GAIN Symptoms: Post-traumatic Headache

NCT05857761 | Active Not Recruiting DMC

• 1 other identifier: GAIN: Post-traumatic Headache
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The overall aim of the study is to advance the knowledge on the characterization and underlying pathophysiological mechanisms of persistent post-traumatic headache (PTH) with a direct impact on the ability to diagnose and manage PTH effectively. The investigators also aim to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS), a novel intervention on PTH.

Conditions

Post-Traumatic Headache; Concussion, Mild; MTBI - Mild Traumatic Brain Injury

Keywords

Post-traumatic headache; Concussion; Mild Traumatic Brain Injury

Outcome Measures

Primary Outcomes (4)

• Change in the number of headache days of moderate to severe intensity

  Change in the number of headache days of moderate to severe intensity from baseline to 1-month post intervention based on a self-reported daily headache diary, a self-reported headache questionaire and Headache Impact test (HIT-6).

  Prior to intervention compared to 1 month after end of treatment.

• Changes in the concentration of biomarkers

  Changes in the blood biomarkers (such as neurofilament light chain, calcitonin gene related peptide, pituitary adenylate cyclase-activating polypeptide, cytokines, mRNA, microRNA and circular RNA) and somatosensory function from baseline to immediately after the completion of intervention (rTMS) and 1 month post-rTMS. Associations between total symptomload (Total RPQ score) and blood biomarker concentrations will be investigated.

  Prior to rTMS intervention, immediately after rTMS intervention and 1 month after end of treatment

• A comparison at baseline of the blood biomarker concentrations in the mTBI patients compared to healthy controls

  Differences in the blood biomarkers (such as neurofilament light chain, calcitonin gene related peptide, pituitary adenylate cyclase-activating polypeptide, cytokines, mRNA, microRNA and circular RNA) at baseline.

  Prior to rTMS intervention

• Characterization of PTH headache phenotypes using a self-constructed headache questionaire.

  Characterization of PTH headache phenotypes into e.g. migraine-like or tension-type like using a self-constructed headache questionnaire.

  3 months after mTBI

Secondary Outcomes (15)

• Change in the number of headache days of moderate to severe intensity

  Prior to intervention compared to 3 months after end of treatment.

• Change in severity of post-concussion symptoms covering physical, cognitive, and emotional symptoms.

  Prior to intervention compared to 1 and 3 months after end of treatment

• Change in the use of medication, non-pharmacological treatment and management strategies.

  Prior to intervention compared to 1 and 3 months after end of treatment

• Change in health-related quality of life

  Prior to intervention compared to 1 and 3 months after end of treatment

• Change in self-reported impact on participation and autonomy

  Prior to intervention compared to 1 and 3 months after end of treatment.

Study Arms (2)

Sham group

SHAM COMPARATOR

participants (n=31) will receive sham rTMS.

Device: Sham repetitive transcranial magnetic stimulation (rTMS)

Active rTMS treatment

ACTIVE COMPARATOR

Participants (n=31) will receive active rTMS treatment.

Device: Active repetitive transcranial magnetic stimulation (rTMS)

Interventions

Active repetitive transcranial magnetic stimulation (rTMS) DEVICE

Five sessions of active rTMS therapy will be distributed over 2 weeks (20 Hz, 2000 pulses, 90% resting motor threshold) will be delivered to left dorsolateral pre-frontal cortex (DLPFC) around 6 months post-trauma.

Active rTMS treatment

Sham repetitive transcranial magnetic stimulation (rTMS) DEVICE

Five sessions of sham rTMS therapy will be distributed over 2 weeks

Sham group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• mTBI within the last 2 to 4 months according to the diagnostic criteria recommended by the WHO task force
• age ≥ 18 years at the time of mTBI
• Rivermead Post-Concussion Symptoms Questionnaire (RPQ) score ≥ 3 (moderate or severe problem) for subitem headache and a diagnosis of persistent PTH attributed to mTBI according to ICHD-3.
• Additionally, for study 2 and 3, subjects have to be stable on preventative headache medication. However, subjects are permitted to take ''as needed'' (PRN) medications throughout the study with documentation in a daily headache diary.

You may not qualify if:

• objective neurological findings and/or acute trauma CT scan indicating neurological disease or brain damage
• previous mTBI within the last 2 years years leading to PCS lasting ≥ 3 months. Additionally, for study 2 and 3,
• Pre-trauma headache frequency ≥ 10 days in average per month the last 3 months prior to mTBI.
• past history of TMS therapy or TMS-related contraindications (pacemaker, epilepsy etc.).

Sponsors & Collaborators

• Central Denmark Region: collaborator
• University of Aarhus: lead
• Hammel Neurorehabilitation Centre and University Research Clinic: collaborator

Study Sites (1)

Reseach Unit Hammel Neurocenter

Hammel, 8450, Denmark

Location

Related Publications (2)

• Ebener M, Hasselhorn HM. Validation of Short Measures of Work Ability for Research and Employee Surveys. Int J Environ Res Public Health. 2019 Sep 12;16(18):3386. doi: 10.3390/ijerph16183386.

  PMID: 31547466 BACKGROUND

• Mollica A, Safavifar F, Fralick M, Giacobbe P, Lipsman N, Burke MJ. Transcranial Magnetic Stimulation for the Treatment of Concussion: A Systematic Review. Neuromodulation. 2021 Jul;24(5):803-812. doi: 10.1111/ner.13319. Epub 2020 Nov 12.

  PMID: 33184973 BACKGROUND

MeSH Terms

Conditions

Post-Traumatic Headache; Brain Concussion

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Injuries, Traumatic; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Study Officials

• Jørgen Feldbæk Nielsen, Proffessor

  Research Unit Hammel Neurocenter

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: A computer will randomize participants to either participate in the active- or the sham group. At end of treatment participants will be asked to answer if they have received sham- or active treatment in order to assess the success of participant-blinding.
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, PhD student

Model Details: The intervention study will be conducted as a randomized, sham-controlled, parallel group clinical trial consisting of an active (n=31) and a sham group (n=31).

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: May 15, 2023
• Study Start: August 28, 2023
• Primary Completion: August 31, 2024
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)