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NCT Number: NCT07812740

Italian Trigeminal Autonomic Cephalalgias Assessment Study

ITACA is a prospective, multicenter, observational longitudinal cohort study conducted in routine clinical practice at six Italian headache centers. Approximately 800 adults with trigeminal autonomic cephalalgias (cluster headache, paroxysmal hemicrania, SUNCT, SUNA, or hemicrania continua) diagnosed according to ICHD-3 will be enrolled. The study will describe clinical features and real-world treatment patterns and will evaluate treatment effectiveness and tolerability, changes in clinical features over time, comorbidities, lifestyle factors, patient-reported outcomes, and predictors of treatment response and disease progression. No investigational intervention will be assigned; treatments are prescribed by treating physicians as part of routine clinical care. Participants will be assessed at baseline and during routine follow-up visits, approximately every 3-6 months or as clinically indicated, for up to 3 years. Relevant clinical data already available in medical records before enrollment may also be collected to improve baseline characterization and reconstruction of disease course.

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Key information

Conditions

Trigeminal Autonomic Cephalalgias Brain Diseases Central Nervous System Diseases Cluster Headache Headache Disorders Headache Disorders, Primary Hemicrania Continua Nervous System Diseases Paroxysmal Hemicrania SUNCT Short Lasting Unilateral Neuralgiform Headache Attacks

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, MI, 20133, Italy

Location status: Recruiting

Location contact

Danilo A Montisano, MD

CONTACT

[email protected]

+ 39 02.2394

About this study

Trigeminal autonomic cephalalgias are rare and highly disabling primary headache disorders characterized by unilateral pain and ipsilateral cranial autonomic symptoms. Their clinical heterogeneity, frequent misdiagnosis, diagnostic delay, and the limited availability of large longitudinal datasets make accurate phenotypic characterization and evidence-based treatment selection difficult. ITACA is designed to address these gaps through systematic real-world data collection in a multicenter setting.

The study is a prospective, multicenter, observational longitudinal cohort conducted in routine outpatient clinical practice. Recruitment is planned for 3 years, with follow-up for up to 3 years per participant and an overall study duration of approximately 6 years. Consecutive eligible adult outpatients with a diagnosis of cluster headache, paroxysmal hemicrania, SUNCT, SUNA, or hemicrania continua according to ICHD-3 will be invited to participate. Relevant pre-enrollment clinical information already available in medical records may be collected retrospectively at baseline to improve characterization of disease history.

No protocol-mandated treatment or investigational intervention is assigned. Acute and preventive treatments are prescribed independently by treating physicians according to routine clinical practice. Data are collected at baseline and at routine follow-up visits, expected approximately every 3-6 months or whenever clinically indicated. Collected information includes attack frequency, duration and severity, cranial autonomic and other accompanying symptoms, temporal patterns, disease course, treatment history and ongoing treatment exposure, treatment effectiveness and tolerability, adverse events, comorbidities, lifestyle factors, concomitant medications, headache diary information, and patient-reported measures. Questionnaires may include PGIC, ASC-12, EQ-5D, SF-36, CHIQ, HARS, HDRS, HADS, LDQ, and PSQI according to routine practice and local availability. Data are recorded in a standardized electronic case report form using REDCap.

The planned sample size is approximately 800 participants, expected to include about 70-80% with cluster headache and 20-30% with other trigeminal autonomic cephalalgias. Analyses will be primarily descriptive and will include longitudinal and multivariable models to assess clinical characteristics, treatment outcomes, and predictors of response, refractoriness, and disease progression.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 years or older.
  • Diagnosis of trigeminal autonomic cephalalgia (cluster headache, paroxysmal hemicrania, SUNCT, SUNA, or hemicrania continua) according to ICHD-3 criteria.
  • Ability to provide written informed consent.
  • Availability for longitudinal follow-up and data collection.

Exclusion criteria

  • Secondary headache disorders.
  • Uncertain or unconfirmed diagnosis of a trigeminal autonomic cephalalgia.
  • Severe cognitive impairment or psychiatric condition interfering with reliable data collection.
  • Any condition that, in the investigator's judgment, may compromise participation or follow-up.

Treatment and study plan

Primary outcomes

  1. Baseline and routine follow-up visits through 3 years after enrollment

    Time frame: 3 years

    Number of headache attacks occurring during a 7-day period, assessed from headache diary data when available or from clinical history collected at study visits. Values will be recorded according to the participant's trigeminal autonomic cephalalgia subtype.

  2. Duration of individual headache attacks

    Time frame: 3 years

    Typical duration of headache attacks, expressed in minutes, assessed from headache diary data when available or from clinical history collected at study visits.

  3. Headache attack pain intensity assessed using the 11-point Numerical Rating Scale

    Time frame: 3 years

    Pain intensity will be rated on an 11-point Numerical Rating Scale from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores indicate greater pain intensity.

  4. Number of participants with cranial autonomic symptoms

    Time frame: 3 years

    Number and percentage of participants reporting cranial autonomic symptoms associated with headache attacks. Symptom categories collected include lacrimation, conjunctival injection, nasal congestion, ptosis, and miosis.

  5. Number of participants with premonitory symptoms

    Time frame: 3 years

    Number and percentage of participants reporting one or more premonitory symptoms associated with their trigeminal autonomic cephalalgia.

  6. Number of participants with postdromal symptoms

    Time frame: 3 years

    Number and percentage of participants reporting one or more postdromal symptoms associated with their trigeminal autonomic cephalalgia.

  7. Number of participants with a circadian attack pattern

    Time frame: 3 years

    Number and percentage of participants reporting a recurrent within-day temporal pattern in the occurrence of headache attacks.

  8. Number of participants with a circannual attack pattern

    Time frame: 3 years

    Number and percentage of participants reporting a recurrent seasonal or annual temporal pattern in the occurrence of headache attacks.

  9. Number of participants by disease-course category

    Time frame: 3 years

    Number and percentage of participants classified according to the applicable trigeminal autonomic cephalalgia disease-course category, including episodic and chronic forms where applicable.

  10. Number of participants with a transition in disease-course category

    Time frame: 3 years

    Number and percentage of participants who transition between applicable disease-course categories, including transitions between episodic and chronic forms where applicable.

  11. Number of participants receiving each acute treatment

    Time frame: 3 years

    Number and percentage of participants receiving each type of acute treatment for trigeminal autonomic cephalalgia in routine clinical practice.

  12. Number of participants receiving each preventive treatment

    Time frame: 3 years

    Number and percentage of participants receiving each type of preventive treatment for trigeminal autonomic cephalalgia in routine clinical practice.

  13. Number of participants initiating a new preventive treatment

    Time frame: 3 years

    Number and percentage of participants who initiate a new preventive treatment during follow-up.

  14. Number of participants switching preventive treatment

    Time frame: 3 years

    Number and percentage of participants who switch from one preventive treatment to another during follow-up.

  15. Number of participants discontinuing preventive treatment

    Time frame: 3 years

    Number and percentage of participants who discontinue a preventive treatment during follow-up. Reasons for discontinuation will be categorized where available.

  16. Duration of preventive treatment retention

    Time frame: 3 years

    Time from initiation of a preventive treatment to permanent discontinuation of that treatment, expressed in months.

Secondary outcomes

  1. Change from baseline in weekly attack frequency during preventive treatment

    Time frame: 3 years

    Change in the number of headache attacks per week from the pretreatment baseline value during preventive treatment.

  2. Number of participants achieving at least a 50% reduction in weekly attack frequency

    Time frame: 3 years

    Number and percentage of participants with a reduction of at least 50% in weekly attack frequency compared with the pretreatment baseline value.

  3. Change from baseline in days per week requiring acute headache medication

    Time frame: 3 years

    Change in the number of days per week on which acute headache medication is used compared with the pretreatment baseline value.

  4. Number of participants achieving sustained attack remission

    Time frame: 3 years

    Number and percentage of participants experiencing at least 3 consecutive months without headache attacks.

  5. Number of participants experiencing adverse events during preventive treatment

    Time frame: 3 years

    Number and percentage of participants with one or more adverse events occurring during exposure to preventive treatment. Adverse-event type and frequency will be summarized by treatment where available.

  6. Number of participants experiencing serious adverse events during preventive treatment

    Time frame: 3 years

    Number and percentage of participants with one or more serious adverse events occurring during exposure to preventive treatment.

  7. Number of participants discontinuing preventive treatment because of adverse events

    Time frame: 3 years

    Number and percentage of participants who permanently discontinue a preventive treatment because of an adverse event.

  8. Number of participants achieving pain freedom 15 minutes after acute treatment of the first treated attack

    Time frame: 3 years

    Number and percentage of participants with absence of headache pain 15 minutes after administration of acute treatment for the first prospectively assessed treated attack.

  9. Proportion of consecutively treated attacks with pain freedom 15 minutes after acute treatment

    Time frame: 3 years

    Proportion of up to four consecutive treated attacks in which pain freedom is achieved 15 minutes after administration of acute treatment.

  10. Number of participants achieving pain relief 15 minutes after acute treatment

    Time frame: 3 years

    Number and percentage of participants meeting the study definition of pain relief 15 minutes after administration of acute treatment.

  11. Number of participants achieving pain relief 2 hours after acute treatment

    Time frame: 3 years

    Number and percentage of participants meeting the study definition of pain relief 2 hours after administration of acute treatment.

  12. Functional Disability Scale score 15 minutes after acute treatment

    Time frame: 3 years

    Functional status 15 minutes after administration of acute treatment, assessed using the Functional Disability Scale specified in the study.

  13. Functional Disability Scale score 2 hours after acute treatment

    Time frame: 3 years

    Functional status 2 hours after administration of acute treatment, assessed using the Functional Disability Scale specified in the study.

  14. Number of participants with headache recurrence within 12 hours after initial pain freedom

    Time frame: 3 years

    Among participants who achieve initial pain freedom after acute treatment, number and percentage with recurrence of headache within 12 hours.

  15. Number of participants experiencing adverse events following acute treatment

    Time frame: 3 years

    Number and percentage of participants with one or more adverse events occurring in association with acute treatment.

  16. Number of participants experiencing serious adverse events following acute treatment

    Time frame: 3 years

    Number and percentage of participants with one or more serious adverse events occurring in association with acute treatment.

  17. Number of participants discontinuing an acute treatment because of adverse events

    Time frame: 3 years

    Number and percentage of participants who discontinue use of an acute treatment because of an adverse event.

  18. PGIC score

    Time frame: 3 years

    Patients impression of change after treatment initiation

  19. Change from baseline in ASC-12 score

    Time frame: 3 years

  20. Change from baseline in EQ-5D measure

    Time frame: 3 years

  21. Change from baseline in SF-36 score

    Time frame: 3 years

  22. Change from baseline in CHIQ score

    Time frame: 3 years

  23. Change from baseline in HARS score

    Time frame: 3 years

  24. Change from baseline in HDRS score

    Time frame: 3 years

  25. Change from baseline in HADS score

    Time frame: 3 years

  26. Change from baseline in modified LDQ score

    Time frame: 3 years

  27. Change from baseline in PSQI score

    Time frame: 3 years

Study contacts

Contact information is provided by the study sponsor or research team.

Danilo A Montisano, MD

CONTACT

[email protected]

02.2394

Licia Grazzi, MD

CONTACT

[email protected]

+ 02 2394

Sponsors and collaborators

Lead sponsor

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Other

Collaborators

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Pavia IRCCS Mondino di Pavia
  • University of Modena and Reggio Emilia
  • University of Roma La Sapienza
  • Università degli Studi dell'Aquila

Registry information

Official study title

Italian Trigeminal Autonomic Cephalalgias Assessment Study (ITACA)

Acronym: ITACA

Important dates

Study start
2026
Primary completion
2029
Study completion
2032
First posted
Sep 10, 2026
Registry last updated
Sep 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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