Foundations in Developing Precision Cognitive Restoration

August 27, 2024 updated by: VA Office of Research and Development

Foundational Elements of an Alternate Scientific Approach to Developing Veteran-centric Precision Cognitive Restoration Interventions

This pilot study tests the merits of a unique research approach, transdiagnostic sampling. For Veterans with similar levels of cognitive impairments cause by different types of brain injuries (stroke or traumatic brain injury), this study examines effects of two cognitive restorative treatments. Instead of using the traditional approach to examine treatment effects strictly by cause of brain injury, the transdiagnostic sampling approach recognizes that cause of injury does not drive treatment responsiveness of recovery.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The purpose of this study is to identify the supports and barriers to scalability of Veteran-tailored iTBS and APT across neurologic conditions, with the longer-term goal of providing an empirical basis for the tailoring of a broader range of cognitive rehabilitation strategies to optimize each Veteran's cognitive function in daily life. After Veterans receive standard cognitive rehabilitation, cognitive impairments often persist and if they do make gains there is limited carry-over to daily function. The tenets of precision neurorehabilitation suggest that tailored interventions will optimize gains and carry-over, but precision-tailoring of cognitive rehabilitation will only be possible if researchers develop and test scalable approaches for identifying, organizing, and analyzing the multitude of Veteran-specific variables driving and influencing treatment responsiveness. This project addresses long-standing scientific barriers to understanding treatment responsiveness, particularly study sample heterogeneity and individual variability. The investigators address study sample heterogeneity by linking Veterans, across TBI and ischemic stroke, according to levels of cognitive impairment. The investigators create a cohort of Veterans with a homogeneous level of cognitive impairment, thereby enabling explication of person-centric factors influencing treatment responsiveness and carry-over to daily function. Advancing understanding of the basic study design elements will be achieved by leveraging the knowledge of intermittent Theta Burst Stimulation (iTBS) and iTBS paired with Attention Processing Training exercises (iTBS + APT). iTBS is advantageous as it robustly improves working memory with just one treatment session. These interventions, together, are advantageous as they can each be tailored to a Veteran's unique cognitive challenges and to target the neural site, unique to each Veteran's neuropathology. These two interventions also directly address cognitive deficits, while simultaneously inducing neuroplasticity in neural regions hampered or impaired by neural injury. The investigators will study Veterans with moderately impaired cognition who, after standard cognitive rehabilitation, continue to struggle with daily life requiring assistance with complex instrumental activities of daily living (IADL). Veterans will participate in a series of two within-subject treatment studies, conducted on two separate days, 2-weeks apart. Veterans will be randomly assigned to first receive a single session of Active iTBS or Placebo iTBS and then they will receive APT paired with their assigned iTBS (Active iTBS + APT vs Placebo iTBS + APT). The investigators will test if diagnosis moderates the effects of these interventions on both immediate and persisting change in cognition. For immediate effects, the investigators use a novel testing battery and for persisting gains the investigators use established and feasible neuropsychological tests as well as an established test of cognitive function during IADL. Results will be used to obtain pilot data and examine feasibility in terms of study attrition relative to Veteran fatigue, mood, and Veteran reports of suitability of key aspects of the study design. These findings will be used to develop a future merit within-subject cross-over study examining the over-arching hypothesis that tailored iTBS and APT applied to a transdiagnostic sample and subsequently matched to a Veteran, according to a biotype algorithm, will result in better functional performance of Veteran-valued IADL.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Theresa L Pape, DrPH MA BS
  • Phone Number: 24953 (708) 202-8387
  • Email: theresa.pape@va.gov

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Hines, Illinois, United States, 60141-3030
        • Edward Hines Jr. VA Hospital, Hines, IL

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of TBI or Ischemic Stroke
  • 2-10 years post neurologic event having completed rehabilitation
  • Age 18 - 80 years old
  • Medically stable
  • Fluent in English
  • Moderately impaired cognitive function as defined by AMPS Processing sub-scale measures falling below 1.0 logits
  • Moderately impaired cognitive capacity as defined by having two or more scores falling 1 standard deviation below age normed expectations on: the RBANS index scores, DKEFS Color-Word Trials 3 and 4 scale scores, and/or WAIS-IV Digit Span scaled score

Exclusion Criteria:

  • Have BOTH TBI and Ischemic Stroke
  • Intracranial lesions or hemorrhagic stroke
  • Other primary neurologic diagnosis
  • Any dementia diagnosis
  • Reside in an extended care facility
  • Less than 2 years post TBI or ischemic stroke
  • Anti-epileptic medications for seizure activity
  • Seizure within the past 3 months or active seizure
  • Contraindications to MRI/iTBS
  • Medication changes within 3 months of starting participation
  • Currently receiving therapy services
  • Pregnancy
  • FIM scores for problem solving <3 or >4 OR memory <4 or >5, or changes in FIM scores during screening process
  • Neurostimulants that cannot be safely withdrawn
  • Bilateral ischemic stroke
  • Mild or severe impairments in cognitive capacity or cognitive function
  • CHF, implanted pacemakers or defibrillators, or cochlear implants
  • Questionable test validity as indicated by DOT (E-score 17) or BRIEF (Negativity 6; Infrequency 3; Inconsistency 8)
  • RBANS Total Scale < 70
  • History of/or symptoms of psychotic spectrum disorders (i.e., bipolar, schizophrenia)
  • Persons with alcohol use disorder (AUD) and/or substance use disorder (SUD) diagnoses confirmed by clinical and/or scientific experts

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: intermittent Theta Burst Stimulation
Participants will receive 2 treatments of intermittent Theta Burst Stimulation, each two weeks apart. First session will be iTBS alone, the second session will be combined iTBS with APT (Attention processing training).
Device: intermittent Theta Burst Stimulation
intermittent Theta Burst Stimulation (iTBS) is a type of repetitive transcranial magnetic stimulation (rTMS), which uses short magnetic field pulses applied to the scalp to induce currents in the underlying brain. iTBS will be delivered by the MagVenture MagPROX100 with MagOption Stimulator and MagPro Cool Coil B65 A/P. The MagPro Cool Coil B65 A/P can be switched from active to placebo.
Other Names:
  • iTBS, TMS, rTMS
Placebo Comparator: Placebo intermittent Theta Burst Stimulation
Placebo iTBS participants will not receive any stimulation as the coil will be switched to placebo (P) setting. To maintain double-blind in A and P settings, Veterans and researchers wear headphones connected to a sham noise generator. Participants will receive 2 treatments of placebo intermittent Theta Burst Stimulation, each two weeks apart. First session will be iTBS alone, the second session will be combined placebo iTBS with APT (Attention processing training).
Device: Placebo intermittent Theta Burst Stimulation
The placebo coil magnetic stimulation, but does not actually emit a pulse. The placebo coil looks, sounds and feels like an active iTBS coil. The placebo coil, visually identical to the active coil, provides a slight sensory sensation and discharge noise (i.e. clicking) nearly identical to that of the active coil.
Other Names:
  • Placebo or Sham TMS, iTMS, rTMS

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Streamlined Assessment of Motor and Process Skills (s-APMS) Change 5 timepoints: before and after 1st and 2nd session, then follow up
Time Frame: 5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up
Observational assessment by a trained researcher that measures the performance quality of tasks related to activities of daily living in a natural environment. Examples of activities could include light house work, laundry or meal preparation. The sAMPS assesses the quality of the participant's Activity of Daily Living performance by rating effort, efficiency, safety and independence of motor and processing skill items. The performance of these activities are item-level scores ranging from 1=no problem to 6=inordinate, cannot test. This is an observational test and the research clinician interprets AMPS reports to define and interpret reasons for the person's ineffective ADL performance.
5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span subtest
Time Frame: 5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up
Researcher administered verbal assessment use to measure auditory attention as well as working memory. The researcher verbally presents a sequence of numbers to the participant. The participant is to repeat the sequence back to the researcher. The test is administered in three subtest: Digit span forward, Digit Span Backward, and Digit Span Sequencing. Each subtest is scored with correct minus incorrect responses. The final scoring is completed researcher by raw scores and age.
5 timepoints: week 1 before and after intervention, week 3 before and after intervention, week 5 as follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VA Office of Research and Development

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Theresa L Pape, DrPH MA BS, Edward Hines Jr. VA Hospital, Hines, IL

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 24, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 12, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 11, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 29, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • N3751-P

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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