Ignite Creation Date:
2025-12-24 @ 12:19 PM
Ignite Modification Date:
2025-12-24 @ 12:19 PM
Study NCT ID:
NCT05857761
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-03-11
First Post:
2023-03-24
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
GAIN Symptoms: Post-traumatic Headache
Sponsor:
University of Aarhus
Organization:
Study Overview
Official Title:
Post-traumatic Headache: Phenotyping and Exploring Pathophysiological Insights and Novel Treatment Strategies
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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. Baseline biomarker levels in the blood samples from patients with mTBI will be compared to biomarker levels in blood samples from anonymous healthy age- and sex matched controls (blood donors) or published reference intervals from the litterature. 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.
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. Baseline biomarker levels in the blood samples from patients with mTBI will be compared to biomarker levels in blood samples from anonymous healthy age- and sex matched controls (blood donors) or published reference intervals from the litterature. 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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: