Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Improvements in Cognitive Skills From Traumatic Brain Injury Using Dynamic Visual Attention Training

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03655782
Recruitment Status : Not yet recruiting
First Posted : August 31, 2018
Last Update Posted : July 25, 2019
Sponsor:
Collaborators:
University of California, San Diego
University of South Alabama
Information provided by (Responsible Party):
Perception Dynamics Institute

Brief Summary:
The proposed study tests the feasibility (Phase I) and efficacy (Phase II) of PATH neurotraining to improve working memory and attention in mTBI patients rapidly and effectively to provide clinical testing of a therapeutic training for the treatment of neurological disorders caused by a concussion. This study will contribute to the fundamental knowledge of how to remediate concussions from a mTBI to enhance the health, lengthen the life and reduce the disabilities that result from a mTBI.

Condition or disease Intervention/treatment Phase
MTBI - Mild Traumatic Brain Injury Behavioral: PATH neurotraining Behavioral: Orientation Discrimination Not Applicable

Detailed Description:
This study will provide clinical testing of therapeutic training for the treatment of neurological disorders caused by a concussion. We will extend previous results from a pilot study of 4 mTBI subjects (Lawton & Huang, 2019) to a much larger sample of mTBI subjects. During Phase II we will determine whether these results are sustained over time. The proposed study tests the feasibility (Phase I) and efficacy (Phase II) of PATH neurotraining to improve working memory (primary outcome) and attention (secondary outcome) in mTBI subjects rapidly and effectively. This study will compare PATH training (C.3.1), presenting dim gray patterns moving left or right to activate the dorsal stream (Ungerleider & Mishkin, 1982; Livingstone & Hubel, 1988; Kaplan & Shapley, 1986), with sham training (C.3.2), presenting high contrast colored stationary patterns tilted left or right to activate the parvocells in the ventral stream. We predict that sham training does not improve attention and working memory in mTBI. Since PATH training must be followed by cognitive exercises to improve cognitive function (Lawton, 2015, 2016), having subjects drive to and from the test site, when possible, provides cognitive exercises that facilitate improving cognitive function in mTBI. MEG recordings (Huang et al., 2014, 2016, 2018) before and after training will provide a biomarker to determine whether PATH training improves the function of the dorsal, attention, and working memory networks more than found after a sham treatment. MEG recordings will also be used to determine whether PATH training strengthens coupled theta/ gamma activity, and/or alpha/ gamma activity. To increase its commercialization ability, PATH neurotraining must be shown to improve brain function using a biomarker, as stated by neurologists and therapists in letters of support. During Phase II the impact of PATH neurotraining will be evaluated on a much larger sample of mTBI subjects and will be offered to mTBI subjects after they finish the sham training. Whether cognitive improvements are sustained over time will be evaluated by measuring whether mTBI subjects improve on neuropsychological tests of cognitive function 3 and 6 months after training.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 153 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: During Phase I and Phase II of this study, we will show that working memory and attention improve more in TBI patients after neurotraining that improves sensory and processing speed functions, improving the motion working range (PATH), more than after sham training that activates a different visual pathway to show its feasibility and efficacy. MEG brain imaging will be used to show that PATH neurotraining improves the function of the dorsal, attention, and working memory networks (e.g., PPC, DLPFC and ACC/PCC areas), reducing over recruitment, more than found after sham training.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: Staff will not be told whether the subject was in the treatment or control group. The statistician will not know which group was the treatment group and which was the control group.
Primary Purpose: Treatment
Official Title: Improvements in Cognitive Skills From Traumatic Brain Injury Using Dynamic Visual Attention Training
Estimated Study Start Date : January 2, 2020
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : July 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PATH neurotraining
Subject looks at computer screen to determine whether dim gray stripes in fish-shaped window move left or right relative to stationary background stripes. The subject reports which way center stripes move by pushing left or right arrow key, receiving brief tone if incorrect. Program adaptively changes contrast of test pattern in order to keep subject at 79% correct. There are levels of difficulty introduced by making the background pattern more similar to that in fish, by increasing pattern's complexity level, and by increasing number of directions of movement from one to two directions of motion. Intervention will be trained for one training cycle, between 10-20 minutes, 3 times each week for 12 weeks.
Behavioral: PATH neurotraining
Improve visual timing and sensitivity in the dorsal stream. The mTBI subject will sit 57 cm in front of a computer monitor. During the presentation, the bars in the 'fish-shaped' window in the center of the screen formed by a sinusoidal grating, move left or right very briefly. When the screen goes blank, the subject reports which way the center pattern moved by pushing the left or right arrow key. A brief tone is presented after incorrect responses. The program adaptively changes the contrast of the test pattern so that the subject detects motion at lowest contrast possible. A sequence of patterns in each training cycle that are designed to optimally activate magnocellular neurons are shown to the subject. There are two programs, the first measures the contrast needed to see one direction of movement, and the second program measures the contrast needed to see two directions of movement, requiring memory.
Other Name: PATH to Insight

Sham Comparator: Orientation Discrimination training
The sham treatment will be Orientation Discrimination training that is identical to PATH training except instead of low contrast sinewave gratings moving left or right, 100% contrast stationary test and background sinewave gratings are used, both red, green, and black and white gratings, see patterns in Fig. 4 below. These patterns are randomly oriented left or right, at decreasing tilt angles as the test grating's orientation is identified correctly. These patterns only activate parvocells in ventral pathways (Ungerleider & Mishkin, 1982; Kaplan & Shapley, 1986) instead of activating dorsal pathways, the key component of PATH neurotraining. Therefore, this task does not speed up the brain's visual timing, which is a function of the dorsal stream. For the Orientation Discrimination task, the subject pushes the left arrow key when the test pattern is tilted left and the right arrow key when pattern is tilted right. Otherwise the two training tasks use the same paradigm.
Behavioral: Orientation Discrimination
The sham treatment will be Orientation Discrimination training that is identical to PATH training except instead of low contrast sinewave gratings moving left or right, 100% contrast stationary test and background sinewave gratings are used, both red, green, and black and white gratings. These patterns are randomly oriented left or right, at decreasing tilt angles as the test grating's orientation is identified correctly. These patterns only activate parvocells in ventral pathways (Ungerleider & Mishkin, 1982; Kaplan & Shapley, 1986) instead of activating dorsal pathways, the key components of PATH neurotraining. Therefore, this task does not speed up the brain's visual timing, which is a function of the dorsal stream. For the Orientation Discrimination task, the subject pushes the left arrow key when the test pattern is tilted left and the right arrow key when pattern is tilted right. Otherwise the two training tasks use the same paradigm.
Other Name: sham training




Primary Outcome Measures :
  1. Change in Visual Working Memory [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training and 3 and 6 months after training. ]
    The Test of Information Processing Skills Visual Working Memory Standardized Percentile Rank that goes from < 1% to > 99%


Secondary Outcome Measures :
  1. Change in Attention [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training and 3 and 6 months after training. ]
    DKEFS Color-Word Interference Test Standardized Percentile Rank for Inhibition subtest going from 0.5% to 99.9%

  2. Change in Cognitive Flexibility [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training and 3 and 6 months after training. ]
    DKEFS Color-Word Interference Test standardized scores for Standardized Percentile Rank for Inhibition Switching subtest going from 0.5% to 99.9%

  3. Change in Auditory Working Memory [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training and 3 and 6 months after training. ]
    The WAIS Working Memory Index Standardized Percentile Rank that goes from < 0.1% to > 99.9%

  4. Change in Processing Speed [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training and 3 and 6 months after training. ]
    WAIS Processing Speed Index Standardized Percentile Rank that goes from < 0.1% to > 99.9%

  5. Change in Reading Speed [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training and 3 and 6 months after training. ]
    Number of words/minute subject can read 6 words of text from interesting story using computer-based program.

  6. Change in DLPFC Function [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training ]
    Using the total covariance matrix, voxel-wise MEG source magnitude images that cover the whole brain will be obtained for each subject, and each frequency band, following the Fast-VESTAL procedure, measuring time-locked signals during a working memory N-back task to evaluate improvements in brain function in DLPFC (working memory).

  7. Change in ACC Function [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training ]
    Using the total covariance matrix, voxel-wise MEG source magnitude images that cover the whole brain will be obtained for each subject, and each frequency band, following the Fast-VESTAL procedure, measuring time-locked signals during a working memory N-back task to evaluate improvements in brain function in ACC (attention network).

  8. Change in Precuneus/PCC [ Time Frame: Immediately before and after 12 weeks of PATH training or sham training ]
    Using the total covariance matrix, voxel-wise MEG source magnitude images that cover the whole brain will be obtained for each subject, and each frequency band, following the Fast-VESTAL procedure, measuring time-locked signals during a working memory N-back task to evaluate improvements in brain function in Precuneus/PCC (attention network).


Other Outcome Measures:
  1. Blinding Assessments [ Time Frame: Immediately after 12 weeks of PATH training or sham training ]
    Use the standardized blinding procedure and analysis suggested by Band et al (2010). Joint Estimation of Treatment and Placebo Effects in Clinical Trials with Longitudinal Blinding Assessments. A questionnaire will be administered to all participants, as well as to research assistants who are administering the task. The items will be: (1) three response categories for treatment guess: 'New treatment', 'Placebo (or control)', or 'Don't know (DK)', and (2) five response categories: 'Strongly believe the treatment is new treatment', 'Somewhat believe the treatment is new treatment', 'Somewhat believe the treatment is placebo', 'Strongly believe the treatment is placebo', or 'DK'. We may re-ask those who answered DK initially to make their best guess regarding their assignment. These data can then be used in a joint statistical model to estimate and isolate the relative effect of patient and experimenter effects on treatment efficacy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

A patient with a mTBI who has had a traumatically induced physiologic disruption of brain function will be referred by neurologists Drs. Lobatz and Ho who have made a diagnosis of mTBI, which includes one or more of the following (Marshall et al., 2012):

  1. any loss of consciousness from 5- 30 min (not longer than 30 min),
  2. any loss of memory for events immediately before or after the accident for as much as 24 hours,
  3. any alteration of mental state at the time of the accident (e.g. feeling dazed, disoriented, or confused),
  4. after 30 minutes, Glasgow Coma Scale of 13-15 (not lower or is considered more severe than a mild TBI),
  5. post-traumatic amnesia less than 24 hours,
  6. a score of 19-25 on the Montreal Cognitive Assessment (MoCA) screening test, and
  7. focal neurologic deficits that might/might not be transient.

For this study, the following criteria will be utilized:

Inclusion Criteria:

  1. Diagnosis of mTBI,
  2. between the ages of 18 to 55 years, when development and aging are not factors,
  3. agrees to complete the study after hearing the time commitment involved,
  4. has corrected 20/20 visual acuity, so can do PATH training (dim gray stripes),
  5. reads English fluently, so can follow instructions,
  6. can complete the PATH neurotraining task, by pushing the left or right arrow key on the computer, and
  7. can drive to the test site, so do not have major functional issues in cognition.

Exclusion Criteria:

  1. mTBI occurred less than 3 months earlier,
  2. post-traumatic amnesia longer than 24 hours,
  3. diagnosis of epilepsy or seizure disorder in last 12 months,
  4. diagnosis of major depressive disorder or severe anxiety,
  5. answers 'Yes' to any of the questions on the Columbia Suicide Severity Rating Scale,
  6. had a stroke or metabolic derangements causing cognitive impairments, ie. alcohol or substance abuse,
  7. has extensive metal dental hardware (e.g., braces and large metal dentures; fillings are acceptable) or other metal objects in head, neck, or face areas that cause artifacts in MEG data, and are not removable during pre-processing, and
  8. has claustrophobia since MEG scanner is in small enclosed space.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03655782


Contacts
Layout table for location contacts
Contact: Teri Lawton, Ph.D. 310-903-6009 tlawton@pathtoreading.com
Contact: Ming-Xiong Huang, Ph.D.

Locations
Layout table for location information
United States, California
Pacific Center for Neurological Disease Neuroscience Research Institute Not yet recruiting
Poway, California, United States, 92064
Contact: Gilbert Ho, M.D.    858-674-1289    info@pcndneurology.com   
Contact: Alysha Ali, H.S.    714-747-9388    aali@pcndneurology.com   
University of California at San Diego Not yet recruiting
San Diego, California, United States, 92121
Contact: Ming-Xiong Huang, Ph.D.         
Contact: AnneMarie Angeles, B.S.         
Perception Dynamics Institute Not yet recruiting
Solana Beach, California, United States, 92075
Contact: Teri Lawton, Ph.D.    310-903-6009    tlawton@pathtoreading.com   
Contact: Ming-Xiong Huang, Ph.D.       mxhuang@ucsd.edu   
Sub-Investigator: Ming-Xiong Huang, Ph.D.         
Sponsors and Collaborators
Perception Dynamics Institute
University of California, San Diego
University of South Alabama
Investigators
Layout table for investigator information
Principal Investigator: Teri Lawton, Ph.D. Perception Dynamics Institute

Layout table for additonal information
Responsible Party: Perception Dynamics Institute
ClinicalTrials.gov Identifier: NCT03655782     History of Changes
Other Study ID Numbers: PerceptionDI
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: July 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After completion of the study, deidentified data will be made available to qualified outside investigators following NIH Data Sharing guidelines; none of the data will be considered proprietary. Most of the data for this study will be collected through standardized tests of attention, processing speed, and working memory to be administered by the staff on this project
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: September 2024 for 10 years.
Access Criteria: Qualified investigator

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Injuries
Brain Injuries, Traumatic
Brain Concussion
Wounds and Injuries
Brain Diseases
Craniocerebral Trauma
Trauma, Nervous System
Head Injuries, Closed
Wounds, Nonpenetrating
Central Nervous System Diseases
Nervous System Diseases