Cluster Headache, Hemicrania Continua, Paroxysmal Hemicrania, Short Lasting Unilateral Neuralgiform Headache Attacks, SUNCT, Trigeminal Autonomic Cephalalgias
Conditions
Keywords
trigeminal autonomic cephalalgias, TACs, cluster headache, paroxysmal hemicrania, SUNCT, SUNA, hemicrania continua, real-world data
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
University of Modena and Reggio Emilia
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Università degli Studi dell'Aquila
University of Roma La Sapienza
Pavia IRCCS Mondino di Pavia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline and routine follow-up visits through 3 years after enrollment | 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. |
| Duration of individual headache attacks | 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. |
| Headache attack pain intensity assessed using the 11-point Numerical Rating Scale | 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. |
| Number of participants with cranial autonomic symptoms | 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. |
| Number of participants with premonitory symptoms | 3 years | Number and percentage of participants reporting one or more premonitory symptoms associated with their trigeminal autonomic cephalalgia. |
| Number of participants with postdromal symptoms | 3 years | Number and percentage of participants reporting one or more postdromal symptoms associated with their trigeminal autonomic cephalalgia. |
| Number of participants with a circadian attack pattern | 3 years | Number and percentage of participants reporting a recurrent within-day temporal pattern in the occurrence of headache attacks. |
| Number of participants with a circannual attack pattern | 3 years | Number and percentage of participants reporting a recurrent seasonal or annual temporal pattern in the occurrence of headache attacks. |
| Number of participants by disease-course category | 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. |
| Number of participants with a transition in disease-course category | 3 years | Number and percentage of participants who transition between applicable disease-course categories, including transitions between episodic and chronic forms where applicable. |
| Number of participants receiving each acute treatment | 3 years | Number and percentage of participants receiving each type of acute treatment for trigeminal autonomic cephalalgia in routine clinical practice. |
| Number of participants receiving each preventive treatment | 3 years | Number and percentage of participants receiving each type of preventive treatment for trigeminal autonomic cephalalgia in routine clinical practice. |
| Number of participants initiating a new preventive treatment | 3 years | Number and percentage of participants who initiate a new preventive treatment during follow-up. |
| Number of participants switching preventive treatment | 3 years | Number and percentage of participants who switch from one preventive treatment to another during follow-up. |
| Number of participants discontinuing preventive treatment | 3 years | Number and percentage of participants who discontinue a preventive treatment during follow-up. Reasons for discontinuation will be categorized where available. |
| Duration of preventive treatment retention | 3 years | Time from initiation of a preventive treatment to permanent discontinuation of that treatment, expressed in months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in weekly attack frequency during preventive treatment | 3 years | Change in the number of headache attacks per week from the pretreatment baseline value during preventive treatment. |
| Number of participants achieving at least a 50% reduction in weekly attack frequency | 3 years | Number and percentage of participants with a reduction of at least 50% in weekly attack frequency compared with the pretreatment baseline value. |
| Change from baseline in days per week requiring acute headache medication | 3 years | Change in the number of days per week on which acute headache medication is used compared with the pretreatment baseline value. |
| Number of participants achieving sustained attack remission | 3 years | Number and percentage of participants experiencing at least 3 consecutive months without headache attacks. |
| Number of participants experiencing adverse events during preventive treatment | 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. |
| Number of participants experiencing serious adverse events during preventive treatment | 3 years | Number and percentage of participants with one or more serious adverse events occurring during exposure to preventive treatment. |
| Number of participants discontinuing preventive treatment because of adverse events | 3 years | Number and percentage of participants who permanently discontinue a preventive treatment because of an adverse event. |
| Number of participants achieving pain freedom 15 minutes after acute treatment of the first treated attack | 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. |
| Proportion of consecutively treated attacks with pain freedom 15 minutes after acute treatment | 3 years | Proportion of up to four consecutive treated attacks in which pain freedom is achieved 15 minutes after administration of acute treatment. |
| Number of participants achieving pain relief 15 minutes after acute treatment | 3 years | Number and percentage of participants meeting the study definition of pain relief 15 minutes after administration of acute treatment. |
| Number of participants achieving pain relief 2 hours after acute treatment | 3 years | Number and percentage of participants meeting the study definition of pain relief 2 hours after administration of acute treatment. |
| Functional Disability Scale score 15 minutes after acute treatment | 3 years | Functional status 15 minutes after administration of acute treatment, assessed using the Functional Disability Scale specified in the study. |
| Functional Disability Scale score 2 hours after acute treatment | 3 years | Functional status 2 hours after administration of acute treatment, assessed using the Functional Disability Scale specified in the study. |
| Number of participants with headache recurrence within 12 hours after initial pain freedom | 3 years | Among participants who achieve initial pain freedom after acute treatment, number and percentage with recurrence of headache within 12 hours. |
| Number of participants experiencing adverse events following acute treatment | 3 years | Number and percentage of participants with one or more adverse events occurring in association with acute treatment. |
| Number of participants experiencing serious adverse events following acute treatment | 3 years | Number and percentage of participants with one or more serious adverse events occurring in association with acute treatment. |
| Number of participants discontinuing an acute treatment because of adverse events | 3 years | Number and percentage of participants who discontinue use of an acute treatment because of an adverse event. |
| PGIC score | 3 years | Patients impression of change after treatment initiation |
| Change from baseline in ASC-12 score | 3 years | — |
| Change from baseline in EQ-5D measure | 3 years | — |
| Change from baseline in SF-36 score | 3 years | — |
| Change from baseline in CHIQ score | 3 years | — |
| Change from baseline in HARS score | 3 years | — |
| Change from baseline in HDRS score | 3 years | — |
| Change from baseline in HADS score | 3 years | — |
| Change from baseline in modified LDQ score | 3 years | — |
| Change from baseline in PSQI score | 3 years | — |
Countries
Italy
Contacts
CONTACTLicia Grazzi, MD
CONTACTDanilo A Montisano, MD
PRINCIPAL_INVESTIGATORLicia Grazzi, MD
Fondazione IRCCS Istituto Neurologico C. Besta
Outcome results
None listed