Clinical Features and Current Treatment of Primary Headache

Not yet recruiting

• Conditions: Primary Headache

• Registration Number: NCT06883955
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

This study is a prospective, observational cohort study. The plan of this study is to consecutively enroll 2,000 primary headache patients who meet the inclusion criteria from the neurology outpatient department and inpatient department of Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Basic clinical data registration, various scale evaluations, cranial imaging examinations, and collection of blood and fecal biological samples will be completed. During the 10-year follow-up plan, systematic clinical evaluations of the disease severity, diagnosis and treatment, living ability and health status of patients will be carried out regularly every 6 - 12 months. Imaging and other functional evaluations will be conducted when necessary. Data collection includes:

Demographic data (including age, gender, education, ethnicity, marital status, occupation, etc.); General clinical data (past medical history, medication history, personal history, menstrual and childbearing history, family history, etc.); Clinical data of primary headache: headache frequency, duration, severity (Numeric Rating Scale for pain, NRS), headache-related medication use, drug efficacy and side effects; Scale evaluations: MIDAS, HIT-6, BPI, MSQ, ADL, CDR, PGIC, CGIC, PHQ-4, mTOQ-4, ASC-12, MIBS-4, HARDSHIP, WHO-QOL BREF, HAMD, HAMA, TNQ; Records of neurological imaging examinations, blood sample and fecal sample collection.

Detailed Description

Background Headache is one of the most common diseases in the nervous system. Approximately 52% of adults worldwide suffer from primary headache. The third edition of the International Classification of Headache Disorders in 2018 classified primary headache into migraine, tension-type headache, trigeminal autonomic cephalalgia, and other primary headaches. Although primary headache has no obvious organic lesions, it can lead to transient or permanent central nervous system dysfunction, affecting people's daily life and work, and imposing a huge economic burden on society. This study intends to establish a prospective cohort of patients with primary headache, observe the relevant risk factors, clinical treatment efficacy, and prognosis of patients with primary headache, and explore the relevant clinical factors and biomarkers for a favorable prognosis. During the 10-year follow-up plan, systematic clinical evaluations will be regularly carried out on the disease severity, diagnosis and treatment status, living ability, and health status of patients. When necessary, blood and fecal samples will be collected and imaging evaluations will be conducted to complete the construction of a clinical diagnosis and treatment information database for patients with primary headache, and analyze the clinical factors related to the prognosis.

Research Objectives To observe the risk factors, clinical characteristics, treatment regimens and their efficacy, and prognosis of patients with primary headache, and to explore the relevant clinical factors and biomarkers for a favorable prognosis.

Research Design This study adopts a single-center, prospective cohort design.

Baseline Assessment Demographic data (including: age, gender, education level, ethnicity, marital status, occupation, etc.); General clinical data (past medical history, medication history, personal history, menstrual, marital and childbearing history, and family history, etc.); Clinical data of primary headache: headache frequency, duration, severity (Numerical Rating Scale for Pain, NRS), past headache-related medication use, medication efficacy and side effects; Scale Evaluation: MIDAS, HIT-6, BPI, MSQ, ADL, CDR, PGIC, CGIC, PHQ-4, mTOQ-4, ASC-12, MIBS-4, HARDSHIP, WHO-QOL BREF, HAMD, HAMA, TNQ; Biochemical Indicators: White blood cell count and classification, inflammatory indicators in the blood; fecal bacteriological examination; Changes in Imaging Biomarkers: Changes in brain structure, brain function, and metabolism.

Follow-up Study

Within 6 months after enrollment, follow-up assessments will be conducted every 1-3 months; from half a year to 10 years after enrollment, follow-up assessments will be conducted every 6-12 months (the assessment methods include in-person interviews, telephone follow-ups, and online follow-ups). The following data will be collected:

Clinical data of primary headache: headache frequency, duration, severity (Numerical Rating Scale for Pain, NRS), the use of headache-related medications (types, dosages, efficacy, and side effects); Scale Evaluation: MIDAS, HIT-6, BPI, MSQ, ADL, CDR, PGIC, CGIC, PHQ-4, mTOQ-4, ASC-12, MIBS-4, HARDSHIP, WHO-QOL BREF, HAMD, HAMA, TNQ; Blood and fecal tests and cranial imaging examinations (when clinically necessary and with the patient's/family member's consent and cooperation).

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-05
• Study Start: 2025-03-08
• Study First Submitted QC: 2025-03-13
• Last Update Submitted: 2025-03-13
• Study First Posted: 2025-03-19
• Last Update Posted: 2025-03-19
• Primary Completion: 2037-12-31
• Study Completion: 2037-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

1. Age is less than 65 years old.
2. Meets the diagnostic criteria for relevant primary headaches (such as tension-type headache, migraine, cluster headache, trigeminal autonomic cephalalgia, etc.) in the third edition of the International Classification of Headache Disorders (ICHD - 3).
3. Is willing and able to participate throughout the entire study period and sign the informed consent form.
4. Has the ability to complete the "Headache Diary" independently or with the help of a guardian.

Exclusion Criteria

1. Secondary headache
2. High - risk populations, such as those with severe heart disease, impaired liver and kidney function, malignant tumors, etc.
3. Patients with mental illness, cognitive impairment, or those who are unable to cooperate with the research requirements
4. History of intracranial lesions or other nervous system diseases (including stroke, epilepsy, etc.)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The number of headache days per month.	10 years	The number of headache days per month: This indicator is used to count the actual number of days each research subject experiences headache symptoms within each month. Through the recording and analysis of the number of headache days per month, it can directly reflect the frequency of headache attacks, helping researchers understand the duration of the interference of primary headache with the daily life of patients, and further evaluate the severity and development trend of the disease.
Changes in scores of headache assessment scales: NRS.	10 years	NRS (The Numerical Rating Scale for Pain) is a commonly used simple pain measurement tool. Patients select a value within the numerical range from 0 (representing no pain) to 10 (representing the most severe pain) according to the degree of pain they feel, to quantify the intensity of pain.
Changes in scores of headache assessment scales: HIT-6.	10 years	The HIT - 6 scale (the Headache Impact Test - 6) is mainly used to evaluate the impact of headache on various aspects of patients' lives, such as daily activities, social interaction, work, etc.

Secondary Outcome Measures

Name	Time	Method
The number of days of emergency medication use per month.	10 years
The types of preventive medications and the number of days of use per month.	10 years
Changes in scale scores at MIDAS.	10 years	Changes in scale scores at Migraine Disability Assessment Scale (MIDAS)
Changes in scale scores at BPI.	10 years	Changes in scale scores at Brief Pain Inventory (BPI).
Changes in scale scores at MSQ.	10 years	Changes in scale scores at Migraine Specific Quality of Life Questionnaire (MSQ).
Changes in scale scores at PGIC and CGIC.	10 years	Changes in scale scores at Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC).
Changes in scale scores at HAMD and HAMA.	10 years	Changes in scale scores at Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA).
Changes in scale scores at WHO - QOLBREF.	10 years	Changes in scale scores at World Health Organization Quality of Life - BREF (WHO - QOL BREF).
Changes in scale scores at HARDSHIP.	10 years	Changes in scale scores at Headache - Related Disability Scale (HARDSHIP).
Concentration of White Blood Cell Count and Subtypes in Peripheral Blood.	10 years	Absolute counts (×10\^9/L) and percentage (%) of neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
Change in serum inflammatory cytokine levels.	10 years	Concentration of pro-inflammatory cytokines (IL-6, TNF-α, CRP) in serum measured by chemiluminescence immunoassay.
Diversity and Abundance of Fecal Microbiota.	10 years	Shannon index (unitless), Firmicutes/Bacteroidetes ratio (%).
Change in gray matter volume.	10 years	Regional gray matter volume in pain-processing areas (insula, thalamus, anterior cingulate cortex) quantified by voxel-based morphometry (VBM) on 3T MRI.
Change in resting-state functional connectivity.	10 years	Functional connectivity strength within the default mode network (DMN) measured by fMRI BOLD signal.
Change in brain metabolic profile.	10 years	Concentration ratio of N-acetylaspartate (NAA) to creatine (Cr) in the thalamus measured by proton magnetic resonance spectroscopy.

Trial Locations

Locations (1)

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University; 🇨🇳 Guangzhou, Guangdong, China