Searching for Novel Therapeutic Approaches in Migraine Patients Resistant to Treatments

NCT06562400 | Recruiting

• 1 other identifier: SPHERA - WP2
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Primary working hypothesis is that NON-responders to mAbs bear a dysfunction of the endocannabidiome system (eCBome), as suggested by pre-clinical and clinical data by our group. They will be identified as patients showing a reduction of monthly migraine days \< 50% after three months of treatment. The clinical, biochemical and neurofunctional impact of novel therapeutic approaches expected to interfere with eCBome will be evaluated in NON-responder patients

Conditions

Migraine Disorders; Chronic Migraine; Episodic Migraine

Keywords

migraine; anti CGRP mABs; calcitonin gene related peptide; endocannabinoid system; HD EEG; functional MRI; brain connectivity; miocrobiome

Outcome Measures

Primary Outcomes (1)

• Monthly migraine days (MMDs)

  MMDs during treatment with PEA or KD (continuous variable)

  Baseline (V0), after three months of intervention (V1), after six months of intervention (V2)

Secondary Outcomes (6)

• Monthly headache days (MHDs)

  Baseline (V0), after three months of intervention (V1), after six months of intervention (V2)

• Monthly days and doses of acute drug intake

  Baseline (V0), after three months of intervention (V1), after six months of intervention (V2)

• Percentage of patients with a 50% reduction in MMDs

  Baseline (V0), after three months of intervention (V1), after six months of intervention (V2)

• Migraine related disability assessed by means of MIDAS

  Baseline (V0), after three months of intervention (V1), after six months of intervention (V2)

• Headache impact assessed by means of HIT-6

  Baseline (V0), after three months of intervention (V1), after six months of intervention (V2)

Study Arms (2)

NON-Responders

Patients with high frequency episodic or chronic migraine who obtained a reduction in monthly migraine days \< 50% after three months of mAbs treatment compared to pre-treatment values.

Dietary Supplement: Palmitoyl ethanolamide; Behavioral: Ketogenic diet

Partial-Responders

Patients with high frequency episodic or chronic migraine who obtained a reduction in monthly migraine days \> or equal to 50% after six months of mAbs treatment compared to pre-treatment values but still present more than 5 MMDs.

Dietary Supplement: Palmitoyl ethanolamide

Interventions

Palmitoyl ethanolamide DIETARY_SUPPLEMENT

PEA supplementation (600mg twice a day for three months)

Also known as: PEA

NON-Responders; Partial-Responders

Ketogenic diet BEHAVIORAL

Diet characterized by the following percentages of macronutrients: 65% fat, 27% protein and 8% carbohydrates

Also known as: KD

NON-Responders

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects with chronic and high frequency episodic migraine attending the outpatient clinic of the Headache Science \& Neurorehabilitation Unit of the IRCCS Mondino Foundation (Pavia, Italy) and the Neurology Department of the University of L'Aquila (Avezzano, Italy).

You may qualify if:

• male and female patients aged 18 to 75 years
• diagnosis of episodic migraine or chronic migraine according to ICHD-3 criteria
• for episodic migraine: 8-14 monthly migraine days in the previous 3 months
• diagnosis of resistant migraine, defined by having failed at least 3 classes of migraine preventatives and suffer from at least 8 debilitating monthly headache days for at least 3 consecutive months
• patients naive to CGRP targeting treatments

You may not qualify if:

• history of major psychiatric or other neurological conditions
• diagnosis of other primary or secondary headache disorders (only sporadic tension-type headache is allowed if the patients can clearly differentiate between the 2 types of headaches)
• clinically significant medical conditions
• chronic pain conditions
• alcohol and/or drug abuse
• pregnancy or lactation

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead
• University of L'Aquila: collaborator

Study Sites (1)

Headache Science & Neurorehabilitation Unit

Pavia, 27100, Italy

RECRUITING

Related Publications (11)

• Greco R, Demartini C, Zanaboni AM, Tumelero E, Icco R, Sances G, Allena M, Tassorelli C. Peripheral changes of endocannabinoid system components in episodic and chronic migraine patients: A pilot study. Cephalalgia. 2021 Feb;41(2):185-196. doi: 10.1177/0333102420949201. Epub 2020 Sep 23.

  PMID: 32967434 BACKGROUND

• De Icco R, Greco R, Demartini C, Vergobbi P, Zanaboni A, Tumelero E, Reggiani A, Realini N, Sances G, Grillo V, Allena M, Tassorelli C. Spinal nociceptive sensitization and plasma palmitoylethanolamide levels during experimentally induced migraine attacks. Pain. 2021 Sep 1;162(9):2376-2385. doi: 10.1097/j.pain.0000000000002223.

  PMID: 33587406 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

• Bongiovanni D, Benedetto C, Corvisieri S, Del Favero C, Orlandi F, Allais G, Sinigaglia S, Fadda M. Effectiveness of ketogenic diet in treatment of patients with refractory chronic migraine. Neurol Sci. 2021 Sep;42(9):3865-3870. doi: 10.1007/s10072-021-05078-5. Epub 2021 Feb 1.

  PMID: 33527209 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

• Paulus MP, Stein MB, Simmons AN, Risbrough VB, Halter R, Chaplan SR. The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial. Neuropsychopharmacology. 2021 Apr;46(5):1011-1019. doi: 10.1038/s41386-020-00936-w. Epub 2020 Dec 17.

  PMID: 33335310 BACKGROUND

• Deng H, Li W. Monoacylglycerol lipase inhibitors: modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders. Acta Pharm Sin B. 2020 Apr;10(4):582-602. doi: 10.1016/j.apsb.2019.10.006. Epub 2019 Oct 18.

  PMID: 32322464 BACKGROUND

• Chirchiglia D, Cione E, Caroleo MC, Wang M, Di Mizio G, Faedda N, Giacolini T, Siviglia S, Guidetti V, Gallelli L. Effects of Add-On Ultramicronized N-Palmitol Ethanol Amide in Patients Suffering of Migraine With Aura: A Pilot Study. Front Neurol. 2018 Aug 17;9:674. doi: 10.3389/fneur.2018.00674. eCollection 2018.

  PMID: 30177906 BACKGROUND

• Papetti L, Sforza G, Tullo G, Alaimo di Loro P, Moavero R, Ursitti F, Ferilli MAN, Tarantino S, Vigevano F, Valeriani M. Tolerability of Palmitoylethanolamide in a Pediatric Population Suffering from Migraine: A Pilot Study. Pain Res Manag. 2020 Apr 24;2020:3938640. doi: 10.1155/2020/3938640. eCollection 2020.

  PMID: 32377286 BACKGROUND

• Freitas HR, Isaac AR, Malcher-Lopes R, Diaz BL, Trevenzoli IH, De Melo Reis RA. Polyunsaturated fatty acids and endocannabinoids in health and disease. Nutr Neurosci. 2018 Dec;21(10):695-714. doi: 10.1080/1028415X.2017.1347373. Epub 2017 Jul 7.

  PMID: 28686542 BACKGROUND

• Perrotta A, Arce-Leal N, Tassorelli C, Gasperi V, Sances G, Blandini F, Serrao M, Bolla M, Pierelli F, Nappi G, Maccarrone M, Sandrini G. Acute reduction of anandamide-hydrolase (FAAH) activity is coupled with a reduction of nociceptive pathways facilitation in medication-overuse headache subjects after withdrawal treatment. Headache. 2012 Oct;52(9):1350-61. doi: 10.1111/j.1526-4610.2012.02170.x. Epub 2012 Jun 1.

  PMID: 22670561 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood

MeSH Terms

Conditions

Migraine Disorders

Interventions

palmidrol; Diet, Ketogenic

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Central Study Contacts

Roberto De Icco

CONTACT

00390382380425; roberto.deicco@mondino.it

Cinzia Fattore

CONTACT

00390382380385; cinzia.fattore@mondino.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2024
• First Posted: August 20, 2024
• Study Start: May 10, 2023
• Primary Completion: October 1, 2024
• Study Completion: May 1, 2026
• Last Updated: August 20, 2024

Record last verified: 2024-08

Locations

IT (1)