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

Trial Summary

What is the purpose of this trial?

This study will determine (i) the magnitude of immediate and sustained effects of a current clinical standard interactive computer attention processing training (APT) when combined with intermittent theta burst stimulation (iTBS), a type of repetitive transcranial magnetic stimulation and (ii) determine how APT + iTBS changes the neurocognitive system of attention in individuals with persistent attention deficits related to mTBI +/- PTSD.

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.

What data supports the effectiveness of the treatment APT, iTBS, Intermittent Theta Burst Stimulation, iTBS Therapy, Theta Burst Stimulation for Concussion and PTSD?

Research shows that intermittent theta burst stimulation (iTBS) can improve symptoms of PTSD and depression, and when combined with other therapies, it may enhance cognitive recovery in traumatic brain injury (TBI). Studies have found that iTBS is effective in improving clinical outcomes for PTSD, with benefits lasting up to a year. ^{1 2 3 4 5}

Is theta burst stimulation (TBS) safe for humans?

Theta burst stimulation (TBS), including intermittent TBS (iTBS), has been generally found to be safe in humans, with most adverse events being mild and occurring in about 5% of subjects. However, there is a theoretical risk of seizures, so it should be used with caution, and more research is needed to fully understand its safety profile. ^{1 2 4 6 7}

How is the treatment for concussion and PTSD using iTBS different from other treatments?

The treatment using intermittent theta burst stimulation (iTBS) is unique because it is a non-invasive method that directly stimulates specific brain areas to enhance cognitive and functional recovery, and it can be combined with other therapies like cognitive rehabilitation to boost their effectiveness. ^{1 2 5 8 9}

Research Team

Theresa LB Pape, Dr.PH

Principal Investigator

Northwestern University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

rTMS/iTBS and Cognitive Rehabilitation for Deficits Associated With TBI and PTSD: A Theoretical Framework and Review. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Exploring Theta Burst Stimulation for Post-traumatic Stress Disorder in Australian Veterans-A Pilot Study. [2021]

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

Theta-Burst Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder. [2020]

4. England pubmed.ncbi.nlm.nih.gov

One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder. [2021]

5. Estonia 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. [2020]

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

7. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

8. Canada 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. [2023]

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

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. [2016]