Neurotechnology Following Traumatic Brain Injury (Cereset)

• ClinicalTrials.gov Identifier: NCT03649958
• Recruitment Status: Recruiting
• First Posted: August 28, 2018
• Last Update Posted: April 7, 2022
• Sponsor: Brain State Technologies, LLC
• Collaborators: Uniformed Services University of the Health Sciences; Womack Army Medical Center
• Information provided by (Responsible Party): Brain State Technologies, LLC

Study Description

Brief Summary:

This two-part study seeks to improve symptoms such as pain and sleep problems after concussion, or mild traumatic brain injury (mTBI).

Study I evaluates symptoms of mTBI through a series of 10 office sessions in which musical tones are echoed, or mirrored back in real time, to reflect one's own brain activity. Those who take part in the study will be randomly assigned to receive either tones that are based on their brain activity/brainwaves, or random tones.

Study II evaluates symptoms of mTBI through either 10 office sessions of the same acoustic stimulation linked to brain activity/brainwaves as Study I compared to 5 office sessions of acoustic stimulation plus intermittent very low level electrical stimulation of the scalp linked to brain activity.

Condition or disease	Intervention/treatment	Phase
Post-Concussion Symptoms; Insomnia; Pain, Chronic; Depressive Symptoms	Device: HIRREM-SOP or Cereset; Device: Cereset 2x	Not Applicable

Detailed Description:

Persistent symptoms after concussion or mild traumatic brain injury (mTBI), such as pain and sleep difficulties, may be related to altered patterns of brain electrical activity, including changes in amplitude and frequency. The purpose of these two studies is to evaluate a noninvasive, closed-loop, acoustic stimulation neurotechnology, High resolution, relational, resonance-based, electroencephalic mirroring, with standard operating procedures, HIRREM-SOP. This intervention is intended to improve symptoms by supporting self-optimization of brain electrical activity. Put more simply, musical tones will be played to echo, or mirror one's own brainwaves, in real time, allowing opportunity for auto-calibration, self-adjustment, and equilibration of that brain activity. The hypothesis is that over the course of ten 90-minute sessions, symptoms related to mTBI, will improve much more with musical tones linked to brainwaves than with random tones.

Participants will be enrolled at Uniformed Services University/Walter Reed National Military Medical Center in Bethesda, MD, and Womack Army Medical Center, Fort Bragg, NC.

The 106 participants in the first part of the study can be active duty or recently retired service members, or their family members, who have had a mTBI at least three months and not more than ten years ago, with related symptoms. Participants will be randomized to either musical tones that reflect their own brain activity, or random tones. A technologist will oversee each session in which the tones are presented. Participants and those analyzing outcomes will be blinded to the nature of the acoustic stimuli received. The primary outcome will be the change in Neurobehavioral Symptom Inventory scores at three months, and the final follow-up will occur be at six months. Changes in sleep, pain, dizziness, and general quality of life will also be measured.

Study II will recruit up to 100 participants with the goal of randomizing 86 participants to one of the two interventional arms equally across the same locations with the same inclusions criteria. This study seeks to establish a non-inferiority for the shorter course intervention. The primary outcome measure will continue to be the NSI score measured post-intervention and at 3-months. Changes in sleep, pain, dizziness, and general quality of life will also be measured.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized controlled trial
• Masking: None (Open Label)

Masking Description

Study I - Single-blind (participants and outcomes assessors blinded, but technologists are not), up to 126 enrolled (target of 106 being randomized)

Study II - Controlled (participants randomly assigned to one of two interventional arms, no blinding due to 5 or 10 sessions), up to 110 enrolled (target of 86 being randomized)

• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trials of Closed-loop Allostatic Neurotechnology to Improve Sensory Function and Pain Management After Traumatic Brain Injury
• Actual Study Start Date: August 28, 2018
• Estimated Primary Completion Date: July 1, 2023
• Estimated Study Completion Date: July 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: HIRREM-SOP or Cereset; HIRREM-SOP is a novel, noninvasive, closed-loop, BrainEcho, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. This group will have 10 sessions.	Device: HIRREM-SOP or Cereset; HIRREM-SOP for ten 90 minute sessions
Active Comparator: Cereset 2x; Participants randomized to the Cereset 2x group will be seated in a comfortable zero-gravity chair identical to those in the HIRREM-SOP arm. They will listen to a pattern of musical notes linked to their brain activity patterns, but also receive intermittent very low level electrical stimulation of the scalp linked to brain activity. This group will only have 5 sessions,	Device: Cereset 2x; Cereset 2x for five 90 minute sessions

Outcome Measures

Primary Outcome Measures :

1. Neurobehavioral Symptom Inventory (NSI) [ Time Frame: decrease in the score three months following enrollment ]
   0 = None - Rarely if ever present; not a problem at all and 4= Very Severe - Almost always present and I have been unable to perform at work, school or home due to this problem; I probably cannot function without help.

Secondary Outcome Measures :

1. PATIENT'S GLOBAL IMPRESSION OF CHANGE (PGIC) SCALE [ Time Frame: Score increases three months after enrollment ]
   • No change (or condition has gotten worse) (1); to
   • A great deal better and a considerable improvement that has made all the difference (7)
2. HIT-6 Headache Impact Test [ Time Frame: improve headache patterns by decreasing point score 3 months after enrollment ]
   based on scale from never (6 pts) to always (13 pts)
3. The Dizziness Handicap Inventory ( DHI ) [ Time Frame: Lower the point total for those whose base line is greater than 10 pts at evaluation 3 months following enrollment ]

   To each item, the following scores can be assigned:

   No=0 Sometimes=2 Yes=4

   Scores:

   Scores greater than 10 points should be referred to balance specialists for further evaluation.

   16-34 Points (mild handicap) 36-52 Points (moderate handicap) 54+ Points (severe handicap) Scores are assigned No=0 Sometimes=2 Yes=4; total greater than 10 requires further evaluation and 54+ severe handicap

4. PCL-5 The PTSD Checklist for DSM-5 [ Time Frame: Lower the score three months after enrollment ]
   Questions scored as 0=not at all; to, 4=Extremely
5. Patient Health Questionnaire-9 (PHQ-9) [ Time Frame: Lower the score three months after enrollment ]
   Frequency of being bothered by the conditions where 0=not at all; to 3=nearly every day

Other Outcome Measures:

1. Defense and Veterans Pain Rating Scale [ Time Frame: Score decrease three months after enrollment ]
   (0) No Pain; to (10) As bad as it could be nothing else matters.
2. Insomnia Severity Index [ Time Frame: Score decrease three months after enrollment ]
   0-7 = No clinically significant insomnia 8-14 = Subthreshold insomnia 15-21 = Clinical insomnia (moderate severity) 22-28 = Clinical insomnia (severe)
3. Automated Neuropsychological Assessment Metrics (ANAM) [ Time Frame: improve reaction times three months after enrollment ]
   used to measure simple reaction time and procedural reaction time

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 1 Must have symptoms related to concussion or TBI, not healthy controls Age 18 years or older.
• 2 Active duty or retired military service member, or dependent beneficiary.
• 3 History of mild TBI, confirmed by administration of the Ohio State University TBI
• Identification Method Interview.
• 4 At least three months, and no more than ten years, since their most recent TBI.
• 5 Persistent symptoms temporally related, or otherwise attributable to, the TBI, such as
• headache or chronic pain, sensory disturbance including auditory, visual or other sensory
• symptoms, balance difficulties, or dizziness. After obtaining informed consent, sufficient
• severity of symptoms for entry into the study will be confirmed by administration of the
• Neurobehavioral Symptom Inventory (NSI), with a score of 23 or higher required for
• inclusion.
• 6 Willingness to be randomly assigned to one of the two treatment groups and to provide
• data for all study measures.
• 7 Willingness to abstain from alcohol or recreational drug use throughout the intervention
• period and up to 3 weeks after completion of the final office-based intervention session.
• This abstention period is intended to support the stabilization of new brain activity
• patterns that may result from the intervention.
• 8 For individuals using any of the following medication classes (either regularly scheduled
• or PRN), a willingness both to discontinue or hold those medications at least five (5) halflives
• prior to the initiation of study procedures, and throughout the period of participation
• in the study, as well as to sign a release enabling contact between study staff and their
• prescribing provider, to ensure that the prescriber deems that holding said medication
• during the study period is permissible and reasonable: benzodiazepines, opioids, antipsychotics,
• mood-stabilizers, anti-convulsants, non-benzodiazepine sleep aids (including
• but not limited zolpidem, eszoplicone, zaleplon, trazadone, and diphenhydramine), other
• prescribed sedative-hypnotics, or medical marijuana or cannabinoid medication.
• 9 Willingness to abstain from initiation of PRN/as needed usage of the above listed
• medications throughout the period of study participation. This criterion only applies to
• new PRN prescription or usage. There is no requirement to abstain from a new, regularly scheduled prescription for one of the above medications during the course of the study, if the participant's provider
• deems such usage to be indicated. The potential impact of the initiation of any such
• medications during the study will be assessed by conducting sensitivity analyses after the
• completion of the study.
• 10 Willingness to alert study investigators of any changes in their medication usage
• throughout the course of their study participation.

Exclusion Criteria:

• 1 Unable or unwilling to demonstrate an understanding of the nature and intent of the
• study, and/or to complete informed consent procedures.
• 2 A history of moderate or severe TBI.
• 3 The diagnosis of a psychotic disorder (including schizophrenia and schizoaffective
• disorder), severe depression (PHQ-9 score > 20), bipolar disorder, or active suicidal or
• homicidal ideation.
• 4 Physically unable to come to the study visits, or to sit in a chair for up to two hours.
• 5 Inability to hear and repeat a phrase spoken at normal conversational volume.
• 6 Meeting criteria for a current alcohol or substance use disorder.

Contacts and Locations

Contacts

Contact: Lee Gerdes, M Div; 480-588-6840; lee.gerdes@brainstatetech.com

Contact: Charles H Tegeler, MD; 336-716-7651; ctegeler@wfubmc.edu

Locations

United States, Maryland

Uniformed Services University; Recruiting

Bethesda, Maryland, United States, 20814

Contact: Paula Bellini 301-295-5840 Paula.bellini.ctr@usuhs.edu

Principal Investigator: Michael J Roy, MD, MPH

United States, North Carolina

Womack Army Medical Center; Recruiting

Fort Bragg, North Carolina, United States, 28310

Contact: Wesley R. Cole, Ph. D. 910-907-7709 wesley.r.cole.civ@mail.mil

Contact: Nora Rachels 910-908-2280 Nora.rachels.ctr@mail.mil

Sponsors and Collaborators

Brain State Technologies, LLC

Uniformed Services University of the Health Sciences

Womack Army Medical Center

More Information

• Responsible Party: Brain State Technologies, LLC
• ClinicalTrials.gov Identifier: NCT03649958
• Other Study ID Numbers: MED-83-8754; W81XWH1720057 ( Other Grant/Funding Number: CDMRP )
• First Posted: August 28, 2018
• Last Update Posted: April 7, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Brain State Technologies, LLC:

concussion; mTBI; headache; insomnia; PTS; anxiety; pain; depression; sleep

Additional relevant MeSH terms:

Brain Injuries; Sleep Initiation and Maintenance Disorders; Brain Injuries, Traumatic; Post-Concussion Syndrome; Chronic Pain; Depression; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Mental Disorders; Behavioral Symptoms; Pain; Neurologic Manifestations; Brain Concussion; Head Injuries, Closed; Wounds, Nonpenetrating