An observational study in Trigeminal Autonomic Cephalalgias, Cluster Headache and Paroxysmal Hemicrania, sponsored by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-22.
Sponsored by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta · Observational
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.
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.
123 studies on the registry are indexed under Cluster Headache; 26 are open to participants now.
This study's planned enrollment of 800 is above the median of 68 across 32 observational studies indexed under Cluster Headache.
Browse Cluster Headache studies →Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta is the lead sponsor of 84 studies on the registry; 32 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adult outpatients with an ICHD-3 diagnosis of trigeminal autonomic cephalalgia (cluster headache, paroxysmal hemicrania, SUNCT, SUNA, or hemicrania continua) evaluated at specialized headache centers participating in the study.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Baseline and routine follow-up visits through 3 years after enrollment
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.
Time frame: 3 years
Duration of individual headache attacks
Typical duration of headache attacks, expressed in minutes, assessed from headache diary data when available or from clinical history collected at study visits.
Time frame: 3 years
Headache attack pain intensity assessed using the 11-point Numerical Rating Scale
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.
Time frame: 3 years
Number of participants with cranial autonomic symptoms
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.
Time frame: 3 years
Number of participants with premonitory symptoms
Number and percentage of participants reporting one or more premonitory symptoms associated with their trigeminal autonomic cephalalgia.
Time frame: 3 years
Number of participants with postdromal symptoms
Number and percentage of participants reporting one or more postdromal symptoms associated with their trigeminal autonomic cephalalgia.
Time frame: 3 years
Number of participants with a circadian attack pattern
Number and percentage of participants reporting a recurrent within-day temporal pattern in the occurrence of headache attacks.
Time frame: 3 years
Number of participants with a circannual attack pattern
Number and percentage of participants reporting a recurrent seasonal or annual temporal pattern in the occurrence of headache attacks.
Time frame: 3 years
Number of participants by disease-course category
Number and percentage of participants classified according to the applicable trigeminal autonomic cephalalgia disease-course category, including episodic and chronic forms where applicable.
Time frame: 3 years
Number of participants with a transition in disease-course category
Number and percentage of participants who transition between applicable disease-course categories, including transitions between episodic and chronic forms where applicable.
Time frame: 3 years
Number of participants receiving each acute treatment
Number and percentage of participants receiving each type of acute treatment for trigeminal autonomic cephalalgia in routine clinical practice.
Time frame: 3 years
Number of participants receiving each preventive treatment
Number and percentage of participants receiving each type of preventive treatment for trigeminal autonomic cephalalgia in routine clinical practice.
Time frame: 3 years
Number of participants initiating a new preventive treatment
Number and percentage of participants who initiate a new preventive treatment during follow-up.
Time frame: 3 years
Number of participants switching preventive treatment
Number and percentage of participants who switch from one preventive treatment to another during follow-up.
Time frame: 3 years
Number of participants discontinuing preventive treatment
Number and percentage of participants who discontinue a preventive treatment during follow-up. Reasons for discontinuation will be categorized where available.
Time frame: 3 years
Duration of preventive treatment retention
Time from initiation of a preventive treatment to permanent discontinuation of that treatment, expressed in months.
Time frame: 3 years
Change from baseline in weekly attack frequency during preventive treatment
Change in the number of headache attacks per week from the pretreatment baseline value during preventive treatment.
Time frame: 3 years
Number of participants achieving at least a 50% reduction in weekly attack frequency
Number and percentage of participants with a reduction of at least 50% in weekly attack frequency compared with the pretreatment baseline value.
Time frame: 3 years
Change from baseline in days per week requiring acute headache medication
Change in the number of days per week on which acute headache medication is used compared with the pretreatment baseline value.
Time frame: 3 years
Number of participants achieving sustained attack remission
Number and percentage of participants experiencing at least 3 consecutive months without headache attacks.
Time frame: 3 years
Number of participants experiencing adverse events during preventive treatment
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.
Time frame: 3 years
Number of participants experiencing serious adverse events during preventive treatment
Number and percentage of participants with one or more serious adverse events occurring during exposure to preventive treatment.
Time frame: 3 years
Number of participants discontinuing preventive treatment because of adverse events
Number and percentage of participants who permanently discontinue a preventive treatment because of an adverse event.
Time frame: 3 years
Number of participants achieving pain freedom 15 minutes after acute treatment of the first treated attack
Number and percentage of participants with absence of headache pain 15 minutes after administration of acute treatment for the first prospectively assessed treated attack.
Time frame: 3 years
Proportion of consecutively treated attacks with pain freedom 15 minutes after acute treatment
Proportion of up to four consecutive treated attacks in which pain freedom is achieved 15 minutes after administration of acute treatment.
Time frame: 3 years
Number of participants achieving pain relief 15 minutes after acute treatment
Number and percentage of participants meeting the study definition of pain relief 15 minutes after administration of acute treatment.
Time frame: 3 years
Number of participants achieving pain relief 2 hours after acute treatment
Number and percentage of participants meeting the study definition of pain relief 2 hours after administration of acute treatment.
Time frame: 3 years
Functional Disability Scale score 15 minutes after acute treatment
Functional status 15 minutes after administration of acute treatment, assessed using the Functional Disability Scale specified in the study.
Time frame: 3 years
Functional Disability Scale score 2 hours after acute treatment
Functional status 2 hours after administration of acute treatment, assessed using the Functional Disability Scale specified in the study.
Time frame: 3 years
Number of participants with headache recurrence within 12 hours after initial pain freedom
Among participants who achieve initial pain freedom after acute treatment, number and percentage with recurrence of headache within 12 hours.
Time frame: 3 years
Number of participants experiencing adverse events following acute treatment
Number and percentage of participants with one or more adverse events occurring in association with acute treatment.
Time frame: 3 years
Number of participants experiencing serious adverse events following acute treatment
Number and percentage of participants with one or more serious adverse events occurring in association with acute treatment.
Time frame: 3 years
Number of participants discontinuing an acute treatment because of adverse events
Number and percentage of participants who discontinue use of an acute treatment because of an adverse event.
Time frame: 3 years
PGIC score
Patients impression of change after treatment initiation
Time frame: 3 years
Change from baseline in ASC-12 score
Time frame: 3 years
Change from baseline in EQ-5D measure
Time frame: 3 years
Change from baseline in SF-36 score
Time frame: 3 years
Change from baseline in CHIQ score
Time frame: 3 years
Change from baseline in HARS score
Time frame: 3 years
Change from baseline in HDRS score
Time frame: 3 years
Change from baseline in HADS score
Time frame: 3 years
Change from baseline in modified LDQ score
Time frame: 3 years
Change from baseline in PSQI score
Time frame: 3 years
Plan to share: No
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta