Neuromodulation + Cognitive Training for Traumatic Brain Injury

(CONNECT-TBI Trial)

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by Davin Quinn, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of New Mexico

Must be taking: Psychotropic medications

Disqualifiers: Neurological disease, Seizures, Psychosis, others

No Placebo Group

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.

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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.

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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.

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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.

Trial 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)

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

The University of Minnesota Minneapolis, MN

The University of New Mexico Albuquerque, NM

The Mind Research Network Albuquerque, NM

Minneapolis Veterans Affairs Medical Center Minneapolis, MN

More Trial Locations

Who Is Running the Clinical Trial?

University of New Mexico Lead Sponsor

The Mind Research Network Collaborator

New Mexico VA Healthcare System Collaborator

Minneapolis Veterans Affairs Medical Center Collaborator

University of Minnesota Collaborator

New Mexico Veterans Affairs Health Care System Collaborator

The United States Department of Defense USAMRDC Collaborator

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] Traumatic brain injury (TBI) is a prevalent cause of cognitive impairments and dysfunctions and affects over 2 million individuals each year. Mild traumatic brain injury (MTBI) is generally defined by a brief loss of consciousness, and post-traumatic amnesia that lasts for less than 24 hours. One region of the brain that is likely affected in patients with MTBI is the pre-frontal cortex. This region mediates several functions, including those required for adequate attention. Three individuals, diagnosed with MTBI and difficulties with attention, volunteered to participate in the study. Individuals were presented with 10 weeks of cognitive retraining with the Attention Process Training-II (APT-II) programme, followed by 6 or 7 weeks of educational and applicational programmes. Cognitive tests were administered both pre- and post-training to assess the effectiveness of the programme. Analysis of the results showed that the APT-II programme improved attention and performance speed in each of the three individuals. In addition, any rehabilitated cognitive skills remained stable in each individual in the absence of the rehabilitation programme for at least 6 weeks.

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

Reducing attention deficits after stroke using attention process training: a randomized controlled trial. [2022] Impaired attention contributes to poor stroke outcomes. Attention process training (APT) reduces attention deficits after traumatic brain injury. There was no evidence for effectiveness of APT in stroke patients. This trial evaluated effectiveness of APT in improving attention and broader outcomes in stroke survivors 6 months after stroke.

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] Attentional deficits are common following traumatic brain injury (TBI) and interfere with daily functioning. This study employed a single-case design to examine the effects of individualised strategy training on attention beyond the effects of computerised training using Attention Process Training 3 (APT-3), and to examine the participants' subjective experience of these approaches. An ABCA (baseline, APT-3, strategy training, follow-up) design was repeated across three participants with severe TBI. Outcomes were measured on alternate versions of the oral Symbol Digit Modalities Test (SDMT) and cancellation tasks; generalisation with the Test of Everyday Attention (TEA) and self and significant other (SO) ratings on the Rating Scale of Attentional Behaviour (RSAB); and participant experiences with semi-structured interviews. Planned Tau-U analyses revealed improvements in speed of processing on the SDMT and the automatic condition of the cancellation task after APT-3 and at follow-up, but with most improvement after strategy training. Limited generalisation was evident on TEA subtests and self-RSAB ratings. SO-RSAB ratings were mixed after APT-3, but demonstrated improvement after strategy training. Variability in attentional deficits and everyday attentional requirements between patients required individualised goals and approaches to rehabilitation. This study highlights the need for individualised rehabilitation of attention to improve everyday functioning after TBI.

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] To compare the effects of 2 interventions for attention deficits in people with acquired brain injury, Attention Process Training (APT) and Activity--based Attention Training (ABAT), on activity and participation.

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

Effectiveness of an attention-training program. [2015] Attention Process Training (APT), a hierarchical, multilevel treatment program, was designed to remediate attention deficits in brain-injured persons. The program incorporates current theories in the experimental attention literature. Four brain-injured subjects, varying widely in both etiology of injury and time post onset, underwent intensive cognitive remediation including 5 to 10 weeks of specific attention training. Results are displayed using a single subject multiple baseline across behaviors design. All four subjects demonstrated significant gains in attention following the initiation of attention training. Remediation of another cognitive function (visual processing) was not associated with alterations in attention behavior. The merits of a process-specific approach to cognitive rehabilitation are discussed.

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] Using a longitudinal case study design, we have tracked the recovery of motor function following severe traumatic brain injury (TBI) through a multimodal neuroimaging approach. In 2006, Canadian Soldier Captain (retired) Trevor Greene (TG) was attacked with an axe to the head while on tour in Afghanistan. TG continues intensive daily rehabilitation, which recently included the integration of physical therapy (PT) with neuromodulation using translingual neurostimulation (TLNS) to facilitate neuroplasticity. Recent findings with PT + TLNS demonstrated that recovery of motor function occurred beyond conventional time limits, currently extending past 14-years post-injury. To investigate whether PT + TLNS similarly resulted in associated cognitive function improvements, we examined event-related potentials (ERPs) with the brain vital signs framework. In parallel with motor function improvements, brain vital signs detected significant increases in basic attention (as measured by P300 response amplitude) and cognitive processing (as measured by contextual N400 response amplitude). These objective cognitive improvements corresponded with TG's self-reported improvements, including a noteworthy and consistent reduction in ongoing symptoms of post-traumatic stress disorder (PTSD). The findings provide valuable insight into the potential importance of non-invasive neuromodulation in cognitive rehabilitation, in addition to initial indications for physical rehabilitation.

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] The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (PABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI.

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] Traumatic brain injury (TBI) is a sudden injury that causes damage to the brain. Rehabilitation therapies include specific training, such as attention process training (APT) programs using either standard or innovative approaches. The aim of this study is to evaluate the effects of a non-immersive virtual reality-based attention training to stimulate attention processes and mood in TBI patients. Thirty subjects with TBI were enrolled at the Neurorehabilitation Unit of the IRCCS Neurolesi Center and divided into either the Conventional Attention Process Training Group (C_APT: n = 15) or the Virtual-Based Attention Processes Training Group (VB_APT: n = 15), treated with the Virtual Reality Rehabilitation System (VRRS-Evo). All of the patients were evaluated with a specific psychometric battery before (T0) and after the end (T1) of each program. We found statistically significant differences between the two groups, in particular concerning global cognitive status (p