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Treating Persistent Post-concussion Symptoms With Exercise

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03895450
Recruitment Status : Active, not recruiting
First Posted : March 29, 2019
Last Update Posted : April 2, 2020
Sponsor:
Collaborator:
Hotchkiss Brain Institute, University of Calgary
Information provided by (Responsible Party):
University of Calgary

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 step-wise 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. 58 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 6 weeks post intervention.

Condition or disease Intervention/treatment Phase
Brain Injuries, Traumatic Concussion, Brain Mild Traumatic Brain Injury Post-Concussion Syndrome Behavioral: Aerobic Exercise Protocol Behavioral: Stretching Protocol Not Applicable

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 five days 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Investigator)
Masking Description: Allocation will be concealed through the use of sequentially numbered, opaque envelopes.
Primary Purpose: Treatment
Official Title: Improving Symptom Burden in Individuals With Persistent Post Concussive Symptoms: A Step-wise Aerobic Exercise Trial
Actual Study Start Date : April 16, 2019
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Aerobic Exercise Protocol (AEP)
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.
Behavioral: Aerobic Exercise Protocol
Participants randomized to AEP will be asked to exercise 20 minutes per day or until symptom exacerbation, 5-6 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.

Placebo Comparator: Stretching Protocol (SP)
The exercise testing for the stretching protocol to determine exercise prescription will be the same as described above.
Behavioral: Aerobic Exercise Protocol
Participants randomized to AEP will be asked to exercise 20 minutes per day or until symptom exacerbation, 5-6 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.

Behavioral: Stretching Protocol
Participants will follow a stretching protocol for 20 minutes a day, 6 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 Measures :
  1. Change in symptom burden [ 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 ]
    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 :
  1. Change in sleep duration [ Time Frame: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP ]
    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.

  2. Change in daytime sleepiness [ 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 ]
    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.

  3. Change in blood derived neurotrophic factor (BDNF) [ Time Frame: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP ]
    BDNF: serum BDNF, a neurotropic factor involved in neuronal repair after injury, will be analyzed for change in serum concentration

  4. Change in cytokine profile [ Time Frame: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP ]
    Cytokine profile: serum levels of multiple cytokines will be used to characterise chronic inflammatory changes

  5. Change in telomere length (TL) [ Time Frame: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP ]
    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.

  6. Change in fatigue [ 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 ]
    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."

  7. Change in anxiety [ Time Frame: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP ]
    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).

  8. Change in function related to headaches [ 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 ]
    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.

  9. Change in depression [ Time Frame: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP ]
    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).

  10. MRS quantification of GABA/Glutathione [ Time Frame: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-week of AEP ]
    Changes in GABA, glutathione and glutamate in the dorsolateral perefrontal cortex between AEP and SP group at 6 months



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03895450


Locations
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Canada, Alberta
University Of Calgary
Calgary, Alberta, Canada, T2N 4Z6
Sponsors and Collaborators
University of Calgary
Hotchkiss Brain Institute, University of Calgary
Investigators
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Principal Investigator: Chantel T Debert, MD MSc FRCPC University of Calgary
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Calgary
ClinicalTrials.gov Identifier: NCT03895450    
Other Study ID Numbers: REB18-1329
First Posted: March 29, 2019    Key Record Dates
Last Update Posted: April 2, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Concussion
Post-Concussion Syndrome
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Head Injuries, Closed
Wounds, Nonpenetrating