dietary Supplement: very-low-calorie-ketogenic-diet

Hypocaloric-balanced-diet

ACTIVE COMPARATOR

Hypocaloric-balanced-diet (HBD)

Other: hypocaloric-balanced-diet

Interventions

very-low-calorie-ketogenic-diet DIETARY_SUPPLEMENT

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.

Very-low-calorie-ketogenic-diet

hypocaloric-balanced-diet OTHER

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.

Hypocaloric-balanced-diet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• New Penta SRL: lead
• IRCCS San Raffaele: collaborator

Study Sites (1)

IRCCS San Raffaele Pisana

Rome, 00163, Italy

Location

Related Publications (25)

• GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 2017 Nov;16(11):877-897. doi: 10.1016/S1474-4422(17)30299-5. Epub 2017 Sep 17.

  PMID: 28931491 BACKGROUND

• Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF; AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007 Jan 30;68(5):343-9. doi: 10.1212/01.wnl.0000252808.97649.21.

  PMID: 17261680 BACKGROUND

• Bigal ME, Lipton RB, Holland PR, Goadsby PJ. Obesity, migraine, and chronic migraine: possible mechanisms of interaction. Neurology. 2007 May 22;68(21):1851-61. doi: 10.1212/01.wnl.0000262045.11646.b1.

  PMID: 17515549 BACKGROUND

• Bond DS, Roth J, Nash JM, Wing RR. Migraine and obesity: epidemiology, possible mechanisms and the potential role of weight loss treatment. Obes Rev. 2011 May;12(5):e362-71. doi: 10.1111/j.1467-789X.2010.00791.x.

  PMID: 20673279 BACKGROUND

• Peterlin BL, Sacco S, Bernecker C, Scher AI. Adipokines and Migraine: A Systematic Review. Headache. 2016 Apr;56(4):622-44. doi: 10.1111/head.12788. Epub 2016 Mar 25.

  PMID: 27012149 BACKGROUND

• Yumuk V, Tsigos C, Fried M, Schindler K, Busetto L, Micic D, Toplak H; Obesity Management Task Force of the European Association for the Study of Obesity. European Guidelines for Obesity Management in Adults. Obes Facts. 2015;8(6):402-24. doi: 10.1159/000442721. Epub 2015 Dec 5.

  PMID: 26641646 BACKGROUND

• Basciani S, Costantini D, Contini S, Persichetti A, Watanabe M, Mariani S, Lubrano C, Spera G, Lenzi A, Gnessi L. Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet. Endocrine. 2015 Apr;48(3):863-70. doi: 10.1007/s12020-014-0355-2. Epub 2014 Jul 26.

  PMID: 25063307 BACKGROUND

• Ellulu MS, Patimah I, Khaza'ai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017 Jun;13(4):851-863. doi: 10.5114/aoms.2016.58928. Epub 2016 Mar 31.

  PMID: 28721154 BACKGROUND

• Lutas A, Yellen G. The ketogenic diet: metabolic influences on brain excitability and epilepsy. Trends Neurosci. 2013 Jan;36(1):32-40. doi: 10.1016/j.tins.2012.11.005. Epub 2012 Dec 8.

  PMID: 23228828 BACKGROUND

• Klosinski LP, Yao J, Yin F, Fonteh AN, Harrington MG, Christensen TA, Trushina E, Brinton RD. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease. EBioMedicine. 2015 Nov 3;2(12):1888-904. doi: 10.1016/j.ebiom.2015.11.002. eCollection 2015 Dec.

  PMID: 26844268 BACKGROUND

• Paoli A, Bianco A, Damiani E, Bosco G. Ketogenic diet in neuromuscular and neurodegenerative diseases. Biomed Res Int. 2014;2014:474296. doi: 10.1155/2014/474296. Epub 2014 Jul 3.

  PMID: 25101284 BACKGROUND

• de Almeida Rabello Oliveira M, da Rocha Ataide T, de Oliveira SL, de Melo Lucena AL, de Lira CE, Soares AA, de Almeida CB, Ximenes-da-Silva A. Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats. Neurosci Lett. 2008 Mar 21;434(1):66-70. doi: 10.1016/j.neulet.2008.01.032. Epub 2008 Jan 19.

  PMID: 18281154 BACKGROUND

• Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG, Shaw R, Smith Y, Geiger JD, Dingledine RJ. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol. 2006 Aug;60(2):223-35. doi: 10.1002/ana.20899.

  PMID: 16807920 BACKGROUND

• Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci. 2018 Feb;19(2):63-80. doi: 10.1038/nrn.2017.156. Epub 2018 Jan 11.

  PMID: 29321682 BACKGROUND

• Waeber C, Moskowitz MA. Migraine as an inflammatory disorder. Neurology. 2005 May 24;64(10 Suppl 2):S9-15. doi: 10.1212/wnl.64.10_suppl_2.s9. No abstract available.

  PMID: 15911785 BACKGROUND

• Puchalska P, Crawford PA. Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. Cell Metab. 2017 Feb 7;25(2):262-284. doi: 10.1016/j.cmet.2016.12.022.

  PMID: 28178565 BACKGROUND

• Jeong EA, Jeon BT, Shin HJ, Kim N, Lee DH, Kim HJ, Kang SS, Cho GJ, Choi WS, Roh GS. Ketogenic diet-induced peroxisome proliferator-activated receptor-gamma activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Exp Neurol. 2011 Dec;232(2):195-202. doi: 10.1016/j.expneurol.2011.09.001. Epub 2011 Sep 14.

  PMID: 21939657 BACKGROUND

• Zhang Y, Xu J, Zhang K, Yang W, Li B. The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms. Curr Neuropharmacol. 2018;16(1):66-70. doi: 10.2174/1570159X15666170517153509.

  PMID: 28521671 BACKGROUND

• Kim DY, Hao J, Liu R, Turner G, Shi FD, Rho JM. Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis. PLoS One. 2012;7(5):e35476. doi: 10.1371/journal.pone.0035476. Epub 2012 May 2.

  PMID: 22567104 BACKGROUND

• Yudkoff M, Daikhin Y, Horyn O, Nissim I, Nissim I. Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia. 2008 Nov;49 Suppl 8(Suppl 8):73-5. doi: 10.1111/j.1528-1167.2008.01841.x.

  PMID: 19049594 BACKGROUND

• Di Lorenzo C, Curra A, Sirianni G, Coppola G, Bracaglia M, Cardillo A, De Nardis L, Pierelli F. Diet transiently improves migraine in two twin sisters: possible role of ketogenesis? Funct Neurol. 2013 Oct-Dec;28(4):305-8.

  PMID: 24598400 BACKGROUND

• Di Lorenzo C, Coppola G, Sirianni G, Di Lorenzo G, Bracaglia M, Di Lenola D, Siracusano A, Rossi P, Pierelli F. Migraine improvement during short lasting ketogenesis: a proof-of-concept study. Eur J Neurol. 2015 Jan;22(1):170-7. doi: 10.1111/ene.12550. Epub 2014 Aug 25.

  PMID: 25156013 BACKGROUND

• Di Lorenzo C, Coppola G, Bracaglia M, Di Lenola D, Evangelista M, Sirianni G, Rossi P, Di Lorenzo G, Serrao M, Parisi V, Pierelli F. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain. 2016;17:58. doi: 10.1186/s10194-016-0650-9. Epub 2016 May 31.

  PMID: 27245682 BACKGROUND

• Fery F, Bourdoux P, Christophe J, Balasse EO. Hormonal and metabolic changes induced by an isocaloric isoproteinic ketogenic diet in healthy subjects. Diabete Metab. 1982 Dec;8(4):299-305.

  PMID: 6761185 BACKGROUND

• Caprio M, Moriconi E, Camajani E, Feraco A, Marzolla V, Vitiello L, Proietti S, Armani A, Gorini S, Mammi C, Egeo G, Aurilia C, Fiorentini G, Tomino C, Barbanti P. Very-low-calorie ketogenic diet vs hypocaloric balanced diet in the prevention of high-frequency episodic migraine: the EMIKETO randomized, controlled trial. J Transl Med. 2023 Oct 4;21(1):692. doi: 10.1186/s12967-023-04561-1.

  PMID: 37794395 DERIVED

MeSH Terms

Conditions

Migraine Disorders; Weight Loss; Overweight; Brain Diseases

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Central Nervous System Diseases; Nervous System Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Piero Barbanti, Prof.

  IRCCS San Raffaele Pisana, 00163 Rome-Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 24, 2020
• Study Start: February 6, 2020
• Primary Completion: September 14, 2020
• Study Completion: May 30, 2021
• Last Updated: April 24, 2020

Record last verified: 2020-04

Locations

IT (1)