Neuromodulation + Neurorehabilitation for Concussion + PTSD

Recruiting at 2 trial locations

Overseen By Ann Guernon, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Must not be taking: Antipsychotics, Trazodone, Tramadol, others

Disqualifiers: Epilepsy, Psychotic disorders, Heart disease, others

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

Compensation: Varies

Number of Visits: 35

Duration: 10 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination treatment for individuals experiencing attention issues after a mild traumatic brain injury (mTBI), with or without PTSD. It combines computer-based attention training (APT) and magnetic stimulation (iTBS, or Intermittent Theta Burst Stimulation) to evaluate their effectiveness in improving attention problems. Participants will join one of four groups, each testing different combinations of these treatments to determine the most effective approach. Eligible participants have experienced mTBI for at least three months and face attention challenges in daily life. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance attention treatments for mTBI patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as CNS stimulants, during participation. If your mental health medication dosage has changed in the last 30 days, you may not be eligible. Please consult with the trial team for specific guidance on your medications.

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

Research has shown that Attention Process Training (APT) is safe and well-tolerated. It improves attention skills after brain injuries, such as concussions, without causing significant side effects.

Intermittent theta burst stimulation (iTBS) is also safe. It effectively treats conditions like PTSD and depression by using short magnetic pulses to stimulate the brain. Studies report no major safety concerns, and participants usually handle the treatment well.

Both APT and iTBS have strong safety records. For those considering joining a trial, these treatments have been studied and found to be safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine neuromodulation and cognitive training to tackle concussion and PTSD in a new way. Unlike standard treatments that often focus on medication or traditional therapy, this approach uses intermittent theta-burst stimulation (iTBS) targeting the brain's dorsolateral prefrontal cortex, potentially enhancing brain plasticity and cognitive function. Additionally, the Attention Process Training (APT) program offers a novel computer-based cognitive training experience. Together, these treatments could offer faster and more effective relief from symptoms by directly engaging and retraining the brain's pathways.

What evidence suggests that this trial's treatments could be effective for concussion and PTSD?

Research has shown that both APT (Attention Process Training) and iTBS (intermittent theta-burst stimulation) hold promise for alleviating symptoms of mild traumatic brain injury (mTBI) and PTSD (post-traumatic stress disorder). APT has successfully improved attention and cognitive skills in individuals with brain injuries, regardless of the injury's severity or timing. iTBS, meanwhile, quickly alleviates PTSD symptoms and has demonstrated positive effects on depression. In this trial, participants will be assigned to different treatment arms to evaluate these therapies' effects. Some will receive real APT combined with real iTBS, while others will receive placebo versions of one or both treatments. Early evidence suggests that combining these therapies could significantly enhance attention and cognitive skills. ^{3 6 7 8 9}

Who Is on the Research Team?

Theresa LB Pape, Dr.PH

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 who have experienced a mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) between 3 months to 10 years ago. Candidates must be fluent in English, not involved in other studies, without epilepsy or severe heart conditions, not pregnant, and free from certain metal implants that affect MRI or TMS procedures.

Inclusion Criteria

You have both a head injury and post-traumatic stress disorder, as determined by specific medical assessments.

I experienced a mild traumatic brain injury between 3 months and 10 years ago.

Exclusion Criteria

You scored less than 85% on a test that checks if you are answering questions honestly, and a specialist thinks you might not be answering accurately.

You have a pacemaker, defibrillator, cochlear implant, nerve stimulator, or metal clips in your head.

I tested positive for opiates without a prescription, or I'm taking more than 200 mg of morphine daily with a prescription.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 30 1-hour treatment sessions of APT and iTBS, conducted 3 times per week for 10 weeks

10 weeks

30 visits (in-person)

Follow-up

Participants are monitored for changes in PTSD symptoms and adaptability using PCL and MPAI assessments

10 weeks

Assessments at baseline, 5 weeks, 10 weeks, and 20 weeks

What Are the Treatments Tested in This Trial?

Interventions

• APT
• iTBS

Trial Overview The study tests the combined effect of attention processing training (APT) with intermittent theta burst stimulation (iTBS), against placebos for each treatment. It aims to assess improvements in attention among those with mTBI plus PTSD and understand changes in their neurocognitive systems.

How Is the Trial Designed?

Group I: real APT+ real iTBS Experimental Treatment 2 Interventions

real APT+ real iTBS included 30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. APT-III is a computer based cognitive training program. iTMS will be applied at 5Hz rate; each burst consists of 3 pulses delivered at 50Hz rate. The bursts are applied for 2s with 8s inter-burst-intervals, for a total of 600 pulses. The total stimulation time per session is approximately 192s (\~ 3 minutes). Participants randomized to active iTBS will receive stimulation at the right dorsolateral prefrontal cortex at 80% active motor threshold .

Group II: placebo APT+ real iTBS Active Control 2 Interventions

30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. Placebo APT-III is a computer based active control cognitive training program. Bursts of TMS pulses will be applied at 5Hz rate; each burst consists of 3 pulses delivered at 50Hz rate. The bursts are applied for 2s with 8s inter-burst-intervals, for a total of 600 pulses. The total stimulation time per session is approximately 192s (\~ 3 minutes). Participants randomized to active iTBS will receive stimulation at the right DLPFC at 80% active motor threshold .

Group III: real APT + placebo iTBS Active Control 2 Interventions

30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. APT-III is a computer based cognitive training program. Participants randomized to placebo iTBS will not receive any iTBS stimulation.

Group IV: placebo APT+ placebo iTBS Active Control 2 Interventions

30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. Placebo APT-III is a computer based active control cognitive training program. Participants randomized to placebo iTBS will not receive any iTBS stimulation.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Theresa Pape

Lead Sponsor

Trials

1

Recruited

200+

Published Research Related to This Trial

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Intermittent theta-burst stimulation (iTBS) shows promise as a targeted treatment for cognitive and psychosocial deficits following traumatic brain injury (TBI), potentially enhancing recovery when combined with behavioral interventions like cognitive rehabilitation and psychotherapy.

This review suggests that iTBS could lead to consistent functional gains in TBI patients, and future research may explore its application in other complex neuropsychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS/iTBS and Cognitive Rehabilitation for Deficits Associated With TBI and PTSD: A Theoretical Framework and Review. Lindsey, A., Ellison, RL., Herrold, AA., et al.[2023]

Intermittent Theta Burst Stimulation (iTBS) was well-tolerated by eight Australian veterans with PTSD, with only mild to moderate side effects reported, such as cranial pain and headaches, which were manageable with analgesics.

Participants showed significant reductions in PTSD and depression symptoms after 20 sessions of iTBS, along with improvements in cognitive functions like working memory and processing speed, suggesting that iTBS could be a promising new treatment for veterans with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring Theta Burst Stimulation for Post-traumatic Stress Disorder in Australian Veterans-A Pilot Study. Nursey, J., Sbisa, A., Knight, H., et al.[2021]

In a study involving 36 multiple sclerosis patients, intermittent theta burst stimulation (iTBS) significantly improved manual dexterity, as shown by faster completion times in the nine-hole peg test and increased performance in the Box and Block Test.

However, iTBS did not have a significant impact on hand motor imagery abilities, indicating that while it can enhance physical tasks, it may not affect cognitive aspects of motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study. Azin, M., Zangiabadi, N., Iranmanesh, F., et al.[2020]

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

A study involving 50 veterans with PTSD showed that intermittent theta-burst stimulation (iTBS) significantly improved social and occupational functioning after 2 weeks, indicating its potential efficacy as a treatment for PTSD.

One month after treatment, iTBS demonstrated significant reductions in both clinician- and self-rated PTSD symptoms, as well as improvements in depression and functioning, suggesting that iTBS could be a promising new approach for managing PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder. Philip, NS., Barredo, J., Aiken, E., et al.[2020]

This study aims to develop and assess a combined intervention of intermittent theta burst stimulation (iTBS) and yoga for military veterans with mild traumatic brain injury (mTBI) and chronic pain, focusing on feasibility and acceptability.

The intervention will be conducted over 6 weeks with 20 participants, and it is expected to provide preliminary evidence of safety and effectiveness in improving quality of life, function, and pain management for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of a Combined Neuromodulation and Yoga Intervention for Mild Traumatic Brain Injury and Chronic Pain: Protocol for an Open-label Pilot Trial. Krese, KA., Donnelly, KZ., Etingen, B., et al.[2023]

In a study involving 46 veterans with PTSD, those who received 4 weeks of active intermittent theta burst stimulation (iTBS) had significantly better long-term outcomes, with a mean relapse time of 296 days compared to 182 days for those who received only 2 weeks of active treatment.

The study suggests that greater exposure to active iTBS is associated with reduced clinical relapse rates and that neuroimaging of brain connectivity may help predict long-term treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder. Petrosino, NJ., Wout-Frank, MV'., Aiken, E., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12098106/

SMART accelerates rate of cognitive gains in service ... SMART is an efficient and effective CR protocol for improving higher-order cognitive abilities in ADSMs with mTBI, achieving comparable outcomes to SCORE in 60 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0003999324011377

Attention Training After Moderate-to-Severe Traumatic ... Overall findings suggest that attentional gains can be made in this sample, irrespective of time since injury, age, and injury severity.

3. academic.oup.com academic.oup.com/milmed/article/189/Supplement_3/568/7735899

Standardizing Attention Process Training-III for a Multisite ... Attention Process Training-III (APT-III) was selected for its strong evidence base, manualized procedures, and computerized program. However, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7726225/

Cognitive Training for Mild Traumatic Brain Injury and ... This randomized controlled trial examined the effectiveness of a 9-h group cognitive training targeting higher-order functions, Strategic Memory Advanced ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7219918/

An Open-Label Feasibility Trial Examining the ... The current study investigated the efficacy of an established cognitive remediation program, Goal Management Training (GMT), in improving cognitive functioning.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12018855/

A New Mobile App to Train Attention Processes in People With ... This tool can be tested to train attention processes after a neurological insult such as traumatic brain injury.

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000210888

Attention Process Training in Neurorehabilitation To evaluate the latest evidence on Attention Process Training (APT) from the past decade across various conditions affecting cognitive function.

8. cdc.gov cdc.gov/heads-up/hcp/clinical-guidance/index.html

Managing Return to Activities | HEADS UP Some policies may require health care professionals to take a training program or provide written clearance as part of the return to play ...

9. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05837676

NCT05837676 | Problem-Solving Training for Concussion Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...