Exercise Treatment for Traumatic Brain Injury

((TOBI-SET) Trial)

Overseen By Juan J Lopez, BA

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: United States Naval Medical Center, San Diego

Disqualifiers: Recent TBI, Neurological disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a special exercise program, Sub-symptomatic Adaptable Exercise Treatment (SAET), might aid those with mild traumatic brain injuries (mTBI) in feeling better and resuming daily activities. The research aims to determine if this tailored exercise plan, designed to avoid worsening symptoms, is more effective than simple stretching exercises. Participants will engage in regular exercise sessions intended to enhance mental health and physical functioning. The trial seeks active service members who have experienced ongoing symptoms after at least one mild traumatic brain injury a month or more ago. As an unphased trial, it offers participants the chance to contribute to innovative research that could improve recovery strategies for mTBI.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this exercise treatment is safe for individuals with traumatic brain injury?

Research has shown that Sub-symptomatic Adaptable Exercise Treatment (SAET) is generally safe for individuals with mild traumatic brain injury (mTBI). Studies have found that exercising at a level that does not exacerbate symptoms can help alleviate ongoing symptoms experienced after a brain injury. These exercises are carefully adjusted to prevent symptom aggravation during activity.

One study involving individuals with mTBI demonstrated that aerobic exercise, performed without worsening symptoms, reduced symptoms and improved daily life. Participants reported no major negative effects from the exercise program, indicating it is well-tolerated.

In summary, SAET appears to be a safe method for managing symptoms after a mild brain injury. It emphasizes staying within safe limits to avoid symptom exacerbation while still reaping the benefits of exercise. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Sub-symptomatic Adaptable Exercise Treatment (SAET) for traumatic brain injury because it customizes exercise intensity to each participant's symptoms, adjusting the workout to stay below the threshold where symptoms might increase. This personalized approach is different from standard care, which often relies on general physical therapy and rest without such tailored adaptability. Additionally, SAET combines both aerobic and resistance training, which is not typically emphasized in regular treatment plans, offering a comprehensive exercise regimen that targets multiple aspects of recovery.

What evidence suggests that this trial's treatments could be effective for mTBI?

Research has shown that Sub-symptomatic Adaptable Exercise Treatment (SAET), which participants in this trial may receive, can help individuals with mild traumatic brain injury (mTBI) by reducing symptoms and improving overall function. A key component of SAET involves aerobic exercise that remains below the symptom-triggering threshold. This exercise type has proven safe and effective in reducing post-concussion symptoms and aiding individuals in returning to their usual activities. Studies also indicate that this exercise method can enhance exercise tolerance and lessen symptom intensity. These benefits suggest that SAET could be a promising option for those who continue to experience issues after an mTBI. ^{1 2 3 6 7}

Who Is on the Research Team?

Jason M Bailie, Phd

Principal Investigator

Traumatic Brain Injury Center of Excellence (TBICoE)

Are You a Good Fit for This Trial?

This trial is for military service members (SMs) who have experienced a mild traumatic brain injury (mTBI), commonly known as a concussion, and are still dealing with symptoms. The program aims to be adaptable for individual medical needs and available resources.

Inclusion Criteria

I am an active duty service member between 18 and 55 years old.

I have had a mild traumatic brain injury over a month ago.

I am a service member with ongoing symptoms.

Exclusion Criteria

History of moderate, severe, or penetrating TBI

Current substance use disorder

I had a brain injury within the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the Sub-symptomatic Adaptable Exercise Treatment (SAET) or the Stretching Control Group (SCG) intervention for 8 weeks, with sessions conducted both in-clinic and independently.

8 weeks

2 in-clinic visits per week, 3 independent sessions per week

Follow-up

Participants are monitored for changes in neurobehavioral symptoms, cognitive impairment, physiological adaptation, and occupational performance.

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Stretching Control Group (SCG)
• Sub-symptomatic Adaptable Exercise Treatment (SAET)

Trial Overview The study compares two approaches: Sub-symptomatic Adaptable Exercise Treatment (SAET), which is personalized exercise designed to reduce mTBI symptoms, versus a Stretching Control Group (SCG) that serves as the comparison group.

How Is the Trial Designed?

Group I: Sub-symptomatic Adaptable Exercise Treatment (SAET) Experimental Treatment 1 Intervention

Participants will attend two in-clinic sessions per week with either a licensed Physical Therapist or Exercise Physiologist and complete three sessions per week independently outside of the clinic. Each session will be 1 hour in duration, 5 days a week for 8 weeks, for a total of 40 hours. Participants will complete a combination of aerobic and resistance training exercises prescribed and adapted to the participant's personal needs based on evaluations by the Physical Therapist and Exercise Physiologist. Exercise will be adjusted to maintain sub-symptomatic levels, meaning that if a participant's neurobehavioral symptoms increase with activity, the intensity and/or exercise will be modified. Furthermore, participants will be asked to fill out an Exercise Habits Questionnaire (EHQ) in order to capture the exercises they are currently doing.

Group II: Stretching Control Group (SCG) Active Control 1 Intervention

Participants will attend two in-clinic sessions per week with either a licensed Physical Therapist or Exercise Physiologist and complete three sessions per week independently outside of the clinic. Each session will be 1 hour in duration, 5 days a week for 8 weeks, for a total of 40 hours. The stretching exercises are designed not to increase heart rate or have excessive head motion consist of static stretching and yoga based movements.

Who Is Running the Clinical Trial?

United States Naval Medical Center, San Diego

Lead Sponsor

Trials

110

Recruited

24,200+

Published Research Related to This Trial

Adherence to a personalized aerobic exercise prescription within the first week after a sport-related concussion (SRC) is linked to faster recovery, with adherent adolescents recovering in a median of 12 days compared to 21.5 days for non-adherents.

Interestingly, those who adhered to the exercise regimen were more symptomatic and had lower exercise tolerance at the start, indicating that initial exercise intolerance, rather than symptom severity, influences adherence to the exercise program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adolescents with Sport-Related Concussion Who Adhere to Aerobic Exercise Prescriptions Recover Faster. Chizuk, HM., Willer, BS., Cunningham, A., et al.[2023]

Aerobic exercise is increasingly recognized as a beneficial rehabilitation technique for individuals recovering from concussions, as it can help reduce symptoms and improve overall function.

The review highlights that while exercise is promising, the optimal parameters for recovery—such as frequency, duration, and intensity—are still not well defined, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Aerobic Exercise in Reducing Persistent Sport-related Concussion Symptoms. Howell, DR., Taylor, JA., Tan, CO., et al.[2020]

A study involving 12 patients with post-concussion syndrome showed that subsymptom threshold exercise training is safe and leads to significant improvements in exercise capacity and reduction of PCS symptoms over 2 to 3 weeks.

Participants were able to exercise longer and at higher heart rates without exacerbating symptoms, with athletes recovering faster than nonathletes, indicating that controlled exercise can be an effective treatment for PCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary study of subsymptom threshold exercise training for refractory post-concussion syndrome. Leddy, JJ., Kozlowski, K., Donnelly, JP., et al.[2022]

A study involving 56 adults with persistent post-concussive symptoms (PPCS) will assess the effectiveness of a 12-week progressive aerobic exercise program in reducing symptom burden, compared to a delayed start stretching protocol.

The primary outcome will be measured using the Rivermead Post-concussion Symptom Questionnaire, with additional evaluations of specific symptoms and brain metabolites, aiming to provide insights into the benefits of aerobic exercise for adults with PPCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving symptom burden in adults with persistent post-concussive symptoms: a randomized aerobic exercise trial protocol. Mercier, LJ., Fung, TS., Harris, AD., et al.[2023]

Subsymptom threshold aerobic exercise has been shown to improve symptoms in patients with postconcussion syndrome, based on a systematic review of 12 studies, indicating it may be a beneficial treatment option.

The exercise protocols typically involved 20 minutes of activity at 80% of the heart rate that triggered symptoms, performed 5-6 days a week, and no adverse events were reported, suggesting this approach is safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Subsymptom Threshold Aerobic Exercise for Persistent Concussion Symptoms in Patients With Postconcussion Syndrome: A Systematic Review. McIntyre, M., Kempenaar, A., Amiri, M., et al.[2021]

The study aims to evaluate the effectiveness of sub-symptom threshold aerobic exercise (SSTAE) combined with ordinary rehabilitation in improving symptoms and exercise tolerance in patients aged 18-60 with persistent post-concussion symptoms (PPCS) for over 3 months.

Preliminary findings from a feasibility trial indicate that SSTAE is safe and feasible, suggesting it could be a beneficial addition to rehabilitation for adults suffering from chronic symptoms after mild traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sub-symptom threshold aerobic exercise for patients with persisting post-concussion symptoms and exercise intolerance after mild traumatic brain injury - a study protocol with a nested feasibility study for a randomized controlled trial. Valaas, LV., Soberg, HL., Rasmussen, MS., et al.[2023]

Exercise interventions can significantly improve outcomes in individuals with traumatic brain injury (TBI) by reducing inflammation and promoting neuroplasticity, which are crucial for recovery.

Tailoring physical exercise programs to the specific type and severity of TBI can enhance their effectiveness, making exercise a valuable non-pharmacologic treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical exercise ameliorates deficits induced by traumatic brain injury. Archer, T., Svensson, K., Alricsson, M.[2012]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10155435/

Sub-symptom threshold aerobic exercise for patients with ... Recent studies suggest that SSTAE is safe, reduces PPCS, and may contribute to fewer activity limitations and increased participation [7, 17, 18] ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06561100

Treatment Optimization of Brain-injured Warfighters Prescribed sub-symptomatic adaptable exercise treatment (SAET) is a potential solution that promotes recovery needs following a TBI.

3. withpower.com withpower.com/trial/phase-brain-concussion-8-2023-85ed7

Exercise Treatment for Traumatic Brain Injury The study aims to evaluate the effectiveness of sub-symptom threshold aerobic exercise (SSTAE) combined with ordinary rehabilitation in improving symptoms ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37138202/

Sub-symptom threshold aerobic exercise for patients with ... Sub-symptom threshold aerobic exercise for patients with persisting post-concussion symptoms and exercise intolerance after mild traumatic brain injury - a ...

5. trialx.com trialx.com/clinical-trials/listings/267638/sub-symptom-threshold-aerobic-exercise-after-mild-traumatic-brain-injury/

Sub-symptom Threshold Aerobic Exercise After Mild ... The hypothesis is that sub-symptom training will reduce the symptom pressure, normalize exercise tolerance, reduce patient-specific activity ...

6. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1482266/full

Evaluating a 12-week aerobic exercise intervention in ... A total of 50 adults with a diagnosis of mTBI, PPCS and exercise intolerance completed a 12-week sub-symptom threshold aerobic exercise intervention either ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6089233/

Exercise is Medicine for Concussion - PMC - PubMed Central This article reviews recent observational and experimental data and presents the evidence that sub-threshold aerobic exercise normalizes the cerebrovascular ...