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

Trial Summary

What is the purpose of this trial?

The CONNECT-TBI Trial aims to develop safe, effective treatments for complex mTBI that improve cognitive functioning. Based on the compelling preliminary data generated by our study team, the objective of this study is to conduct a randomized, double-blinded, sham-controlled Phase II clinical trial of APT-3 combined with rTMS, HD-tDCS, or sham to treat cognitive control deficits in Veterans with complex mTBI and PPCS. At the Baseline Visit, participants will undergo demographic, neuropsychological, behavioral, and quality of life testing. They will also undergo structural MRI to permit modeling of their brain, resting/task-related fMRI to identify the CCN, and pseudocontinuous arterial spin labeling (pCASL) and diffusion tensor imaging (DTI) to assess for other pathologies. They will then be randomized to 16 sessions of APT-3 with concurrent rTMS, HD-tDCS, or sham stimulation delivered to the unique functional left dorsolateral prefrontal cortex (DLPFC), a primary node of the CCN. Lastly, they will repeat all baseline tests, and report on 3- and 6-month recovery levels to establish longevity and stability of subjective benefit. Given that this individualization protocol has never been attempted for cognitive rehabilitation in military mTBI, we expect this trial will generate useful effect sizes for HD-tDCS and rTMS to be used for powering the next step, a Phase III multi-center trial.

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.

What data supports the effectiveness of the treatment Neuromodulation + Cognitive Training for Traumatic Brain Injury?

Research shows that Attention Process Training (APT) can improve attention in individuals with brain injuries, including traumatic brain injury (TBI). Studies have demonstrated significant gains in attention and performance speed after using APT, with improvements remaining stable even after the training ended. ^{1 2 3 4 5}

Is Attention Process Training (APT) safe for humans?

The research articles provided do not contain specific safety data for Attention Process Training (APT) or related neuromodulation techniques, but they do not report any adverse effects, suggesting it may be generally safe for humans. ^{1 2 3 4 5}

How is the Attention Process Training-3 treatment different from other treatments for traumatic brain injury?

Attention Process Training-3 (APT-3) is unique because it combines cognitive training with neuromodulation, which uses non-invasive techniques to stimulate the brain and enhance neuroplasticity (the brain's ability to reorganize itself). This approach is different from standard treatments that may not integrate these elements, potentially leading to improvements in attention and cognitive processing beyond conventional methods. ^{1 5 6 7 8}

Research Team

Davin Quinn, MD

Principal Investigator

University of New Mexico

Eligibility Criteria

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.

My gender does not affect my eligibility for this trial.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Reducing attention deficits after stroke using attention process training: a randomized controlled trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Cognitive training approaches to remediate attention and executive dysfunction after traumatic brain injury: A single-case series. [2017]

4. Sweden pubmed.ncbi.nlm.nih.gov

Comparison of attention process training and activity-based attention training after acquired brain injury: A randomized controlled study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of an attention-training program. [2015]

6. Switzerland 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. [2023]

7. England 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. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Does Non-Immersive Virtual Reality Improve Attention Processes in Severe Traumatic Brain Injury? Encouraging Data from a Pilot Study. [2023]