Combinatory Rehabilitation for Traumatic Brain Injury

(CRUSH-IT Trial)

Overseen By Nancy Moore, MA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kessler Foundation

Must not be taking: Steroids, Benzodiazepines

Disqualifiers: Neurological disorders, Severe mental illness, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help individuals with moderate-to-severe traumatic brain injury (TBI) enhance their learning and memory skills. It combines the Kessler Foundation modified Story Memory Technique (KF-mSMT) with either aerobic or stretching exercises to determine the most effective combination. The goal is to assess whether adding aerobic exercise can significantly impact daily life, aiding in regaining independence and returning to work. This trial may suit those who have faced learning and memory challenges due to TBI for at least one year and are not currently active. Participants will engage in a supervised program three times a week for 12 weeks. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial requires that participants do not regularly take steroids or benzodiazepines. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining a special memory technique called the Kessler Foundation modified Story Memory Technique (KF-mSMT) with aerobic exercise can improve memory in people with traumatic brain injury (TBI). Studies have found that aerobic exercise is generally safe and can enhance memory. Participants in past studies who engaged in aerobic exercise experienced improvements in learning and memory, with few side effects.

Stretching exercises are also considered safe and are commonly used in rehabilitation programs. Stretching can improve flexibility and is usually well-tolerated by participants. When performed correctly, stretching exercises present no major safety concerns.

Since this trial is in an early phase, it primarily focuses on testing safety. Researchers will closely monitor participants to ensure the exercises are safe and well-tolerated. Prospective participants can expect careful supervision to ensure safety during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine physical exercise with cognitive rehabilitation, offering a dual approach to recovery from traumatic brain injury (TBI). Unlike typical TBI treatments that often focus solely on either physical rehabilitation or cognitive therapy, these experimental treatments integrate aerobic or stretching exercises with the Kessler Foundation modified Story Memory Technique (KF-mSMT). This unique combination aims to enhance both physical and cognitive recovery simultaneously, potentially leading to more comprehensive improvements for TBI patients. By addressing both body and mind, these treatments could set a new standard in TBI rehabilitation, offering hope for more effective recovery outcomes.

What evidence suggests that this trial's treatments could be effective for managing new learning and memory impairment in traumatic brain injury?

Research has shown that the Kessler Foundation modified Story Memory Technique® (KF-mSMT®) can moderately improve learning and memory in people with traumatic brain injuries (TBI). However, these improvements don't significantly impact daily life. In this trial, one group of participants will receive KF-mSMT® combined with aerobic exercise training (AET), which might boost the effects of KF-mSMT®. Studies have found that AET can enhance learning and memory by increasing brain activity. Another group will receive KF-mSMT® combined with stretching and toning exercises, which hasn't been studied as much but serves as a comparison to the AET approach. Overall, combining mental exercises with physical activity seems promising for better managing learning and memory issues in TBI. ^{1 2 3 5 6}

Who Is on the Research Team?

Nancy D Chiaravalloti, PhD

Principal Investigator

Kessler Foundation

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with moderate-to-severe traumatic brain injury (TBI) diagnosed at least a year ago. Participants should be physically inactive, right-handed, have memory impairments, and able to follow directions. They must not have severe mental illness, regular steroid or benzodiazepine use, significant vision impairment, unsafe conditions for MRI scans or high exercise risks.

Inclusion Criteria

I can follow directions well, as shown by my TICS-M score.

Having chronic medical conditions (e.g. diabetes) in addition to TBI will require approval to participate from a physician, consistent with PAR-Q+

I was diagnosed with a severe brain injury over a year ago.

Exclusion Criteria

Having moderate or high risk for exercise training contraindications (e.g. diabetes), defined as ≥1 YES on pages 2-3 of the Physical Activity Readiness Questionnaire for Everyone (PAR-Q+)

I regularly take steroids and benzodiazepines for medication effects.

Having a history of severe mental illness (e.g., schizophrenia, bipolar, severe major depression)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 12 weeks of supervised exercise training, with aerobic cycling or stretching and toning, combined with the Kessler Foundation modified Story Memory Technique for cognitive rehabilitation

12 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for changes in hippocampal volume, functional connectivity, and everyday memory performance

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KF-mSMT Plus Aerobic Exercise Training
• KF-mSMT Plus Stretching Exercise Training

Trial Overview The study tests the Kessler Foundation modified Story Memory Technique (KF-mSMT) combined with either aerobic exercise training (AET) or stretching exercises. It's a double-blind randomized controlled trial aiming to improve new learning and memory in TBI patients by comparing these two methods over a 12-week program.

How Is the Trial Designed?

Group I: KF-mSMT Plus Aerobic Exercise Training Experimental Treatment 1 Intervention

Participants will undergo 12 weeks of supervised aerobic cycling exercise training. During the last 8 weeks of cycling exercise, participants will also undergo treatment with the Kessler Foundation modified Story Memory Technique as an approach for cognitive rehabilitation.

Group II: KF-mSMT Plus Stretching Exercise Training Active Control 1 Intervention

Participants will undergo 12 weeks of supervised stretching and toning exercise training. During the last 8 weeks of stretching exercise, participants will also undergo treatment with the Kessler Foundation modified Story Memory Technique as an approach for cognitive rehabilitation.

Who Is Running the Clinical Trial?

Kessler Foundation

Lead Sponsor

Trials

190

Recruited

11,300+

Published Research Related to This Trial

This Phase I/II trial will assess the effects of 12 weeks of combined learning and memory rehabilitation with either aerobic cycling or stretching on cognitive outcomes in 60 individuals with moderate-to-severe traumatic brain injury (TBI).

The primary outcome will focus on improvements in new learning and memory, measured by the California Verbal Learning Test (CVLT)-III, potentially providing the first Class I evidence for the effectiveness of aerobic exercise in enhancing memory rehabilitation for TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of cognitive rehabilitation combined with aerobic exercise or stretching-and-toning on new learning and memory in persons with moderate-to-severe TBI: Protocol for a randomized controlled trial. Sandroff, BM., Weber, E., Wylie, GR., et al.[2023]

A survey of 555 Canadian rehabilitation clinicians revealed that the most common concussion management practices included education, sleep recommendations, goal setting, and energy management, with manual therapy also frequently used.

Only about one-third of clinicians incorporated aerobic exercise into their concussion management strategies, and those with a higher caseload of concussion patients were more likely to prescribe it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concussion Management Practices for Youth Who Are Slow to Recover: A Survey of Canadian Rehabilitation Clinicians. Dobney, DM., Gagnon, I.[2022]

In a study involving 360 veterans with moderate to severe traumatic brain injury (TBI), both cognitive-didactic and functional-experiential rehabilitation approaches showed similar long-term outcomes in terms of overall functional independence and return to work or school after one year.

However, participants receiving cognitive-didactic treatment demonstrated significantly better short-term cognitive function immediately after treatment, particularly benefiting younger individuals in terms of returning to work or school, while older participants with more education fared better in independent living with the functional-experiential approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation of traumatic brain injury in active duty military personnel and veterans: Defense and Veterans Brain Injury Center randomized controlled trial of two rehabilitation approaches. Vanderploeg, RD., Schwab, K., Walker, WC., et al.[2009]

Combined aerobic exercise with resistance/strength training and other activities significantly improves physical performance in the elderly, enhancing strength, balance, mobility, and reducing fall risk.

Compared to single aerobic exercise, combined exercise (CEX) showed superior benefits in various physical fitness measures, including gait speed and lower limb strength, highlighting the importance of multi-component training for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerobic Exercise Combination Intervention to Improve Physical Performance Among the Elderly: A Systematic Review. Bai, X., Soh, KG., Omar Dev, RD., et al.[2022]

In a study involving 34 geriatric patients aged 64 to 92, the addition of Intermittent Hypoxic-Hyperoxic Training (IHHT) to a multimodal training program significantly improved cognitive performance, as measured by the Dementia-Detection-Test, compared to a control group that received placebo breathing.

The experimental group also showed a greater improvement in functional exercise capacity, with a 24.1% increase in the 6-Minute-Walk-Test distance, compared to a 10.8% increase in the control group, indicating that IHHT enhances both cognitive and physical abilities in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adaptation to intermittent hypoxia-hyperoxia improves cognitive performance and exercise tolerance in elderly]. Bayer, U., Glazachev, OS., Likar, R., et al.[2018]

The neuromotor multicomponent training program (MCTP) significantly improved executive function and functional fitness in 56 older women over a 30-week period, showing better results than both control groups in tests like the Stroop test and Timed Up and Go test.

MCTP also positively impacted body composition and health-related quality of life (HRQOL), while both exercise groups (MCTP and CONTROL-EXE) experienced reductions in blood pressure, indicating its overall health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

120 min/week of neuromotor multicomponent training are enough to improve executive function and functional fitness in older women. Martinez-Navarro, I., Cordellat, A., Roldán, A., et al.[2021]

A 3-month community-based aerobic exercise training program showed a trend toward improved cardiorespiratory fitness (CRF) in individuals with traumatic brain injury (TBI), with an 8% increase in VO2peak compared to a 4% decrease in a stretching and toning group, indicating potential efficacy of aerobic exercise for this population.

The study demonstrated that while it is feasible to conduct exercise training in community settings for TBI patients, only 50% of participants adhered to the program, highlighting the need for strategies to improve adherence in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A proof-of-concept trial of a community-based aerobic exercise program for individuals with traumatic brain injury. Ding, K., Tarumi, T., Tomoto, T., et al.[2021]

In a study involving 62 participants with moderate-to-severe traumatic brain injury (TBI), the Kessler Foundation modified Story Memory Technique® (KF-mSMT®) did not show a significant treatment effect on learning slopes compared to a placebo, indicating that processing speed (PS) may not directly influence learning outcomes.

However, processing speed was found to be a significant predictor of post-treatment changes following KF-mSMT®, suggesting that cognitive dysfunctions beyond learning and memory can affect the overall benefits of cognitive rehabilitation for TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of information processing speed on benefit from learning and memory rehabilitation in TBI: a sub-analysis of the TBI-MEM trial. Chiaravalloti, ND., Costa, S., Armknecht, C., et al.[2023]

High-intensity interval training (HIIT) significantly enhances memory performance in sedentary older adults compared to moderate continuous training (MCT) and stretching, based on a study involving 64 participants.

Improvements in memory were correlated with increases in fitness levels, suggesting that exercise intensity may play a crucial role in cognitive benefits, although the study found no significant differences in brain-derived neurotrophic factor (BDNF) levels among the groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of aerobic exercise intensity on memory in older adults. Kovacevic, A., Fenesi, B., Paolucci, E., et al.[2021]

The modified Story Memory Technique (mSMT) significantly improved learning and memory in 69 participants with moderate to severe Traumatic Brain Injury (TBI) over 10 sessions in 5 weeks, showing medium effect sizes in various memory tasks.

This study provides strong evidence (class I) that mSMT enhances both objective memory and everyday memory, indicating its potential as an effective behavioral intervention for individuals with TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An RCT to Treat Learning Impairment in Traumatic Brain Injury: The TBI-MEM Trial. Chiaravalloti, ND., Sandry, J., Moore, NB., et al.[2022]

High-Intensity Functional Training (HIFT) combines elements of high-intensity interval training and strength exercises, leading to improved cardiovascular fitness and strength due to greater muscle recruitment compared to traditional aerobic exercises.

HIFT is associated with enhanced health markers, including cardiovascular and metabolic health, as well as cognitive function, which may contribute to reduced all-cause mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Intensity Functional Training: Molecular Mechanisms and Benefits. Ben-Zeev, T., Okun, E.[2022]

The modified Story Memory Technique (mSMT) significantly improved memory and learning in individuals with traumatic brain injury (TBI), as shown by changes in cerebral activation in key brain networks after treatment.

In a randomized clinical trial with 18 participants, the treatment group exhibited notable differences in brain activation compared to the placebo group, indicating that behavioral interventions like mSMT can effectively enhance cognitive function in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining the Efficacy of the Modified Story Memory Technique (mSMT) in Persons With TBI Using Functional Magnetic Resonance Imaging (fMRI): The TBI-MEM Trial. Chiaravalloti, ND., Dobryakova, E., Wylie, GR., et al.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1551714423002549

The effects of cognitive rehabilitation combined with ... The choice of AET as a complement to the KF-mSMT® for managing NLMI in TBI is based on the wealth of evidence of AET-related improvements on NLM [22,23], ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05716048

Study Details | NCT05716048 | Combinatory Rehabilitation ... By augmenting the effects of KF-mSMT with AET, we anticipate this treatment will ultimately help those with TBI-related NLMI return to the workforce, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37734538/

The effects of cognitive rehabilitation combined with ... This paper describes the protocol for a Phase I/II, parallel-group, blinded randomized controlled trial that compares the effects of 12-weeks of ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26147316/

Examining the Efficacy of the Modified Story Memory ... Examining the Efficacy of the Modified Story Memory Technique (mSMT) in Persons With TBI Using Functional Magnetic Resonance Imaging (fMRI): The TBI-MEM Trial.

5. kesslerfoundation.org kesslerfoundation.org/sites/default/files/2019-08/Chiaravalloti_Nancy_mSMT_18JAN18.pdf

the modified Story Memory Technique (mSMT) Does it work? ▫ Assessments before and after treatment. ▫ Neuropsychological assessment, neuroimaging, assessment of daily life. Can context ...

6. kesslerfoundation.org kesslerfoundation.org/press-release/kessler-foundation-scientists-publish-protocol-combining-aerobic-exercise-and

Kessler Foundation Scientists Publish Protocol for ... The article, “Rationale and methodology for examining the combination of aerobic exercise ... exercises combined with KF-mSMT. The primary ...