Neurophysiological and Biomolecular Effects of Atogepant in Episodic Migraine

NCT06882122 | Recruiting

• 1 other identifier: ATOM
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators aim to assess and compare neurophysiological and biochemical changes induced by a 3-month treatment with atogepant (60 mg daily) in patients with high-frequency episodic migraine (8-14 monthly migraine days). Evaluations will include neurophysiological assessments (High-Density EEG, nociceptive reflexes, and visual evoked potentials) and biomolecular profiling (gene expression of endocannabinoid catabolizing enzymes, CGRP and PACAP plasma levels, and headache-specific microRNAs). Outputs will contribute to defining predictors of atogepant response, elucidating its effects on brain connectivity, excitability, and CGRP/endocannabinoid pathways, and identifying alternative therapeutic targets for non-responders.

Conditions

Migraine Disorder; Episodic Migraine

Keywords

Migraine; Gepants; endocannabinoid system; MicroRNAs; Habituation deficit; Central sensitization; Functional Connectivity

Outcome Measures

Primary Outcomes (2)

• Temporal summation threshold of the RIII reflex (continuos variable)

  Temporal summation threshold of the RIII reflex will be used to assess central sensitization after 3 months of treatment with atogepant 60 mg/day compared to baseline.

  Baseline (T0) - three months of atogepant 60 mg treatment (T1)

• MAGL gene expression (continuos variable)

  Changes in MAGL gene expression after 3 months of treatment with atogepant 60 mg/day

  Baseline (T0) - three months of atogepant 60 mg treatment (T1)

Secondary Outcomes (7)

• Habituation index of the nociceptive Blink Reflex (continuous variable)

  Baseline (T0) - three months of atogepant 60 mg treatment (T1)

• Habituation of the visual evoked potential (continuous variable)

  Baseline (T0) - three months of atogepant 60 mg treatment (T1)

• Functional brain connectivity (continuous variable)

  Baseline (T0) - three months of atogepant 60 mg treatment (T1)

• FAAH gene expression (continuous variable)

  Baseline (T0) - three months of atogepant 60 mg treatment (T1)

• Plasma levels of CGRP (continuous variable)

  Baseline (T0) - three months of atogepant 60 mg treatment (T1)

Study Arms (1)

HFEM group

High-frequency episodic migraine patients (8-14 migraine days per months) undergoing atogepant 60 mg daily for 3 months

Drug: Atogepant 60 mg

Interventions

Atogepant 60 mg DRUG

Atogepant 60 mg daily for 3 months

HFEM group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects with high frequency episodic migraine attending the outpatient clinic of the Headache Science \& Neurorehabilitation Center of the IRCCS Mondino Foundation (Pavia, Italy).

You may qualify if:

• Individuals aged between 18 and 70;
• Diagnosis of episodic migraine according to ICHD-3 criteria;
• Monthly migraine days between 8 and 14 (high-frequency episodic migraine pattern) in the 3 months before screening;
• Individuals naïve to CGRP-targeted treatments;
• No more than one ongoing migraine preventive treatment with a stable dose for at least 3 months.

You may not qualify if:

• Contraindications to atogepant;
• History of serious psychiatric conditions;
• Diagnosis of other primary or secondary headaches (only sporadic tension-type headache is allowed);
• Medical conditions considered clinically significant by the investigator;
• Chronic pain conditions that need chronic treatment;
• Abuse of alcohol and/or drugs;
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead

Study Sites (1)

Headache Science & Neurorehabilitation Center

Pavia, PAVIA, 27100, Italy

RECRUITING

Related Publications (16)

• Greco R, De Icco R, Demartini C, Zanaboni AM, Tumelero E, Sances G, Allena M, Tassorelli C. Plasma levels of CGRP and expression of specific microRNAs in blood cells of episodic and chronic migraine subjects: towards the identification of a panel of peripheral biomarkers of migraine? J Headache Pain. 2020 Oct 16;21(1):122. doi: 10.1186/s10194-020-01189-0.

  PMID: 33066724 BACKGROUND

• Andersen HH, Duroux M, Gazerani P. Serum MicroRNA Signatures in Migraineurs During Attacks and in Pain-Free Periods. Mol Neurobiol. 2016 Apr;53(3):1494-1500. doi: 10.1007/s12035-015-9106-5. Epub 2015 Feb 1.

  PMID: 25636687 BACKGROUND

• 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

• Greco R, Demartini C, Zanaboni AM, Francavilla M, De Icco R, Ahmad L, Tassorelli C. The endocannabinoid system and related lipids as potential targets for the treatment of migraine-related pain. Headache. 2022 Mar;62(3):227-240. doi: 10.1111/head.14267. Epub 2022 Feb 18.

  PMID: 35179780 BACKGROUND

• de Tommaso M, Ambrosini A, Brighina F, Coppola G, Perrotta A, Pierelli F, Sandrini G, Valeriani M, Marinazzo D, Stramaglia S, Schoenen J. Altered processing of sensory stimuli in patients with migraine. Nat Rev Neurol. 2014 Mar;10(3):144-55. doi: 10.1038/nrneurol.2014.14. Epub 2014 Feb 18.

  PMID: 24535465 BACKGROUND

• Ambrosini A, Kisialiou A, Schoenen J. Visual and auditory cortical evoked potentials in interictal episodic migraine: An audit on 624 patients from three centres. Response to the letter by Omland et al. Cephalalgia. 2017 Oct;37(12):1209-1210. doi: 10.1177/0333102416680616. Epub 2016 Nov 21. No abstract available.

  PMID: 27872339 BACKGROUND

• Perrotta A, Anastasio MG, De Icco R, Coppola G, Ambrosini A, Serrao M, Sandrini G, Pierelli F. Frequency-Dependent Habituation Deficit of the Nociceptive Blink Reflex in Aura With Migraine Headache. Can Migraine Aura Modulate Trigeminal Excitability? Headache. 2017 Jun;57(6):887-898. doi: 10.1111/head.13111. Epub 2017 May 10.

  PMID: 28488755 BACKGROUND

• Coppola G, Di Lorenzo C, Schoenen J, Pierelli F. Habituation and sensitization in primary headaches. J Headache Pain. 2013 Jul 30;14(1):65. doi: 10.1186/1129-2377-14-65.

  PMID: 23899115 BACKGROUND

• De Icco R, Fiamingo G, Greco R, Bottiroli S, Demartini C, Zanaboni AM, Allena M, Guaschino E, Martinelli D, Putorti A, Grillo V, Sances G, Tassorelli C. Neurophysiological and biomolecular effects of erenumab in chronic migraine: An open label study. Cephalalgia. 2020 Oct;40(12):1336-1345. doi: 10.1177/0333102420942230. Epub 2020 Jul 26.

  PMID: 32715736 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

• Lipton RB, Pozo-Rosich P, Blumenfeld AM, Li Y, Severt L, Stokes JT, Creutz L, Gandhi P, Dodick D. Effect of Atogepant for Preventive Migraine Treatment on Patient-Reported Outcomes in the Randomized, Double-blind, Phase 3 ADVANCE Trial. Neurology. 2023 Feb 21;100(8):e764-e777. doi: 10.1212/WNL.0000000000201568. Epub 2022 Nov 17.

  PMID: 36396451 BACKGROUND

• Rissardo JP, Caprara ALF. Gepants for Acute and Preventive Migraine Treatment: A Narrative Review. Brain Sci. 2022 Nov 24;12(12):1612. doi: 10.3390/brainsci12121612.

  PMID: 36552072 BACKGROUND

• Pozo-Rosich P, Ailani J, Ashina M, Goadsby PJ, Lipton RB, Reuter U, Guo H, Schwefel B, Lu K, Boinpally R, Miceli R, De Abreu Ferreira R, McCusker E, Yu SY, Severt L, Finnegan M, Trugman JM. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Sep 2;402(10404):775-785. doi: 10.1016/S0140-6736(23)01049-8. Epub 2023 Jul 26.

  PMID: 37516125 BACKGROUND

• Goadsby PJ, Dodick DW, Ailani J, Trugman JM, Finnegan M, Lu K, Szegedi A. Safety, tolerability, and efficacy of orally administered atogepant for the prevention of episodic migraine in adults: a double-blind, randomised phase 2b/3 trial. Lancet Neurol. 2020 Sep;19(9):727-737. doi: 10.1016/S1474-4422(20)30234-9.

  PMID: 32822633 BACKGROUND

• Ailani J, Lipton RB, Goadsby PJ, Guo H, Miceli R, Severt L, Finnegan M, Trugman JM; ADVANCE Study Group. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021 Aug 19;385(8):695-706. doi: 10.1056/NEJMoa2035908.

  PMID: 34407343 BACKGROUND

• Buse DC, Armand CE, Charleston L 4th, Reed ML, Fanning KM, Adams AM, Lipton RB. Barriers to care in episodic and chronic migraine: Results from the Chronic Migraine Epidemiology and Outcomes Study. Headache. 2021 Apr;61(4):628-641. doi: 10.1111/head.14103. Epub 2021 Apr 1.

  PMID: 33797078 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood

MeSH Terms

Conditions

Migraine Disorders

Interventions

atogepant

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Francescantonio Cammarota, MD

CONTACT

00390382380425; francesco.cammarota@mondino.it

Cinzia Fattore

CONTACT

00390382380385; cinzia.fattore@mondino.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 18, 2025
• Study Start: December 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: April 1, 2026
• Last Updated: March 18, 2025

Record last verified: 2025-03

Locations

IT (1)