Clinical trial NCT05785000: Rehabilitation in Post Concussion Syndrome
Official title: Rehabilitation of Adult Patients With Post Concussion Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post-Concussion Syndrome
Keywords: Mild traumatic brain injury
Brain function
Magnetic Resonance Imaging
Buffalo Concussion Bike Test
Patient perception
360-degree evaluation
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: University College Copenhagen
First posted: 2023-03-27
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are recruited through our professional networks, via clinics, hospital emergency departments, general practitioners, physiotherapeutic clinics, flyers at educational institutions and patient associations. Inclusion age is 18-70 years, both genders. PCS symptoms of at least 4 weeks persistence after initial trauma and patients must be able to document the traumatic brain event from either emergency room or other medical doctor. Exclusion criteria: other diseases interfering with presentation of PCS symptoms.

Up to fifty healthy controls are included only in the MRI part. Healthy controls are recruited by advertising in public media. This part of the project is also constituted as a separate case control study comparing PCS patients and healthy controls

Seventy patients with PCS are randomized to either intervention as an add on to usual care or to control. Randomization is performed as a block-randomization with permuted block of size 2-6 generated via computer.
Primary purpose: TREATMENT

Brief summary: This project evaluates and quantifies the effects of an individually tailored exercise program applied to patients with long-lasting symptoms after concussion, minor traumatic brain injury, so-called Post-Concussion Syndrome (PCS). The project investigates the phenomenon Post Concussion Syndrome in four dimensions with a focus on both patient perspectives of PCS, an interventional physical program, a neurobiological basis for PCS through Magnetic Resonance Imaging (MRI) and finally through a 360-degree evaluation of the entire project involving patients and scientists in a reflective process.

Detailed description: The project has four parts

Aims and hypotheses:

1. The aim is to describe and nuance the subjective patient perceived aspects of living with PCS including the individual experiences of symptom provocation or relieve after the initial trauma. Part one is concept developing and involves qualitative in-depth interviews of patient experiences of obstacles for living a normal life with special emphasis of intolerance to activity and exercise.
2. The aim is to assess the effects of adding a 12 week individually tailored pulse-controlled aerobe exercise program to usual care. The hypothesis is that it is possible to increase the physical capacity measured by the number of minutes of pulse-training without symptom provocation. By increasing the number of minutes the threshold value of symptom provocation will be moved upwards for a training group (TG) of patients compared to a control group (CG) who carry on in their usual activities and treatments here defined as usual care.
3. The aim is to measure quantitative components of the neurobiological aspects of PCS by magnetic resonance imaging (MRI). The hypothesis is that patients with PCS have more leakiness of the blood-brain barrier (BBB) compared to healthy controls. In addition, PCS patients have disturbance of brain metabolism, abnormal microstructural tissue organization and abnormal brain activity. Furthermore, that intervention will normalize these MRI metrics in a training group (TG) compared to a control group (CG).
4. The aim is to obtain qualitative components of having patients and scientists evaluating the project. The evaluation will comprise participants involved, i.e. both patients in the 2 arms and researchers and the goal of this 360-degree evaluation is to describe perceived experiences of strength, weakness, possibility and threat (SWOT) of the intervention and ultimately prevent development of PSC after a minor traumatic brain injury.

Methods - the four parts:

1. Qualitative interviews of PCS participants focusing on individual perception of own situation, detailed symptom description, hindrance of living a normal life.
2. All PSC patients continue daily living and own developed coping strategies. The intervention is an add-on. We use Short Message Service (SMS) tracking every week obtaining details of wellbeing related to living with concussion. The intervention consists of bi-weekly one hour exercise guided by physiotherapist for 12 weeks. Clinical status is performed four times- before and after 12 weeks and with two interim assessments. We use the validated Buffalo Concussion Bike Test (BCBT ). Blood pressure, pulse rate, pulse oxymetri and exercise level are registered and we use Visual Analog Scale (VAS) and BORG Ratings of Perceived Exertion (BORG RPE) scales. In addition we use the Rivermead Post Concussion Questionnaire (RPCQ ).
3. Blood brain barrier (BBB) permeability is measured by Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) using a conventional MRI contrast agent. Both the leakiness (Ki) of the BBB, brain blood volume, capillary mean transit and distribution of transit times are estimated together with brain tissue perfusion (CBF). Other functional MRI measures are obtained such as the brain microstructural organization, measured by diffusion sensitive MRI and brain activity by Blood-oxygenation level dependent Imaging and brain lactate production as a measure of brain metabolism.
4. The 360-degree evaluation of the entire project is a joint, narrative process where patients, researcher and students involved sit together using a process evaluating principle. A data triangulation and a reflection of pros and cons of the project will guide the process. The evaluation is guided by an expert in process evaluation.

Eligibility criteria: Inclusion Criteria:

* Post concussion syndrome (PCS) diagnose according to WHO ICD-10 classification and documented by written statement from physician veritying a mild traumatic brain injury
* Longer lasting symptoms for at least 4 weeks after initial trauma
* If allocated to add-on exercise protocol participant must feel able to prioritize the intervention structure
* Communication language must be Danish

Exclusion Criteria:

* Other diseases blurring the diagnose PCS
* Other serious brain diseases
* Severe cardiovascular diseases precluding physical activity according to protocol

Primary outcomes:
measure: Change in Buffalo Concussion Bike Test from baseline measurement to week 12
timeFrame: Change in Buffalo Concussion Bike Test at week 12
Secondary outcomes:
measure: Changes in Rivermead Post Concussion Questionaire from baseline to week 12
timeFrame: Change in point score at week 12
measure: Changes in Fatique Scale Questionaire from baseline to week 12
timeFrame: Change in point score at week 12
measure: Change in Buffalo Concussion Bike Test from baseline measurement to week 4
timeFrame: Change in Buffalo Concussion Bike Test at week 4
measure: Change in Buffalo Concussion Bike Test from baseline to week 8
timeFrame: Change in Buffalo Concussion Bike Test at week 8
measure: Description of patient perspectives of living with PCS
timeFrame: Assessed at week 12
measure: Evaluation of the project
timeFrame: After completion of the 12 week intervention
measure: Change in Sms tracking domain one: "Physical Ability" of self reported well being in relation to commotio
timeFrame: Change in perceived physical ability at week 12
measure: Change in Sms tracking domain two: "Overall physical symptoms" of self reported well being in relation to commotio
timeFrame: Change in perceived overall physical symptoms at week 12
measure: Change in Sms tracking domain three: "Using the brain" of self reported well being in relation to commotio
timeFrame: Change in perception of "using the brain" at week 12
measure: Change in Sms tracking domain four: "Work ability" of self reported well being in relation to commotio
timeFrame: Change in perception of work ability
measure: Change in Sms tracking domain five: "Quality of daily living" of self reported well being in relation to commotio
timeFrame: Change in perception of quality of daily life
measure: Changes in Dynamic Gait Index Questionaire from baseline to week 12
timeFrame: Change in dynamic gait at week 12
measure: Change in blood brain barrier permeability from baseline to week 12
timeFrame: Change in blood brain barrier permeability at week 12
measure: Change of brain oxygen consumption from baseline to week 12
timeFrame: Change of brain oxygen consumption at week 12
measure: Change of brain diffusion from baseline to week 12
timeFrame: Change of brain diffusion at week 12
measure: Change of brain lactate from baseline to week 12
timeFrame: Change of brain lactate at week 12
measure: Case- control comparison; Blood brain barrier permeability
timeFrame: Comparison measurements at baseline
measure: Case-control comparison; Brain oxygen consumption
timeFrame: Comparison measurements at baseline
measure: Case-control comparison; Brain diffusion coefficient
timeFrame: Comparison measurements at baseline
measure: Case-control comparison; Brain lactate
timeFrame: Comparison measurements at baseline
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: University College Copenhagen
state: Region of Greater Copenhagen
Study officials:
affiliation: Faculty of Health and Medical Science, University of Copenhagen, Denmark
name: Henrik BW Larsson, Professor
role: PRINCIPAL_INVESTIGATOR
References: