Chronology and Sequence of Premonitory Symptoms

NCT07681466 | Recruiting

• 1 other identifier: CHRONO-PS-26
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to prospectively investigate the temporal sequence of premonitory symptoms across multiple migraine attacks.

Conditions

Migraine

Keywords

premonitory symptoms; sequence; hypothalamus; chronology; disability

Outcome Measures

Primary Outcomes (1)

• Frequency of each symptom as the first premonitory symptom

  Premonitory symptoms will be recorded at the beginning of each migraine attack for a maximum of 5 migraine attacks per participant. For each premonitory symptom, the percentage of recorded attacks in which it was reported as the first symptom of the premonitory phase. Symptoms are recorded at headache onset for each attack via a structured electronic diary, capturing the type, sequence, onset, and duration of symptoms preceding the pain phase. The denominator is the number of recorded attacks with a premonitory phase.

  Up to 6 months

Secondary Outcomes (7)

• Time from onset of each premonitory symptom to headache onset (categorical intervals)

  up to 6 months

• Time from onset of each premonitory symptom to headache onset (minutes)

  Up to 6 months

• Intra-subject consistency of premonitory symptoms across attacks

  Up to 6 months

• Evolution and persistence of premonitory symptoms during the headache phase

  Up to 6 months

• Patient-level agreement between clinically reported and prospectively recorded presence of premonitory symptoms

  Up to 6 months

Other Outcomes (1)

• Patterns of premonitory symptom transition and clustering

  Up to 6 months

Study Arms (1)

patients with migraine

episodic migraine or chronic migraine or migraine with aura

Eligibility Criteria

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

Study Population

Prospective, longitudinal, multicentric study on patients with migraine attending the outpatient clinic of Italian Headache centres who will meet the inclusion and exclusion criteria.

You may qualify if:

• Diagnosis of episodic (EM) or chronic migraine (CM) or CM with medication overuse headache (MOH) according to ICHD-III criteria;
• Age between 18 and 65 years;
• Signed written informed consent.

You may not qualify if:

• History or current diagnosis of secondary headache disorders as defined by ICHD-III;
• History of other neurological comorbidities or major psychiatric disorders;
• Opioid overuse according to the ICHD-III criteria;
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• University of Roma La Sapienza: lead
• IRCCS National Neurological Institute "C. Mondino" Foundation: collaborator
• University of Modena and Reggio Emilia: collaborator
• University of Bari: collaborator
• Campus Bio-Medico University: collaborator
• Azienda Ospedaliera Universitaria Mater Domini, Catanzaro: collaborator
• Azienda USL Ferrara: collaborator
• University of Florence: collaborator
• Azienda Ospedaliero-Universitaria Careggi: collaborator
• Azienda Ospedaliero Universitaria Policlinico Modena: collaborator
• Ospedale di Piove di Sacco: collaborator
• Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari: collaborator
• Cliniche Humanitas Gavazzeni: collaborator
• Carlo Besta Neurological Institute: collaborator

Study Sites (1)

Sapienza University of Rome, Polo Pontino, centro cefalee, ICOT

Latina, Italy, 04100, Italy

RECRUITING

Related Publications (5)

• Dodick DW, Goadsby PJ, Schwedt TJ, Lipton RB, Liu C, Lu K, Yu SY, Severt L, Finnegan M, Trugman JM. Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA. Lancet. 2023 Dec 16;402(10419):2307-2316. doi: 10.1016/S0140-6736(23)01683-5. Epub 2023 Nov 15.

  PMID: 37979595 BACKGROUND

• Messina R, Rocca MA, Goadsby PJ, Filippi M. Insights into migraine attacks from neuroimaging. Lancet Neurol. 2023 Sep;22(9):834-846. doi: 10.1016/S1474-4422(23)00152-7. Epub 2023 Jul 18.

  PMID: 37478888 BACKGROUND

• Karsan N, Goadsby PJ. Neuroimaging in the pre-ictal or premonitory phase of migraine: a narrative review. J Headache Pain. 2023 Aug 11;24(1):106. doi: 10.1186/s10194-023-01617-x.

  PMID: 37563570 BACKGROUND

• Eigenbrodt AK, Christensen RH, Ashina H, Iljazi A, Christensen CE, Steiner TJ, Lipton RB, Ashina M. Premonitory symptoms in migraine: a systematic review and meta-analysis of observational studies reporting prevalence or relative frequency. J Headache Pain. 2022 Nov 12;23(1):140. doi: 10.1186/s10194-022-01510-z.

  PMID: 36371152 BACKGROUND

• Sebastianelli G, Atalar AC, Cetta I, Farham F, Fitzek M, Karatas-Kursun H, Kholodova M, Kukumagi KH, Montisano DA, Onan D, Pantovic A, Skarlet J, Sotnikov D, Caronna E, Pozo-Rosich P; International Headache Academy of the International Headache Society (IHS-iHEAD). Insights from triggers and prodromal symptoms on how migraine attacks start: The threshold hypothesis. Cephalalgia. 2024 Oct;44(10):3331024241287224. doi: 10.1177/03331024241287224.

  PMID: 39380339 BACKGROUND

MeSH Terms

Conditions

Migraine Disorders

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Gabriele Sebastianelli, MD

CONTACT

+393926337082; gabriele.sebastianelli@uniroma1.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: June 20, 2026
• First Posted: July 2, 2026
• Study Start: March 17, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: July 2, 2026

Record last verified: 2026-06

Locations

IT (1)