Combination Therapies + Lifestyle Modifications for Traumatic Brain Injury

(CoINTEGRATE Trial)

Overseen by Hala Darwish, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Michigan

Must not be taking: Steroids

Disqualifiers: Severe depression, Substance abuse, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests if combining talking therapy, brain exercises, and lifestyle changes can help people with neurocognitive disorders live better lives by improving their thinking, brain function, and daily habits.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on intravenous or oral steroids for MS, you may not be eligible to participate.

What data supports the effectiveness of the treatment Combination Therapies + Lifestyle Modifications for Traumatic Brain Injury?

Research suggests that cognitive rehabilitation and behavioral health interventions, including Cognitive Behavioral Therapy (CBT) and lifestyle modifications, can help manage symptoms in individuals with traumatic brain injury (TBI). These approaches have shown promise in improving emotional distress and promoting healthy lifestyle changes, which are important for recovery. ^{1 2 3 4 5}

Is the combination of therapies and lifestyle modifications safe for people with traumatic brain injury?

The studies reviewed suggest that cognitive and lifestyle interventions, such as cognitive behavioral therapy and healthy lifestyle programs, are generally safe for people with traumatic brain injury. Participants in these programs reported positive experiences, and no significant safety concerns were noted. ^{1 2 4 5 6}

How is the treatment of combination therapies and lifestyle modifications for traumatic brain injury different from other treatments?

This treatment is unique because it combines multiple therapies, such as Cognitive Behavioral Therapy (CBT) and Cognitive Rehabilitation Therapy (CRT), with lifestyle changes to address the complex nature of traumatic brain injury (TBI), rather than focusing on a single therapy. This approach aims to target different aspects of TBI simultaneously, potentially leading to better outcomes than using one therapy alone. ^{3 7 8 9 10}

Research Team

Hala Darwish, PhD

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for adults over 50 with mild cognitive impairment (MCI) or those aged 21-65 with traumatic brain injury (TBI), multiple sclerosis (MS), or long COVID, experiencing certain levels of cognitive decline. They must be part of the Michigan medicine network and able to consent. Excluded are individuals with severe depression, suicidal thoughts, other major neurological conditions, recent MS relapse, diagnosed sleep disorders, sensory impairments, substance abuse issues, or currently in similar therapies.

Inclusion Criteria

I have been diagnosed with TBI, MS, Long COVID, or MCI.

I am over 50 with MCI or between 21-65 with another diagnosis and am treated within the Michigan medicine network.

Participants that can provide consent or legally authorized representative who can provide consent on their behalf

Exclusion Criteria

My cognitive abilities are within normal range for my age and education.

I have had mild cognitive impairment for over a year.

I experience symptoms like headache or dizziness from a brain injury.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive comprehensive multimodal individually tailored Cognitive Behavioral Therapy (CBT), Cognitive Rehabilitation Therapy (CRT), and modifiable lifestyle sessions

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CBT (Behavioural Intervention)
• CRT (Behavioural Intervention)
• Modifiable lifestyle factors (Behavioural Intervention)
• Usual care Psychoeducation (Behavioural Intervention)

Trial Overview The CoINTEGRATE study tests a tailored mix of Cognitive Behavioral Therapy (CBT), Cognitive Rehabilitation Therapy (CRT), and lifestyle changes against usual care to see if it improves life quality and community integration for people with neurocognitive disorders resulting from TBI or MS.

Participant Groups

Group I: CRT plus CBT and Lifestyle modifications Experimental Treatment 3 Interventions

Group II: Usual care Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

Marschall S. Runge

University of Michigan

Chief Executive Officer since 2015

MD, PhD

Karen McConnell

University of Michigan

Chief Medical Officer since 2020

MD

Findings from Research

In a study involving 123 Iraq/Afghanistan War veterans with mild traumatic brain injury, older age and poorer attention performance at baseline were linked to higher attendance rates in a 10-week Compensatory Cognitive Training (CCT) program.

These findings suggest that targeting neuropsychological factors, such as attention, could enhance adherence to cognitive interventions like CCT, potentially improving outcomes for veterans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Intervention Adherence in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury. Mahmood, Z., Clark, JMR., Jak, AJ., et al.[2021]

Psychiatric issues following traumatic brain injury (TBI) can severely affect a person's quality of life, and while treatment is challenging due to the complexity of symptoms, there is growing support for evidence-based strategies.

The review highlights the need for more rigorous research, including randomized controlled trials and innovative treatment models, to better understand and address the psychiatric conditions that arise after TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Psychiatric Problems After Traumatic Brain Injury. Fann, JR., Quinn, DK., Hart, T.[2022]

This systematic review analyzed 19 studies on non-pharmacologic interventions for managing persistent post-concussive symptoms (PCS) in military service members and veterans with mild traumatic brain injury (mTBI), highlighting the challenges posed by co-occurring conditions like PTSD and depression.

The review categorized interventions into four types—psychoeducational, cognitive rehabilitation, psychotherapeutic, and integrated behavioral health—emphasizing the need for more research to strengthen the evidence base for effective management of PCS in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of persistent post-concussive symptoms after mild traumatic brain injury: a systematic review of cognitive rehabilitation and behavioral health interventions in military service members and veterans. Cooper, DB., Bunner, AE., Kennedy, JE., et al.[2018]

Cognitive behavior therapy (CBT) tailored for individuals with acquired brain injury (ABI) significantly reduced emotional distress, as evidenced by improvements on the Symptom Checklist-90-Revised and the Depression Anxiety Stress Scales in a study of 20 participants.

The study demonstrated that both group and telephone formats of the adapted CBT were effective, highlighting its flexibility in delivery for individuals with chronic ABI, although no significant changes were noted in community integration or coping strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of cognitive behavior therapy in the treatment of emotional distress after acquired brain injury. Bradbury, CL., Christensen, BK., Lau, MA., et al.[2018]

A 12-month healthy lifestyle intervention for individuals with traumatic brain injury (TBI) was evaluated with 18 participants, revealing that support from staff and tracking of dietary and activity behaviors were key to perceived effectiveness.

Barriers to maintaining a healthy lifestyle included lack of motivation and challenges in meal preparation, suggesting that future programs should focus on enhancing self-regulation, providing prepared meals, and incorporating social support systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a 12-month lifestyle intervention by individuals with traumatic brain injury. Douglas, M., Driver, S., Callender, L., et al.[2020]

Individuals with a history of traumatic brain injury (TBI) are at a significantly higher risk for cardiovascular disease (CVD), highlighting the importance of addressing modifiable risk factors through diet.

A diet rich in fiber and nutrients, while low in added sugars and saturated fats, may provide the best protection against cardiovascular and neurological issues for those recovering from TBI, although more research is needed on dietary interventions in the chronic recovery phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Injury: How Dietary Patterns Impact Long-Term Outcomes. Patel, PR., Armistead-Jehle, P., Eltman, NR., et al.[2023]

Mindfulness-based cognitive therapy (MBCT) significantly reduced depression symptoms in individuals with traumatic brain injury (TBI) after an 8-week intervention, with medium to large effect sizes observed across all depression measures.

Participants also reported reduced pain intensity and increased energy levels following MBCT, highlighting its potential benefits beyond just alleviating depression in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mindfulness-based cognitive therapy: benefits in reducing depression following a traumatic brain injury. Bédard, M., Felteau, M., Marshall, S., et al.[2022]

The workshop convened by the National Institute of Neurological Disorders and Stroke emphasized the need for combination therapies in treating traumatic brain injury (TBI), as single therapies have consistently failed in clinical trials.

Participants recommended focusing on combinations of therapies that target different mechanisms and time-points, and suggested involving statisticians and the FDA early in the design of studies to improve the chances of success in developing effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapies for traumatic brain injury: prospective considerations. Margulies, S., Hicks, R.[2022]

Combination therapies (polytherapy) for traumatic brain injury (TBI) show promise, with 46% of studies indicating a positive additive or synergistic effect on behavioral outcomes, compared to only 19% showing negative interactions.

This review, which analyzed 37 studies, highlights the need for treatments that target multiple mechanisms of TBI, suggesting that a single therapy may not be sufficient for effective clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapies for neurobehavioral and cognitive recovery after experimental traumatic brain injury: Is more better? Kline, AE., Leary, JB., Radabaugh, HL., et al.[2019]

A systematic review of 10 randomized controlled trials identified that aquatic physical activity, mindfulness-based stress reduction (MBSR), computerized working-memory training, and blue-light therapy may effectively reduce fatigue after traumatic brain injury (TBI).

Despite these promising results, the overall quality of evidence was rated low to very low, indicating a need for further controlled trials to confirm the efficacy of these interventions for post-TBI fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complementary and alternative interventions for fatigue management after traumatic brain injury: a systematic review. Xu, GZ., Li, YF., Wang, MD., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Predictors of Intervention Adherence in Compensatory Cognitive Training for Veterans With a History of Mild Traumatic Brain Injury. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of Psychiatric Problems After Traumatic Brain Injury. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of persistent post-concussive symptoms after mild traumatic brain injury: a systematic review of cognitive rehabilitation and behavioral health interventions in military service members and veterans. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

The efficacy of cognitive behavior therapy in the treatment of emotional distress after acquired brain injury. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Evaluation of a 12-month lifestyle intervention by individuals with traumatic brain injury. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Brain Injury: How Dietary Patterns Impact Long-Term Outcomes. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Mindfulness-based cognitive therapy: benefits in reducing depression following a traumatic brain injury. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Combination therapies for traumatic brain injury: prospective considerations. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Combination therapies for neurobehavioral and cognitive recovery after experimental traumatic brain injury: Is more better? [2019]

10. England pubmed.ncbi.nlm.nih.gov

Complementary and alternative interventions for fatigue management after traumatic brain injury: a systematic review. [2020]