Combination Therapies + Lifestyle Modifications for Traumatic Brain Injury

(CoINTEGRATE Trial)

Overseen By Hala Darwish, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must not be taking: Steroids

Disqualifiers: Severe depression, Substance abuse, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining different therapies with lifestyle changes can help people with brain-related conditions such as mild traumatic brain injury (TBI), multiple sclerosis (MS), long COVID, or mild cognitive impairment (MCI). The goal is to determine if these treatments can improve everyday life and social involvement compared to standard care. Potential participants include those with one of these conditions who face challenges like memory problems or difficulty processing information. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance treatment options for brain-related conditions.

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.

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

Research shows that both Cognitive Behavioral Therapy (CBT) and Cognitive Rehabilitation Therapy (CRT) are safe and generally well-tolerated. Studies have found that CBT reduces negative thoughts and behaviors, improving mental health and quality of life. Most people can handle it without serious side effects.

For CRT, research indicates it helps individuals with brain injuries enhance their thinking skills for daily activities. Strong evidence of harmful side effects with CRT is lacking.

Lifestyle changes, such as adjusting diet, exercise, or daily habits, are usually safe and can improve overall well-being.

These treatments have been studied separately and have a strong safety record. Therefore, combining them is also expected to be safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination of Cognitive Rehabilitation Therapy (CRT), Cognitive Behavioral Therapy (CBT), and lifestyle modifications for traumatic brain injury because it offers a comprehensive approach that goes beyond usual care. Unlike traditional treatments that often focus solely on immediate medical interventions, this approach integrates mental health support with lifestyle changes, potentially enhancing recovery. By addressing cognitive and psychological aspects alongside daily habits, this method aims to improve overall quality of life for patients, making it a promising avenue for holistic healing.

What evidence suggests that this trial's treatments could be effective for traumatic brain injury?

Research has shown that certain therapies can improve the lives of people with traumatic brain injuries (TBI). In this trial, one group of participants will receive a combination of Cognitive Rehabilitation Therapy (CRT), Cognitive Behavioral Therapy (CBT), and lifestyle modifications. CRT encourages mentally stimulating activities, aiding recovery. CBT has proven effective in enhancing mental health and quality of life for those with mild to moderate brain injuries. Additionally, lifestyle changes and other behavioral interventions have played a crucial role in improving care for TBI patients. Together, these methods aim to help individuals feel more connected to their communities and increase overall life satisfaction. ^{1 3 4 5 6}

Who Is on the Research Team?

Hala Darwish, PhD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

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.

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

I have cognitive issues in learning, memory, or processing speed.

Exclusion Criteria

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

I have had mild cognitive impairment for over a year.

History of TBI (except for participants with TBI)

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• CBT
• CRT
• Modifiable lifestyle factors
• Usual care Psychoeducation

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5619134/

Cognitive rehabilitation following traumatic brain injury - PMC The study results yielded relevant information on a structured cognitive rehabilitation service, representing an alternative for patients and families ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10858765/

The importance of behavioral interventions in traumatic ... Results: Behavioral interventions have demonstrated their effectiveness in addressing various aspects of TBI care. They have been instrumental ...

3. research.aota.org research.aota.org/ajot/article/76/Supplement%202/7613393160/23919/Cognitive-Behavioral-Therapy-Interventions-for

Cognitive Behavioral Therapy Interventions for Adults With ... Across studies, individual CBT-based interventions resulted in significantly improved psychological well-being and quality of life for both mild ...

4. sciencedirect.com sciencedirect.com/topics/neuroscience/cognitive-rehabilitation-therapy

Cognitive Rehabilitation Therapy - an overview Cognitive rehabilitation therapy (CRT) refers to treatments designed to improve patients' participation in cognitively demanding activities by either ...

5. nap.nationalacademies.org nap.nationalacademies.org/download/13220

Cognitive Rehabilitation Therapy for Traumatic Brain Injury 2011. Cognitive Rehabilitation. Therapy for Traumatic Brain Injury: Evaluating the Evidence. Washington, DC: The National Academies Press.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8489050/

Cognitive–behavioral therapy for management of mental ... Cognitive–behavioral therapy (CBT) helps individuals to eliminate avoidant and safety-seeking behaviors that prevent self-correction of faulty beliefs.