Traumatic Brain InjuryNCT06177509
Effect of Graded Aerobic Exercise in Mild Traumatic Brain Injury
A study testing Graded Aerobic Exercise in people with Traumatic Brain Injury and Mild Traumatic Brain Injury, run by Sunnaas Rehabilitation Hospital at 2 sites in Norway.
Trial summary
There is a paucity of knowledge about mechanisms behind mild traumatic brain injury (mTBI) subgroup's sustained problems, and effective interventions that can alleviate this disabling condition. Persistent Post-concussive Symptoms (PCS) affect between 20% and 30% of individuals after mTBI. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Traumatic Brain Injury, Mild Traumatic Brain Injury
- What is being tested?
- Graded Aerobic Exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 2 sitesNorway
- Study dates
- 17 Nov 2023to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of mild TBI as defined by the World Health Organization (WHO)
- Diagnosis of PCS based on ICD-10 criteria for a minimum of 3 months to a maximum of 2 years
- Age 18-60 years.
- Reduced tolerance to physical activity/exercise intolerance (self-reported worsening of symptoms such as dizziness, nausea or headache during physical activity and exercise). Or have not yet tried physical activity/exercise after the injury.
Who cannot join
- Other neurological or severe psychiatric conditions listed in the medical record.
- Heart-lung disease.
- Extremity injuries that prevent physical exercise
- Drug addiction
- Insufficient understanding of the Norwegian language (unable to follow instructions and/or fill in forms).
- Normal BCTT.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Norway2 sites, 2 recruiting
- Recruiting
Sunnaas rehabilitation hospital
Nesoddtangen, 1453
Marianne Løvstad, PhD, 4793452003, mar.lovstad@gmail.com
Lars Nysether, MD, Lars.Nysether@sunnaas.no
- Recruiting
Oslo University Hospital
Oslo
Nada Andelic, PhD, +4791817910, nadand@ous-hf.no
Ingerid Kleffelgaard, PhD, UXINFF@ous-hf.no
About this study
There is a paucity of knowledge about mechanisms behind mild traumatic brain injury (mTBI) subgroup's sustained problems, and effective interventions that can alleviate this disabling condition. Persistent Post-concussive Symptoms (PCS) affect between 20% and 30% of individuals after mTBI.
This Randomized Controlled Trial (RCT) will investigate whether graded aerobic exercise has a positive effect on symptom burden (including exercise intolerance) and Autonomic Nervous System (ANS) dysfunction in patients with PCS.
Read more
This study will expand upon previous work on adolescents with sport-related concussion in the acute phase. It will cover a wider age group and will include patients with persisting symptoms, thus providing knowledge on whether a sub-symptom threshold aerobic exercise program will alleviate symptom burden in adult patients with PCS.
Furthermore - looking into the relationship between mTBI and ANS function, this study is expected to contribute to a better understanding of the neurobiological factors involved in PCS. The results may also help developing targeted interventions to specific characteristics in persistent symptoms after mTBI.
Read the detailed description
Background: TBI is a public health challenge of considerable, but insufficiently recognized proportions. Therefore, a concerted effort should be made to reduce the burden and impact of TBI. Health care providers are in need of standardization of the medical examination and targeted individual interventions with potential to treat PCS.
Main purpose: The main purpose of this study is to evaluate whether a progressive, sub-symptom threshold aerobic exercise program in addition to ordinary rehabilitation will lead to clinically meaningful reduction in symptom burden, normalize exercise tolerance and improve health-related quality of life compared to a control group that only receives ordinary rehabilitation. In addition, changes in ANS function will be assessed in both the intervention and the control group.
Design: Randomized, controlled, single-blind parallel-group study with two measurement points; T0 at baseline and T1 after the intervention.
Method: The Buffalo Concussion Treadmill Test (BCTT) will be used to expose exercise intolerance, and participants with exercise intolerance will be randomized to the intervention group or the control group. Both groups will receive ordinary rehabilitation. The intervention group will in addition receive an individualized (based on BCTT) sub-symptom threshold aerobic exercise program for 12 weeks. To assess ANS function, Arterial spin labeling (ASL) MRI and Cold Pressor Test (CPT) will be performed at T0 and T1. Symptom burden will be assessed by Rivermead Post-concussion Symptom Questionnaire (RPQ) and other patient reported outcomes measurements including self-reported autonomic symptoms (the Composite Autonomic Symptom Score 31) will also be used.
Clinical relevance: Self-reported ANS, exercise intolerance testing, the CPT and ASL-MRI could prove to be useful clinical assessment tools to confirm the PCS-diagnosis and to determine readiness to return to preinjury level of day-to-day activities.
- Being tested
- Graded Aerobic Exercise
- Keywords
- post-concussion symptoms, autonomic nervous system dysfunction, Buffalo concussion treadmill test
- Medical subject headings
- Brain Injuries, Traumatic, Brain Concussion, Post-Concussion Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Graded Aerobic ExerciseOther
Participants will follow a sub-symptom aerobic exercise program (approx. 30 min) 3 - 5 times pr week for twelve weeks. Sub-symptom threshold aerobic exercise means to exercise at 80-90% of the maximum threshold heart rate achieved during the BCTT. To ensure proper exercise dose and progression, participants will be retested every three weeks. During the first three weeks, the participants will be offered one weekly guided exercise session. The other 2 - 4 weekly sessions the participants will carry out on their own, choosing activities based on experience, preferences and possibilities (e.g. walking, jogging, stationary bike, swimming). The intensity of the sub-symptom threshold aerobic exercise will be monitored using a heart rate monitor and the BORG scale. Compliance with the sub-symptom threshold aerobic exercise program will be recorded by the patients in an exercise diary, which is followed up by a weekly reminder over the phone/sms by a physiotherapist in the project.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group - Graded Aerobic Exercise | Experimental | Participants will follow a sub-symptom aerobic exercise program (approx. 30 min) 3 - 5 times pr week for twelve weeks. Sub-symptom threshold aerobic exercise means to exercise at 80-90% of the maximum threshold heart rate achieved during the BCTT. To ensure proper exercise dose and progression, participants will be retested every three weeks. During the first three weeks, the participants will be offered one weekly guided exercise session. The other 2 - 4 weekly sessions the participants will carry out on their own, choosing activities based on experience, preferences and possibilities (e.g. walking, jogging, stationary bike, swimming). The intensity of the sub-symptom threshold aerobic exercise will be monitored using a heart rate monitor and the BORG scale. Compliance with the sub-symptom threshold aerobic exercise program will be recorded by the patients in an exercise diary, which is followed up by a weekly reminder over the phone/sms by a physiotherapist in the project. Receives: Other: Graded Aerobic Exercise |
| Control group - Outpatient multidisciplinary follow-up (Treatment as usual - TAU) | No intervention | TAU includes assessment and treatment provided by a multidisciplinary outpatient rehabilitation team. Patients will undergo a medical examination and assessment of physical, cognitive, and mental health and functioning, followed by individually adapted rehabilitation program. The interdisciplinary team consists of a specialist in physical medicine and rehabilitation, (neuro)psychologist, occupational therapist, physiotherapist, and social worker. The main focus is on improving the level of function in everyday life and gradual return to work and education. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change on the Rivermead Post-concussion Symptom Questionnaire (RPQ)
A 16-item standardized and validated questionnaire designed to measure the severity of post-concussive symptoms following mTBI. The five-point ordinal scale ranges from 0 (no problem) to 4 (severe problem). The total score ranges from 0-64, with higher scores indicating a higher symptom load. RPQ has satisfactory psychometric properties and is widely used in mTBI and persistent post-concussive symptoms research. The minimal clinically important difference (MCID) is 4,6 points.
Measured: Baseline and 12 weeks
Secondary outcomes (6)
Change on the Cold Pressor Test Cold Pressor Test
The CPT is a test of ANS sympathetic activation that has been used to study a variety of populations. Submerging the hand in cold water stimulates the cold-sensitive nociceptive fibres, resulting in increased sympathetic neural activity, which will raise heart rate and blood pressure. Blunted and delayed cardiovascular responses, when compared to healthy subjects data, indicates ANS dysfunction. The participant's hand is submerged in ice water (approx. 0°C) for 120 seconds. Prior to, during, and after cooling of the hand, beat-to-beat blood pressure is measured by finger photoplethysmography (Finapres® NOVA; Finapres Medical Systems BV, Netherlands) and a three-lead electrocardiography (model DA100C; Biopac Systems Inc, Goleta, CA) is used to continuously record heart rate.
Measured: Baseline and 12 weeks
Change on Arterial spin labeling (ASL)
ASL MRI is an MRI sequence to quantitatively assess CBF. Alterations in CBF is well documented in moderate/severe TBI, and has been identified in animal models of mTBI and in children and athletes in the acute/subacute phase after mTBI. ANS sympathetic activation constricts and parasympathetic activation dilates cerebral blood vessels in turn altering CBF, which can be revealed by ASL. The scans will be performed on a 3.0T MRI scanner (Signa HDx, GE Medical Systems, Milwaukee, Wisconsin). The 3D ASL scan will automatically be processed into quantitative maps of global and regional CBF. Due to restricted resources, approximately 1/3 of the participants in each group (10 - 15 pr group) will be randomly allocated to an ASL MRI assessment at T0 and T1.
Measured: Baseline and 12 weeks
Change on the Buffalo Concussion Treadmill Test (BCTT)
The BCTT is a standardized incremental test of exercise tolerance. Exercise tolerance is tested by gradually increasing the load while walking on a treadmill. The test starts with speed set at 5.2 or 5.8 km/h (determined by participant's height) at 0% incline for the first minute. The speed is maintained and the incline is increased by 1% each minute. Every minute, overall post-concussion symptom burden is registered using a 0-10 numeric rating scale (NRS), rating of perceived exertion is obtained using Borg Rating of Perceived Exertion (RPE) and heart rate (HR) is obtained using a PolarH10 HR monitor. The test is stopped at symptom exacerbation defined as an increase of ≥ 3 points on the NRS (positive test). If voluntary exhaustion (RPE ≥ 17 on the 6 - 20 Borg rating scale) or 90% of age predicted maximum HR is reached without symptom exacerbation the test is stopped (negative test).Outcome measures from the BCTT are HR at- and time until stopping criteria are reached.
Measured: Baseline and 12 weeks
Change on 0-10 Numeric Rating Scale (NRS) in Concussion Symptom Burden
Reported concussion-specific symptoms during incremental tredmill test (BCTT) on a scale from 0 - 10, where 0 means no symptoms and 10 means worst symptoms ever experienced.
Measured: Baseline and 12 weeks
Change on Borg scale - Rating of Perceived Exertion (RPE)
Reported Percived Exortion during incremental tredmill test (BCTT) on a scale from 6- 20, 6 being no exertion and 20 being the maximum exortion.
Measured: Baseline and 12 weeks
Change in Heartrate (HR)
Heartrate is obtained by a Polar OH chest band HR monitor during incremental tredmill test (BCTT).
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2023
- Study start17 Nov 2023
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, controlled, single-blind parallel group design.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnaas Rehabilitation Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Oslo University Hospital, Oslo Metropolitan University
- Responsible party
- Sponsor
- Investigators
- Marianne Løvstad, Professor, Principal investigator, Head of psychology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06177509
- Sponsor's protocol ID
- Gradert trening ved mTBI
- Status last verified
- Dec 2023
- First submitted
- 5 Dec 2023
- Last updated
- 20 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Graded Aerobic Exercise in Mild Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT06177509
- Acronym / sponsor ID
- Gradert trening ved mTBI
- Keywords
- post-concussion symptoms, autonomic nervous system dysfunction, Buffalo concussion treadmill test
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Sunnaas Rehabilitation HospitalUniversity, hospital or other
- Collaborators
- Oslo University Hospital, Oslo Metropolitan University
- Study start
- 17 Nov 2023 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 20 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is a paucity of knowledge about mechanisms behind mild traumatic brain injury (mTBI) subgroup's sustained problems, and effective interventions that can alleviate this disabling condition. Persistent Post-concussive Symptoms (PCS) affect between 20% and 30% of individuals after mTBI.
This Randomized Controlled Trial (RCT) will investigate whether graded aerobic exercise has a positive effect on symptom burden (including exercise intolerance) and Autonomic Nervous System (ANS) dysfunction in patients with PCS.
This study will expand upon previous work on adolescents with sport-related concussion in the acute phase. It will cover a wider age group and will include patients with persisting symptoms, thus providing knowledge on whether a sub-symptom threshold aerobic exercise program will alleviate symptom burden in adult patients with PCS.
Furthermore - looking into the relationship between mTBI and ANS function, this study is expected to contribute to a better understanding of the neurobiological factors involved in PCS. The results may also help developing targeted interventions to specific characteristics in persistent symptoms after mTBI.
Detailed description
Background: TBI is a public health challenge of considerable, but insufficiently recognized proportions. Therefore, a concerted effort should be made to reduce the burden and impact of TBI. Health care providers are in need of standardization of the medical examination and targeted individual interventions with potential to treat PCS.
Main purpose: The main purpose of this study is to evaluate whether a progressive, sub-symptom threshold aerobic exercise program in addition to ordinary rehabilitation will lead to clinically meaningful reduction in symptom burden, normalize exercise tolerance and improve health-related quality of life compared to a control group that only receives ordinary rehabilitation. In addition, changes in ANS function will be assessed in both the intervention and the control group.
Design: Randomized, controlled, single-blind parallel-group study with two measurement points; T0 at baseline and T1 after the intervention.
Method: The Buffalo Concussion Treadmill Test (BCTT) will be used to expose exercise intolerance, and participants with exercise intolerance will be randomized to the intervention group or the control group. Both groups will receive ordinary rehabilitation. The intervention group will in addition receive an individualized (based on BCTT) sub-symptom threshold aerobic exercise program for 12 weeks. To assess ANS function, Arterial spin labeling (ASL) MRI and Cold Pressor Test (CPT) will be performed at T0 and T1. Symptom burden will be assessed by Rivermead Post-concussion Symptom Questionnaire (RPQ) and other patient reported outcomes measurements including self-reported autonomic symptoms (the Composite Autonomic Symptom Score 31) will also be used.
Clinical relevance: Self-reported ANS, exercise intolerance testing, the CPT and ASL-MRI could prove to be useful clinical assessment tools to confirm the PCS-diagnosis and to determine readiness to return to preinjury level of day-to-day activities.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, controlled, single-blind parallel group design.
| Arm | Type | Receives |
|---|---|---|
| Intervention group - Graded Aerobic Exercise | Experimental | Other: Graded Aerobic ExerciseParticipants will follow a sub-symptom aerobic exercise program (approx. 30 min) 3 - 5 times pr week for twelve weeks. Sub-symptom threshold aerobic exercise means to exercise at 80-90% of the maximum threshold heart rate achieved during the BCTT. To ensure proper exercise dose and progression, participants will be retested every three weeks. During the first three weeks, the participants will be offered one weekly guided exercise session. The other 2 - 4 weekly sessions the participants will carry out on their own, choosing activities based on experience, preferences and possibilities (e.g. walking, jogging, stationary bike, swimming). The intensity of the sub-symptom threshold aerobic exercise will be monitored using a heart rate monitor and the BORG scale. Compliance with the sub-symptom threshold aerobic exercise program will be recorded by the patients in an exercise diary, which is followed up by a weekly reminder over the phone/sms by a physiotherapist in the project. |
| Control group - Outpatient multidisciplinary follow-up (Treatment as usual - TAU) | No intervention | –TAU includes assessment and treatment provided by a multidisciplinary outpatient rehabilitation team. Patients will undergo a medical examination and assessment of physical, cognitive, and mental health and functioning, followed by individually adapted rehabilitation program. The interdisciplinary team consists of a specialist in physical medicine and rehabilitation, (neuro)psychologist, occupational therapist, physiotherapist, and social worker. The main focus is on improving the level of function in everyday life and gradual return to work and education. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Diagnosis of mild TBI as defined by the World Health Organization (WHO)
- Diagnosis of PCS based on ICD-10 criteria for a minimum of 3 months to a maximum of 2 years
- Age 18-60 years.
- Reduced tolerance to physical activity/exercise intolerance (self-reported worsening of symptoms such as dizziness, nausea or headache during physical activity and exercise). Or have not yet tried physical activity/exercise after the injury.
Key exclusion criteria (6 listed)
- Other neurological or severe psychiatric conditions listed in the medical record.
- Heart-lung disease.
- Extremity injuries that prevent physical exercise
- Drug addiction
- Insufficient understanding of the Norwegian language (unable to follow instructions and/or fill in forms).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Graded Aerobic ExerciseParticipants will follow a sub-symptom aerobic exercise program (approx. 30 min) 3 - 5 times pr week for twelve weeks. Sub-symptom threshold aerobic exercise means to exercise at 80-90% of the maximum threshold heart rate achieved during the BCTT. To ensure proper exercise dose and progression, participants will be retested every three weeks. During the first three weeks, the participants will be offered one weekly guided exercise session. The other 2 - 4 weekly sessions the participants will carry out on their own, choosing activities based on experience, preferences and possibilities (e.g. walking, jogging, stationary bike, swimming). The intensity of the sub-symptom threshold aerobic exercise will be monitored using a heart rate monitor and the BORG scale. Compliance with the sub-symptom threshold aerobic exercise program will be recorded by the patients in an exercise diary, which is followed up by a weekly reminder over the phone/sms by a physiotherapist in the project. | Other | Intervention group - Graded Aerobic Exercise |
Primary outcome
Change on the Rivermead Post-concussion Symptom Questionnaire (RPQ)
Time frame: Baseline and 12 weeks
A 16-item standardized and validated questionnaire designed to measure the severity of post-concussive symptoms following mTBI. The five-point ordinal scale ranges from 0 (no problem) to 4 (severe problem). The total score ranges from 0-64, with higher scores indicating a higher symptom load. RPQ has satisfactory psychometric properties and is widely used in mTBI and persistent post-concussive symptoms research. The minimal clinically important difference (MCID) is 4,6 points.
6 secondary outcomes
Change on the Cold Pressor Test Cold Pressor Test
Time frame: Baseline and 12 weeks
Change on Arterial spin labeling (ASL)
Time frame: Baseline and 12 weeks
Change on the Buffalo Concussion Treadmill Test (BCTT)
Time frame: Baseline and 12 weeks
Change on 0-10 Numeric Rating Scale (NRS) in Concussion Symptom Burden
Time frame: Baseline and 12 weeks
Change on Borg scale - Rating of Perceived Exertion (RPE)
Time frame: Baseline and 12 weeks
Change in Heartrate (HR)
Time frame: Baseline and 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marianne Løvstad, Professor principal investigator
Head of psychology
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Graded Aerobic Exercise in people with Traumatic Brain Injury and Mild Traumatic Brain Injury, run by Sunnaas Rehabilitation Hospital at 2 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marianne Løvstad, Professor (+4793452003, mar.lovstad@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change on the Rivermead Post-concussion Symptom Questionnaire (RPQ) (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2023.