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Treating Persistent Post-concussion Symptoms With Exercise

Primary Purpose

Brain Injuries, Traumatic, Concussion, Brain, Mild Traumatic Brain Injury

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Aerobic Exercise Protocol
Stretching Protocol
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Injuries, Traumatic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of mild traumatic brain injury (mTBI) based on the American Congress of Rehabilitation Medicine (ACRM) criteria.
  • mTBI occurrence from 3 months to 5 years from study start date
  • Diagnosis of persistent post-concussion symptoms based on the ICD-10 criteria.
  • Cleared for physical activity based on The Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) by treating physician
  • at low risk for cardiopulmonary disease in accordance with the American College of Sports Medicine guidelines
  • exercise intolerance (inability to exercise at pre-injury intensity/duration due to acute presentation of symptoms)

Exclusion Criteria:

  • past medical history of neurological disorders (i.e., Parkinson's disease, neuromuscular disorders)
  • contraindications to MRI
  • cardiopulmonary disorder
  • chronic musculoskeletal condition
  • psychiatric disorder other than depression and/or anxiety (i.e., schizophrenia, bipolar disorder)
  • cancer
  • pregnancy

Sites / Locations

  • University Of Calgary

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Aerobic Exercise Protocol (AEP)

Stretching Protocol (SP)

Arm Description

Symptom threshold will be determined at baseline and repeated every 3 weeks using the Buffalo Concussion Treadmill Test. Briefly, there will be an initial 4min warm up at 1.7mph. The protocol will start with treadmill speed se to 3.3 mph and 0.0% incline. Each subsequent minute, the incline will increase by 1.0% to a max of 15%. At 15% grade, if the participant is still able to continue, treadmill speed will increase by 0.4mph each minute. Heart rate (HR) and rating of perceived excretion (RPE Borg scale) will be measured every minute. The test will be terminated upon symptom exacerbation at which time HR and RPE will be recorded. Every 3 weeks the symptom threshold test will be repeated for all participants and exercise prescription will be adjusted accordingly.

The exercise testing for the stretching protocol to determine exercise prescription will be the same as described above.

Outcomes

Primary Outcome Measures

Change in symptom burden
Rivermead Post-concussion Symptoms Questionnaire (RPQ): an instrument developed to assess the frequency and severity of 16 common post-concussion symptoms. On this paper and pencil tool, patients rate the extent to which their symptoms (compared to their pre-injury levels) have become more problematic over the past 24 hours using a rating scale from 0-4 (0=not experienced, 1=no more of a problem, 2=mild problem, 3=moderate problem, 4=severe problem). A total symptom score is calculated out of 64.

Secondary Outcome Measures

Change in sleep duration
Wrist actigraphy confirmed by a sleep diary. An actigraph (MotionWatch8 [CamNTech]) watch will be worn on the non-dominant wrist during nighttime hours. Actigraphy results will be confirmed by a sleep diary completed in the morning.
Change in daytime sleepiness
Epworth Sleepiness Scale (ESS): measure of daytime sleepiness. This scale rates the chance of dozing off on a scale of 0-3 (0= would never doze, 1= slight chance of dozing, 2= moderate chance of dozing, 3=high chance of dozing) in 8 different situations.
Change in blood derived neurotrophic factor (BDNF)
BDNF: serum BDNF, a neurotropic factor involved in neuronal repair after injury, will be analyzed for change in serum concentration
Change in cytokine profile
Cytokine profile: serum levels of multiple cytokines will be used to characterise chronic inflammatory changes
Change in telomere length (TL)
Telomeres are non-coding sequences of DNA that are found at the end of linear eukaryotic chromosomes thought to play a role in DNA strand repair. TL length will be analyzed using whole blood collected across time points.
Change in fatigue
Fatigue Severity Scale (FSS): 9 instrument questionnaire. Each item is rated on a 7 point likert scale (1= Strongly disagree, 7=strongly agree). Total score is calculated by adding the score from each item producing a total out of 63. A final item asks to "Please mark "X" on a number line which describes your global fatigue with 0 being worst and 10 being normal."
Change in anxiety
Generalized Anxiety Disorder (GAD-7): a 7-item tool where each item is rated on frequency over a 2 week period based on a 0-3 scale (0=not at all, 1=several days, 2=more than half the days, 3=nearly every day). The total score ranges from 0 to 21, with scores indicating severity of anxiety (ie. 0-5= mild, 6-10= moderate, 11-15= moderately severe, 16-21= very severe).
Change in function related to headaches
Headache Impact Test (HIT-6): a global measure of headache impact. Addresses the 6 categories of headache impact including social, ADL, and cognitive functioning, vitality, psychological distress, and severity of headache pain. Each question is scored on a 5 point scale (never, rarely, sometimes, very often, always). Total score can range from 36-78, with higher total score indicating greater impact.
Change in depression
Patient Health Questionnaire-9 (PHQ-9): 9 item tool to assess the presence and severity of depressive symptoms. Each item is rated based on the frequency of occurrence in the past 2 weeks and is graded ona 0-3 scale (0=not at all, 1=several days, 2= more than half of the days, 3= nearly every day). A stand-alone question asks to rate how difficult problems have made completing tasks at home, doing work, and getting along with people. This is graded on a 4-point scale from not difficult at all to extremely difficult. Total score is calculated out of 27, with the value indicating severity of depression (ie. 0-4= none to mild, 5-9= mild, 10-14= moderate, 15-19= moderately severe, and 20-27= very severe).
MRS quantification of GABA/Glutathione
Changes in GABA, glutathione and glutamate in the dorsolateral perefrontal cortex between AEP and SP group at 6 months

Full Information

First Posted
February 11, 2019
Last Updated
October 18, 2023
Sponsor
University of Calgary
Collaborators
Hotchkiss Brain Institute, University of Calgary
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1. Study Identification

Unique Protocol Identification Number
NCT03895450
Brief Title
Treating Persistent Post-concussion Symptoms With Exercise
Official Title
Improving Symptom Burden in Individuals With Persistent Post Concussive Symptoms: A Step-wise Aerobic Exercise Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
May 24, 2019 (Actual)
Primary Completion Date
February 20, 2023 (Actual)
Study Completion Date
February 20, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Calgary
Collaborators
Hotchkiss Brain Institute, University of Calgary

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 objective of this study is to investigate an aerobic exercise program as a treatment for adults with persistent post-concussive symptoms (PPCS) following mild traumatic brain injury. In this delayed-start trial participants will be initially randomized into either a 6-week low-impact stretching protocol or 12-week aerobic exercise protocol. Following the completion of the stretching protocol participants will continue on to complete the aerobic exercise protocol in full. 56 participants aged 18-65 yrs will be recruited from the Calgary Brain Injury Program (CBIP), including the Early Concussion Education Program at Foothills Medical Centre, Calgary Pain Program, University of Calgary Sports Medicine Centre acute concussion clinic and a physiotherapy clinic (Tower Physio) all of which are located in Calgary, Alberta, Canada. Participants will complete an online follow up (symptom questionnaires and questions regarding exercise behaviour) 3 and 9 weeks post intervention.
Detailed Description
Demographic information will be collected prior to study participation and include age, sex, education, family medical history, past medical history, concussion history, litigious status and medication use. The PAR-Q+ questionnaire will be completed to determine readiness for exercise by a physician. Baseline questionnaires will be completed, such as the Fatigue Severity Scale (FSS), Generalized Anxiety Disorder Scale (GAD-7), Headache Intensity Scale-6 (HIT-6), Patient Health Questionnaire(PHQ-9), Epworth Sleepiness Scale(ESS) and Quality of Life After Brain Injury(QOLIBRI), Rivermead Post Concussion Symptoms Questionnaire (RPQ), Modified Godin Leisure-Time Exercise Questionnaire(GLTQ), Rapid Assessment Disuse Index (RADI) and Postconcusion Syndrome Checklist (PCSC). Pre- and post-intervention blood samples will be collected from all participants. Participants will be asked to perform a tactile assessment pre- and post-intervention. Sleep will be monitored using wrist-based actigraphy and a sleep diary for 3-6 days/nights prior to the intervention start and for five days following completion of the exercise protocol. Pre and post magnetic resonance spectroscopy (MRS) will also be completed. Participants will be randomized to a structured aerobic exercise protocol (AEP) or stretching protocol, followed by aerobic exercise protocol(SP+AEP) with a random number generator. Both groups will undergo exercise testing using the Buffalo Concussion Treadmill Test to determine exercise prescription. Upon completion of SP, participants will continue on to the AEP and complete it in full. Following the exercise protocols, all questionnaires will be completed post-intervention. At 3 and 9 weeks following protocol completion, online follow surveys will be completed to assess symptom burden (RPQ, QOLIBRI, HIT-6, ESS, FSS) along with questions regarding current exercise.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Injuries, Traumatic, Concussion, Brain, Mild Traumatic Brain Injury, Post-Concussion Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Investigator
Masking Description
Allocation will be concealed through the use of sequentially numbered, opaque envelopes.
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aerobic Exercise Protocol (AEP)
Arm Type
Experimental
Arm Description
Symptom threshold will be determined at baseline and repeated every 3 weeks using the Buffalo Concussion Treadmill Test. Briefly, there will be an initial 4min warm up at 1.7mph. The protocol will start with treadmill speed se to 3.3 mph and 0.0% incline. Each subsequent minute, the incline will increase by 1.0% to a max of 15%. At 15% grade, if the participant is still able to continue, treadmill speed will increase by 0.4mph each minute. Heart rate (HR) and rating of perceived excretion (RPE Borg scale) will be measured every minute. The test will be terminated upon symptom exacerbation at which time HR and RPE will be recorded. Every 3 weeks the symptom threshold test will be repeated for all participants and exercise prescription will be adjusted accordingly.
Arm Title
Stretching Protocol (SP)
Arm Type
Placebo Comparator
Arm Description
The exercise testing for the stretching protocol to determine exercise prescription will be the same as described above.
Intervention Type
Behavioral
Intervention Name(s)
Aerobic Exercise Protocol
Intervention Description
Participants randomized to AEP will be asked to exercise 30 minutes per day or until symptom exacerbation, 5 days per week either at home, outdoors or at a fitness facility of choice. The assigned exercise prescription target will be 70-80% of the maximum HR achieved during the treadmill test. HR monitors will be provided to monitor exercise intensity.
Intervention Type
Behavioral
Intervention Name(s)
Stretching Protocol
Intervention Description
Participants will follow a stretching protocol for 30 minutes a day, 5 days a week. Individuals in the SP group will be given a booklet explaining a low-impact breathing and stretching program developed at the University of Buffalo. All stretches will explained and demonstrated by a member of the study team prior to commencement of the program. Stretches focus on lower extremity muscles. During the protocol HR should be low as to not exceed 50% of age predicted max. A HR monitor will be worn during stretching.
Primary Outcome Measure Information:
Title
Change in symptom burden
Description
Rivermead Post-concussion Symptoms Questionnaire (RPQ): an instrument developed to assess the frequency and severity of 16 common post-concussion symptoms. On this paper and pencil tool, patients rate the extent to which their symptoms (compared to their pre-injury levels) have become more problematic over the past 24 hours using a rating scale from 0-4 (0=not experienced, 1=no more of a problem, 2=mild problem, 3=moderate problem, 4=severe problem). A total symptom score is calculated out of 64.
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP
Secondary Outcome Measure Information:
Title
Change in sleep duration
Description
Wrist actigraphy confirmed by a sleep diary. An actigraph (MotionWatch8 [CamNTech]) watch will be worn on the non-dominant wrist during nighttime hours. Actigraphy results will be confirmed by a sleep diary completed in the morning.
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP
Title
Change in daytime sleepiness
Description
Epworth Sleepiness Scale (ESS): measure of daytime sleepiness. This scale rates the chance of dozing off on a scale of 0-3 (0= would never doze, 1= slight chance of dozing, 2= moderate chance of dozing, 3=high chance of dozing) in 8 different situations.
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP
Title
Change in blood derived neurotrophic factor (BDNF)
Description
BDNF: serum BDNF, a neurotropic factor involved in neuronal repair after injury, will be analyzed for change in serum concentration
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP
Title
Change in cytokine profile
Description
Cytokine profile: serum levels of multiple cytokines will be used to characterise chronic inflammatory changes
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP
Title
Change in telomere length (TL)
Description
Telomeres are non-coding sequences of DNA that are found at the end of linear eukaryotic chromosomes thought to play a role in DNA strand repair. TL length will be analyzed using whole blood collected across time points.
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP
Title
Change in fatigue
Description
Fatigue Severity Scale (FSS): 9 instrument questionnaire. Each item is rated on a 7 point likert scale (1= Strongly disagree, 7=strongly agree). Total score is calculated by adding the score from each item producing a total out of 63. A final item asks to "Please mark "X" on a number line which describes your global fatigue with 0 being worst and 10 being normal."
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP
Title
Change in anxiety
Description
Generalized Anxiety Disorder (GAD-7): a 7-item tool where each item is rated on frequency over a 2 week period based on a 0-3 scale (0=not at all, 1=several days, 2=more than half the days, 3=nearly every day). The total score ranges from 0 to 21, with scores indicating severity of anxiety (ie. 0-5= mild, 6-10= moderate, 11-15= moderately severe, 16-21= very severe).
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP
Title
Change in function related to headaches
Description
Headache Impact Test (HIT-6): a global measure of headache impact. Addresses the 6 categories of headache impact including social, ADL, and cognitive functioning, vitality, psychological distress, and severity of headache pain. Each question is scored on a 5 point scale (never, rarely, sometimes, very often, always). Total score can range from 36-78, with higher total score indicating greater impact.
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP
Title
Change in depression
Description
Patient Health Questionnaire-9 (PHQ-9): 9 item tool to assess the presence and severity of depressive symptoms. Each item is rated based on the frequency of occurrence in the past 2 weeks and is graded ona 0-3 scale (0=not at all, 1=several days, 2= more than half of the days, 3= nearly every day). A stand-alone question asks to rate how difficult problems have made completing tasks at home, doing work, and getting along with people. This is graded on a 4-point scale from not difficult at all to extremely difficult. Total score is calculated out of 27, with the value indicating severity of depression (ie. 0-4= none to mild, 5-9= mild, 10-14= moderate, 15-19= moderately severe, and 20-27= very severe).
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP
Title
MRS quantification of GABA/Glutathione
Description
Changes in GABA, glutathione and glutamate in the dorsolateral perefrontal cortex between AEP and SP group at 6 months
Time Frame
Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-week of AEP

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of mild traumatic brain injury (mTBI) based on the American Congress of Rehabilitation Medicine (ACRM) criteria. mTBI occurrence from 3 months to 5 years from study start date Diagnosis of persistent post-concussion symptoms based on the ICD-10 criteria. Cleared for physical activity based on The Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) by treating physician exercise intolerance (inability to exercise at pre-injury intensity/duration due to acute presentation of symptoms) Exclusion Criteria: past medical history of neurological disorders (i.e., Parkinson's disease, neuromuscular disorders) contraindications to MRI cardiopulmonary disorder chronic musculoskeletal condition psychiatric disorder other than depression and/or anxiety (i.e., schizophrenia, bipolar disorder) cancer pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chantel T Debert, MD MSc FRCPC
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
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Treating Persistent Post-concussion Symptoms With Exercise

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