Neuromodulation + Cognitive Training for Traumatic Brain Injury

(CONNECT-TBI Trial)

Recruiting at 4 trial locations

Overseen By Davin k Quinn, MD, FACLP

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of New Mexico

Must be taking: Psychotropic medications

Disqualifiers: Neurological disease, Seizures, Psychosis, others

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

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods to improve thinking skills in Veterans with mild traumatic brain injury (mTBI) who continue to struggle with focus or memory. It examines the combination of Attention Process Training, a cognitive training program, with various types of brain stimulation to determine the most effective approach. Veterans who may qualify for this trial are those who sustained a mild brain injury between 3 months and 5 years ago and experience ongoing cognitive difficulties. As an unphased trial, it provides Veterans the chance to explore innovative treatments that could enhance cognitive recovery.

Will I have to stop taking my current medications?

The trial requires that participants have been on stable doses of any psychotropic medications for the past 2 months, so you won't need to stop taking them if they have been stable.

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

Research shows that both repetitive transcranial magnetic stimulation (rTMS) and high-definition transcranial direct current stimulation (HD-tDCS) have undergone safety testing in people with traumatic brain injuries.

For rTMS, studies have found it generally well-tolerated. Safety checks revealed no serious side effects in patients with brain injuries. Some individuals might experience mild side effects like headaches or scalp discomfort, but these usually resolve quickly.

Research on HD-tDCS also suggests safety for people with brain injuries. One study found that participants using HD-tDCS showed better cognitive performance without serious side effects. Mild side effects, such as tingling on the scalp, can occur but are not harmful.

Both treatments have been studied in other trials and are considered safe for humans. However, participants should discuss any concerns with their healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these trial treatments because they combine neuromodulation techniques with cognitive training to tackle traumatic brain injury (TBI) in innovative ways. Unlike standard therapies that often focus solely on cognitive rehabilitation, the trial explores the use of repetitive Transcranial Magnetic Stimulation (rTMS) and High-Definition transcranial Direct Current Stimulation (HD-tDCS) to enhance brain plasticity and recovery. These neuromodulation methods deliver non-invasive brain stimulation, potentially offering faster and more effective recovery by directly targeting brain regions involved in attention and cognitive processes. This approach represents a promising shift towards integrating brain stimulation with cognitive training to improve outcomes for TBI patients.

What evidence suggests that this trial's treatments could be effective for cognitive control deficits in complex mTBI?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve memory and thinking skills in people with traumatic brain injury (TBI). In this trial, some participants will receive active rTMS combined with cognitive exercises like Attention Process Training (APT-3), which studies indicate may enhance mental control. Additionally, high-definition transcranial direct current stimulation (HD-tDCS) has boosted thinking abilities in those with long-term TBI. Other participants in this trial will receive active HD-tDCS with APT-3. Some research also suggests that HD-tDCS can improve language skills for weeks after treatment. Overall, early findings are promising for using rTMS and HD-tDCS with APT-3 to address thinking problems from mild TBI. ^{1 2 6 7 8}

Who Is on the Research Team?

Davin Quinn, MD

Principal Investigator

University of New Mexico

Are You a Good Fit for This Trial?

This trial is for Veterans aged 18-59 who've had a mild traumatic brain injury (TBI) with specific cognitive symptoms, and have been stable on any psychotropic meds for 2 months. They must not be pregnant, involved in TBI litigation, or have certain medical conditions like psychosis or recent substance dependence.

Inclusion Criteria

You had an injury 3 months to 5 years ago.

I had memory loss for less than a day after my injury.

Fluent in English

Exclusion Criteria

You had a Glasgow coma scale (GCS) score that was too low or too high when you were admitted to the emergency department.

Appointment of a legal representative

You are currently involved in a lawsuit related to traumatic brain injury.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Testing

Participants undergo demographic, neuropsychological, behavioral, and quality of life testing, as well as MRI scanning

1 visit

1 visit (in-person)

Treatment

Participants receive 16 sessions of APT-3 with concurrent rTMS, HD-tDCS, or sham stimulation

4 weeks

16 visits (in-person)

Post-treatment

Repeat of baseline tests including neuropsychological testing, symptom assessment, and MRI

1 visit

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment at 3 and 6 months

6 months

2 visits (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Attention Process Training
• HD-tDCS
• rTMS

Trial Overview The CONNECT-TBI Trial tests whether Attention Process Training combined with either rTMS (magnetic stimulation), HD-tDCS (electrical brain stimulation), or sham treatment improves cognitive function in those with complex mTBI. Participants will undergo extensive testing before and after the treatments to measure effectiveness.

How Is the Trial Designed?

Group I: Active rTMS with Attention Process Training Active Control 2 Interventions

Subjects in this arm will receive active rTMS and then complete the assigned Attention Process Training battery immediately following active rTMS.

Group II: Active HD-tDCS with Attention Process Training Active Control 2 Interventions

Subjects in this arm will receive active HD-tDCS and complete the assigned Attention Process Training battery during active HD-tDCS.

Group III: Sham rTMS with Attention Process Training Placebo Group 2 Interventions

Subjects in this sham arm will not receive any active stimulation and will only complete Attention Process Training immediately following sham rTMS.

Group IV: Sham HD-tDCS with Attention Process Training Placebo Group 2 Interventions

Subjects in this sham arm will not receive any active stimulation and will only complete Attention Process Training during sham HD-tDCS.

Who Is Running the Clinical Trial?

University of New Mexico

Lead Sponsor

Trials

393

Recruited

3,526,000+

The Mind Research Network

Collaborator

Trials

27

Recruited

2,300+

New Mexico VA Healthcare System

Collaborator

Trials

9

Recruited

1,100+

Minneapolis Veterans Affairs Medical Center

Collaborator

Trials

77

Recruited

355,000+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

New Mexico Veterans Affairs Health Care System

Collaborator

Trials

1

Recruited

110+

The United States Department of Defense USAMRDC

Collaborator

Trials

1

Recruited

110+

Published Research Related to This Trial

A case study of a Canadian soldier with severe traumatic brain injury showed that combining physical therapy with translingual neurostimulation (PT + TLNS) led to significant recovery of motor function even 14 years after the injury.

In addition to motor improvements, PT + TLNS was associated with enhanced cognitive functions, such as increased attention and processing speed, and a reduction in PTSD symptoms, highlighting the potential of non-invasive neuromodulation in cognitive rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Vital Signs Detect Cognitive Improvements During Combined Physical Therapy and Neuromodulation in Rehabilitation From Severe Traumatic Brain Injury: A Case Report. Fickling, SD., Greene, T., Greene, D., et al.[2023]

Attention Process Training (APT) significantly improved specific cognitive process skills in patients with acquired brain injury compared to Activity-based Attention Training (ABAT), with large effect sizes in areas like Mental Energy and Temporal Organization.

Both APT and ABAT led to significant improvements in overall activity and satisfaction in daily tasks, indicating that while APT may enhance cognitive skills more effectively, both interventions are beneficial for enhancing participation in daily life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of attention process training and activity-based attention training after acquired brain injury: A randomized controlled study. Sargénius Landahl, K., Schult, ML., Borg, K., et al.[2022]

Individualized strategy training significantly improved attention in three participants with severe traumatic brain injury (TBI), showing better outcomes than computer-based training (APT-3) alone, particularly in processing speed and task performance.

The study emphasizes the importance of tailored rehabilitation approaches for attention deficits post-TBI, as participants exhibited varying needs and responses to different training methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive training approaches to remediate attention and executive dysfunction after traumatic brain injury: A single-case series. Dymowski, AR., Ponsford, JL., Willmott, C.[2017]

A study involving three individuals with mild traumatic brain injury (MTBI) showed that a 10-week cognitive retraining program (Attention Process Training-II) significantly improved their attention and performance speed.

The cognitive improvements were maintained for at least 6 weeks after the training ended, suggesting that the APT-II program can provide lasting benefits for individuals with attention difficulties following MTBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rehabilitation of attention in individuals with mild traumatic brain injury, using the APT-II programme. Palmese, CA., Raskin, SA.[2022]

Attention Process Training (APT) effectively improved attention deficits in four brain-injured individuals over 5 to 10 weeks of intensive cognitive remediation, demonstrating significant gains in attention for all subjects.

The study suggests that focusing specifically on attention training can lead to improvements in attention without affecting other cognitive functions, like visual processing, highlighting the benefits of a targeted rehabilitation approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of an attention-training program. Sohlberg, MM., Mateer, CA.[2015]

A study involving 30 traumatic brain injury (TBI) patients showed that non-immersive virtual reality-based attention training significantly improved cognitive functions and mood compared to conventional training methods.

The virtual reality training led to notable improvements in global cognitive status, attention processes, and reduced depression symptoms, indicating its potential as an effective rehabilitation tool for TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Non-Immersive Virtual Reality Improve Attention Processes in Severe Traumatic Brain Injury? Encouraging Data from a Pilot Study. De Luca, R., Bonanno, M., Rifici, C., et al.[2023]

In a study of 78 stroke survivors, attention process training (APT) significantly improved attention deficits compared to standard care alone, indicating its effectiveness in stroke rehabilitation.

While APT showed a notable improvement in the primary attention measure, other broader outcomes did not show significant differences, suggesting that APT specifically targets attention deficits rather than overall cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing attention deficits after stroke using attention process training: a randomized controlled trial. Barker-Collo, SL., Feigin, VL., Lawes, CM., et al.[2022]

In a study involving 71 adults with traumatic brain injury, the combination of Memory and Attention Adaptation Training (MAAT) with methylphenidate (MPH) showed significant improvements in cognitive functions such as word-list learning and nonverbal learning compared to other treatment combinations.

The results indicate that MAAT, especially when paired with MPH, is effective in enhancing attention, episodic memory, and executive functioning in individuals experiencing persistent cognitive issues after TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial. McDonald, BC., Flashman, LA., Arciniegas, DB., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12104519/

Standardizing Attention Process Training-III for a Multisite ... It combines APT-III with noninvasive neuromodulation—repetitive transcranial magnetic stimulation, high-definition transcranial direct current ...

2. apps.dtic.mil apps.dtic.mil/sti/trecms/pdf/AD1126832.pdf

High-Definition Transcranial Direct Current Stimulation (HD-tDCS ... Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1388245722008690

High-definition transcranial direct current stimulation ... High Definition transcranial Direct Current Stimulation (HD-tDCS) has been shown to improve cognitive performance in individuals with chronic traumatic brain ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04599764

High Definition Transcranial Direct Current Stimulation (HD ... Each participant would be treated for 10 days in two weeks by HD-tDCS. Before the tDCS, a series of cognitive assessments and neuropsychological tests were ...

5. journals.sagepub.com journals.sagepub.com/doi/full/10.1089/neu.2018.6331

High-Definition Transcranial Direct Current Stimulation to ... Improvements in verbal retrieval processes were observed up to 8 weeks post-treatment. Thus, potential dysfunction to verbal retrieval circuitry in TBI appears ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06228872

"Cognitive Rehabilitation With Direct Current Transcranial ... Transcranial direct current stimulation of the left prefrontal cortex improves attention in patients with traumatic brain injury: a pilot study. J Rehabil ...

7. apps.dtic.mil apps.dtic.mil/sti/trecms/pdf/AD1199613.pdf

High-Definition Transcranial Direct Current Stimulation (HD ... The intervention is 10 days of anodal HD-tDCS to the left dorsolateral prefrontal cortex, paired with vision therapy and cognitive training.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10545365/

High Definition transcranial Direct Current Stimulation ... High Definition transcranial Direct Current Stimulation (HD-tDCS) has been shown to improve cognitive performance in individuals with chronic traumatic brain ...