PERSONOLOGICAL STRUCTURE, COGNITIVE FUNCTIONS AND CENTRAL SENSITIZATION IN HEADACHE (AURA)

December 5, 2025 updated by: Anna Anselmo, IRCCS Centro Neurolesi Bonino Pulejo

Personological Structure, Cognitive Functions and Central Sensitization in Headache: Obstacles and Resources in the Treatment of Chronic and Episodic Headache.

Headache, in its episodic and chronic forms, cannot be considered solely as an isolated neurological symptom, but as a complex condition of a bio-psycho-social nature. While in the episodic form the painful episodes occur intermittently and have a variable impact on daily life, in the chronic form the disease evolves towards persistent pain, with more significant consequences on personal, social and work functioning. The following study protocol aims to investigate in an integrated manner the neurological, cognitive and psychological mechanisms involved in headache, with particular attention to the differences between episodic and chronic forms. The main objective is to assess the neuropsychological profiles and pain response of patients, monitoring their evolution over a period of approximately six months, considering the impact of central sensitisation, personality structure and any psychopathological comorbidities on pain management and treatment adherence. The protocol adopts a multidimensional approach aimed at optimising therapeutic efficacy and improving patients' quality of life, preventing progression to chronicity.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an observational, prospective study with two assessment timepoints: baseline (T0) and follow-up at approximately six months (T1). The overall duration of the project is estimated at about three years, including enrollment of all planned participants, completion of follow-up, data analysis and dissemination of results.

The study is conducted at the IRCCS Centro Neurolesi "Bonino-Pulejo" with UTIC P.O. "Piemonte" in Messina, Italy, within the Headache Outpatient Clinic.

The target population consists of adult patients with a diagnosis of chronic or episodic headache referring to the Headache Outpatient Clinic. Sample size was calculated using G*Power 3.1, taking as reference the primary objective of comparing the evolution (baseline vs T1) of main clinical-neuropsychological outcomes between chronic and episodic headache groups. The primary test was modeled as a repeated-measures ANOVA on the group×time interaction (two groups, two measurements), analogous to the interaction component of a linear mixed model.

With a significance level α = 0.05, statistical power 1-β = 0.90, intra-subject correlation r = 0.60 and two measurements, assuming an interaction effect size f = 0.20 and nonsphericity correction ε = 1, the minimum required sample size is N = 56 subjects (28 per group). Taking into account an expected dropout rate of 15%, the required enrollment was increased to N = 64 participants (32 per group), in order to preserve the planned power for the primary analysis.

Inclusion criteria

  • Age between 18 and 60 years;
  • Diagnosis of chronic or episodic headache;
  • Patients attending the Headache Outpatient Clinic. Exclusion criteria
  • Presence of severe psychiatric and neurological disorders;
  • Presence of oncological diseases in terminal stage Identification and numbering of subjects In accordance with Good Clinical Practice (GCP), each subject is identified by an unequivocal numerical code that serves as the subject's identifier throughout the study. In this protocol, the code consists of a three-digit subject number assigned in progressive order starting from 001 when the subject signs the informed consent form. The investigator records the subject's name and corresponding code in a dedicated dataset accessible only to authorized study collaborators, thereby ensuring traceability and confidentiality.

Study procedures All potentially eligible subjects are informed about the aims and procedures of the study and are free to choose whether to participate. Only after the subject, or his/her legal representative, has agreed to participate and has signed the informed consent form, do the investigators proceed with the planned activities.

Clinical data for each subject are stored in a secure database accessible to study collaborators via personal credentials. After verifying the inclusion and exclusion criteria and obtaining informed consent, patients are formally enrolled and scheduled for the baseline assessment (T0).

Baseline visit (T0)

At T0, the following procedures are performed:

  • Verification of inclusion and exclusion criteria
  • Collection of demographic data
  • Collection of clinical history, including headache characteristics, comorbidities and medication use

After the clinical assessment, a standardized battery of tests is administered to evaluate dimensions related to chronic pain and quality of life:

  • Cognitive functions: Brief Cognitive Status Exam (BCSE) and/or Montreal Cognitive Assessment (MoCA)
  • Pain intensity and central sensitization: Numeric Pain Rating Scale (NPRS) and Central Sensitization Inventory (CSI)
  • Personality: Minnesota Multiphasic Personality Inventory 3 (MMPI-3)
  • Treatment engagement and adherence: Patient Health Engagement Scale (PHE-S) and Morisky Medication Adherence Scale (MMAS)
  • Psychological distress: Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI)
  • Digital habits: ad-hoc questionnaire on digital behaviors in patients with headache

Follow-up visit (T1) At approximately six months (T1), patients return for follow-up. All standardized instruments administered at T0 are readministered in order to evaluate changes over time in cognitive functioning, pain intensity and sensitization, personality and psychopathological dimensions, treatment adherence and digital habits.

Study Type

Observational

Enrollment (Estimated)

64

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Sicily
      • Messina, Sicily, Italy, 98066
        • Recruiting
        • IRCCS Centro Neurolesi Bonino Pulejo
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The target population consists of adult patients with a diagnosis of chronic or episodic headache referring to the Headache Outpatient Clinic. Sample size was calculated using G*Power 3.1, taking as reference the primary objective of comparing the evolution (baseline vs T1) of main clinical-neuropsychological outcomes between chronic and episodic headache groups. The primary test was modeled as a repeated-measures ANOVA on the group×time interaction (two groups, two measurements), analogous to the interaction component of a linear mixed model.

With a significance level α = 0.05, statistical power 1-β = 0.90, intra-subject correlation r = 0.60 and two measurements, assuming an interaction effect size f = 0.20 and nonsphericity correction ε = 1, the minimum required sample size is N = 56 subjects (28 per group). Taking into account an expected dropout rate of 15%, the required enrollment was increased to N = 64 participants (32 per group), in order to preserve the planned power for the p

Description

Inclusion Criteria:

  • Age between 18 and 60 years;
  • Diagnosis of chronic or episodic headache;
  • Patients attending the Headache Outpatient Clinic.

Exclusion Criteria:

  • Presence of severe psychiatric and neurological disorders;
  • Presence of oncological diseases in terminal stage

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Chronic headache
Patients suffering from chronic headache
Other: Neuropsychological assessment
Standardized and ad hoc test battery for comprehensive neuropsychological assessment
Episodic headache
Patients suffering from episodic headache
Other: Neuropsychological assessment
Standardized and ad hoc test battery for comprehensive neuropsychological assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuropsychological assessment
Time Frame: 6 months
•Cognitive functions: Brief Cognitive Status Exam (BCSE) and/or Montreal Cognitive Assessment (MoCA)
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central sensitization
Time Frame: 6 months
Central Sensitization Inventory (CSI)
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Centro Neurolesi Bonino Pulejo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 20, 2025

Primary Completion (Estimated)

November 20, 2028

Study Completion (Estimated)

November 20, 2028

Study Registration Dates

First Submitted

November 24, 2025

First Submitted That Met QC Criteria

December 5, 2025

First Posted (Actual)

December 8, 2025

Study Record Updates

Last Update Posted (Actual)

December 8, 2025

Last Update Submitted That Met QC Criteria

December 5, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEL/U117/25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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