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GAIN Symptoms: Post-traumatic Headache

Primary Purpose

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

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Active repetitive transcranial magnetic stimulation (rTMS)
Sham repetitive transcranial magnetic stimulation (rTMS)
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Post-Traumatic Headache focused on measuring Post-traumatic headache, Concussion, Mild Traumatic Brain Injury

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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.).

Sites / Locations

  • Reseach Unit Hammel NeurocenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Active Comparator

Arm Label

Sham group

Active rTMS treatment

Arm Description

participants (n=50) will receive sham rTMS.

Participants (n=50) will receive active rTMS treatment.

Outcomes

Primary Outcome Measures

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.
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).

Secondary Outcome Measures

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).
Change in severity of post-concussion symptoms covering physical, cognitive, and emotional symptoms.
Will be measured using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) [range 0-64 (worst)].
Change in the use of medication, non-pharmacological treatment and management strategies.
Will be measured using a self-constructed, self-reported questionaire
Change in health-related quality of life
Will be measured using the EuroQol-5 Domain (EQ-5D-5L) [5 items, range 0-100. 100 means the best health you can imagine]
Change in self-reported impact on participation and autonomy
Will be measured using the Impact on Participation and Autonomy questionaire (IPAQ-DK). IPAQ DK consists of 32 items which can be answered from 0-4. Higher score corresponds to less participation and autonomy.
Change in Psychological Distress
Will be measured using the Screening for Anxiety and depression (SCL-13). SCL-13 consists of 13 items from the Symptom Check List-90. Each item can be ranged from 0-4 (not at all- very much). A high score corresponds to a high level of depressive and/or anxiety symptoms.
Change in illness perception
Will be measured using the The Brief Illness Perception Questionnaire (B-IPQ). B-IPQ consists of 9 items. Each item is rated on a 0-10 scale, with higher scores indicating a more threatening perception of the illness. The total score is calculated by summing the scores of all eight items, with a possible range of 0-80. Higher scores indicate worse illness perception.
Change in Pain Catastrophizing
Will be measured using the Pain Catastrophizing Scale (PCS-DK). Consists of 13 items. Each item is ranged from 0-4. A high score corresponds to a high degree of pain catastrophizing.
Change in facial perception
Will be measured using a self-constructed, self-reported questionaire
Change in self-reported efficacy of treatment
Will be measured using Patients Global Impression of Change (PGIC-DK). 1 item ranged 0-6. A high score corresponds to a subjective improvement.
Change in how neck pain affects daily life
Will be measured using the Neck Pain Disability Index (NDI-DK). 8 items ranged 0-6. A high score corresponds to a high impact on daily life.
Changes in sleep quality
Will be measured using the Pittsburgh Sleep Quality Index (PSQI-DK). seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.
Changes in the somatosensory function.
Change in the somatosensory function from baseline to immediately after the completion of intervention (rTMS) and 1 month post-rTMS.
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.
Characterization of PTH headache phenotypes using the Headache Impact Scale.
Characterization of PTH headache phenotypes into e.g. migraine-like or tension-type like using the Headache Impact Scale (HIT-6). HIT-6 is a 6 item scale. Each item is ranged from 0-5 ("never-always"). A high total score corresponds to a high impact of the headache on daily functioning.
Changes in headache phenotype using a self-constructed headache questionaire.
Describing changes in the headache phenotype (e.g. migraine-like or tension-type like) longitudinally using a self-constructed headache questionnaire.
Changes in headache phenotype using the Headache Impact Scale .
Describing changes in the headache phenotype (e.g. migraine-like or tension-type like) longitudinally using the Headache Impact Scale (HIT-6). HIT-6 is a 6 item scale. Each item is ranged from 0-5 ("never-always"). A high total score corresponds to a high impact of the headache on daily functioning.

Full Information

First Posted
March 24, 2023
Last Updated
October 18, 2023
Sponsor
University of Aarhus
Collaborators
Hammel Neurorehabilitation Centre and University Research Clinic, Central Denmark Region
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1. Study Identification

Unique Protocol Identification Number
NCT05857761
Brief Title
GAIN Symptoms: Post-traumatic Headache
Official Title
Post-traumatic Headache: Phenotyping and Exploring Pathophysiological Insights and Novel Treatment Strategies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 28, 2023 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Aarhus
Collaborators
Hammel Neurorehabilitation Centre and University Research Clinic, Central Denmark Region

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
Post-traumatic headache (PTH) is one of the most common and persistent symptoms following mild traumatic brain injury (mTBI), with an estimation of 18-22% developing persistent (> 3 months) PTH. PTH is highly disabling. Unfortunately, its typical characteristics and pathophysiology are poorly understood leading to its complicated and diverse management. There is no agreement on the clinical presentation of PTH.This is largely due to the scarcity of longitudinal prospective data on large cohorts of PTH. Describing headache phenotypes longitudinally might improve disease characterization, facilitate better classification and provide evidence based-criteria of diagnosing PTH. Furthermore, exploring biomarkers associated with mTBI may provide new knowledge on the poorly understood pathophysiology of post commotional symptoms (PCS) and PTH. Additionally, there are indications of somatosensory disturbances and impaired endogenous analgesic systems in PTH patients. Assessment of somatosensory signs and symptoms in relation to pain complaints and functioning of endogenous analgesic system may also aid in better understanding of pain mechanisms in these patients. Functioning of endogenous analgesic system can be assessed using conditioned pain modulation (CPM) paradigms. Further, a curious observation in concussion patients with face and/or head pain is that they perceive painful/affected area (head and/or face region) as "swollen" or "different" without any clinical signs or obvious physical differences. Hence, such "illusions" represent body image distortions or perceptual distortion (PD) of the head or face region, and may contribute to the chronification of pain. PD can significantly affect psychosocial well-being of patients as the face/head region is a key feature of one´s identity. Unfortunately, such a distressing phenomenon has not been investigated before in these patients. Currently, no strong evidence-based treatment guidelines for PTH exist. Neuromodulation using repetitive transcranial magnetic stimulation (rTMS) targeting involved brain regions and functional networks has recently been employed to treat several chronic pain conditions including migraine. Thus, rTMS could offer an optimal new treatment strategy for PTH, as there is an evidence of brain network dysfunction in these patients. The overall aim is to advance the knowledge on the characterization and underlying pathophysiological mechanisms of persistent PTH. The aim is also to measure the prevalence of perceived size changes (PD) of head and/or face region in patients with mild traumatic brain injury and its association with pain/PTH and other post commotional symptoms (PCS). The investigators will also evaluate the efficacy of rTMS on PTH. Deep phenotyping of PTH will be performed. Blood samples from mTBI patients will be examined for the biomarkers of PCS and PTH and the association between the biomarkers and the symptom levels of PCS, in particular PTH frequency and intensity will be evaluated. Additionally, the association between somatosensory function including CPM and the PTH frequency and intensity will be examined. Further, the effect of rTMS on headache severity and frequency (primary outcome) and somatosensory function, PD and other PCS (secondary outcome) after 1 and 3 months of stimulation will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-Traumatic Headache, Concussion, Mild, MTBI - Mild Traumatic Brain Injury
Keywords
Post-traumatic headache, Concussion, Mild Traumatic Brain Injury

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The intervention study will be conducted as a randomized, sham-controlled, parallel group clinical trial consisting of an active (n=50) and a sham group (n=50).
Masking
Participant
Masking Description
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.
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sham group
Arm Type
Sham Comparator
Arm Description
participants (n=50) will receive sham rTMS.
Arm Title
Active rTMS treatment
Arm Type
Active Comparator
Arm Description
Participants (n=50) will receive active rTMS treatment.
Intervention Type
Device
Intervention Name(s)
Active repetitive transcranial magnetic stimulation (rTMS)
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham repetitive transcranial magnetic stimulation (rTMS)
Intervention Description
Five sessions of sham rTMS therapy will be distributed over 2 weeks
Primary Outcome Measure Information:
Title
Changes in the concentration of biomarkers
Description
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.
Time Frame
prior to rTMS intervention, immediately after rTMS intervention and 1 month after end of treatment
Title
Change in the number of headache days of moderate to severe intensity
Description
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).
Time Frame
Prior to intervention compared to 1 month after end of treatment.
Secondary Outcome Measure Information:
Title
Change in the number of headache days of moderate to severe intensity
Description
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).
Time Frame
Prior to intervention compared to 3 months after end of treatment.
Title
Change in severity of post-concussion symptoms covering physical, cognitive, and emotional symptoms.
Description
Will be measured using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) [range 0-64 (worst)].
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Change in the use of medication, non-pharmacological treatment and management strategies.
Description
Will be measured using a self-constructed, self-reported questionaire
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Change in health-related quality of life
Description
Will be measured using the EuroQol-5 Domain (EQ-5D-5L) [5 items, range 0-100. 100 means the best health you can imagine]
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Change in self-reported impact on participation and autonomy
Description
Will be measured using the Impact on Participation and Autonomy questionaire (IPAQ-DK). IPAQ DK consists of 32 items which can be answered from 0-4. Higher score corresponds to less participation and autonomy.
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment.
Title
Change in Psychological Distress
Description
Will be measured using the Screening for Anxiety and depression (SCL-13). SCL-13 consists of 13 items from the Symptom Check List-90. Each item can be ranged from 0-4 (not at all- very much). A high score corresponds to a high level of depressive and/or anxiety symptoms.
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment.
Title
Change in illness perception
Description
Will be measured using the The Brief Illness Perception Questionnaire (B-IPQ). B-IPQ consists of 9 items. Each item is rated on a 0-10 scale, with higher scores indicating a more threatening perception of the illness. The total score is calculated by summing the scores of all eight items, with a possible range of 0-80. Higher scores indicate worse illness perception.
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Change in Pain Catastrophizing
Description
Will be measured using the Pain Catastrophizing Scale (PCS-DK). Consists of 13 items. Each item is ranged from 0-4. A high score corresponds to a high degree of pain catastrophizing.
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Change in facial perception
Description
Will be measured using a self-constructed, self-reported questionaire
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Change in self-reported efficacy of treatment
Description
Will be measured using Patients Global Impression of Change (PGIC-DK). 1 item ranged 0-6. A high score corresponds to a subjective improvement.
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Change in how neck pain affects daily life
Description
Will be measured using the Neck Pain Disability Index (NDI-DK). 8 items ranged 0-6. A high score corresponds to a high impact on daily life.
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Changes in sleep quality
Description
Will be measured using the Pittsburgh Sleep Quality Index (PSQI-DK). seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.
Time Frame
Prior to intervention compared to 1 and 3 months after end of treatment
Title
Changes in the somatosensory function.
Description
Change in the somatosensory function from baseline to immediately after the completion of intervention (rTMS) and 1 month post-rTMS.
Time Frame
prior to rTMS intervention, immediately after rTMS intervention and 1 month after end of treatment
Title
Characterization of PTH headache phenotypes using a self-constructed headache questionaire.
Description
Characterization of PTH headache phenotypes into e.g. migraine-like or tension-type like using a self-constructed headache questionnaire.
Time Frame
3 months after mTBI
Title
Characterization of PTH headache phenotypes using the Headache Impact Scale.
Description
Characterization of PTH headache phenotypes into e.g. migraine-like or tension-type like using the Headache Impact Scale (HIT-6). HIT-6 is a 6 item scale. Each item is ranged from 0-5 ("never-always"). A high total score corresponds to a high impact of the headache on daily functioning.
Time Frame
3 months after mTBI
Title
Changes in headache phenotype using a self-constructed headache questionaire.
Description
Describing changes in the headache phenotype (e.g. migraine-like or tension-type like) longitudinally using a self-constructed headache questionnaire.
Time Frame
3, 9 and 12 months after mTBI
Title
Changes in headache phenotype using the Headache Impact Scale .
Description
Describing changes in the headache phenotype (e.g. migraine-like or tension-type like) longitudinally using the Headache Impact Scale (HIT-6). HIT-6 is a 6 item scale. Each item is ranged from 0-5 ("never-always"). A high total score corresponds to a high impact of the headache on daily functioning.
Time Frame
3, 9 and 12 months after mTBI

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Charlotte Nygaard, PhD student
Phone
004542428145
Email
chnyga@rm.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Simple Futarmal Kothari, Post.Doc.
Email
SIMKOT@rm.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jørgen Feldbæk Nielsen, Proffessor
Organizational Affiliation
Research Unit Hammel Neurocenter
Official's Role
Study Director
Facility Information:
Facility Name
Reseach Unit Hammel Neurocenter
City
Hammel
ZIP/Postal Code
8450
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jørgen Feldbæk Nielsen, Professor
Phone
+45 7841 9043
Email
joerniel@rm.dk

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31547466
Citation
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.
Results Reference
background
PubMed Identifier
33184973
Citation
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.
Results Reference
background

Learn more about this trial

GAIN Symptoms: Post-traumatic Headache

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