Clinical trial NCT03230890: HIRREM in Military Personnel
Official title: HIRREM for Mitigation of PTSD Symptoms in Military Personnel
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stress Disorders, Post-Traumatic
Keywords: PTSD
military
neurotechnology
HIRREM
allostasis
heart rate variability
baroreflex sensitivity
closed loop
acoustic stimulation
neural oscillations
autonomic
hyperarousal
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Brain State Technologies, LLC
First posted: 2017-07-27
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single site, non-randomized, single arm, open label design,with collection of outcome measures before, and at intervals after the intervention
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effects associated with the use of in-office High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) for participants with symptoms of military-related traumatic stress. This is a single site, non-randomized, open label pilot study. Outcome measures collected before, and after the intervention evaluate effects on self-reported symptoms, autonomic cardiovascular regulation, functional measures, blood and saliva biomarkers of stress and inflammation, and network connectivity on whole brain, rest MRI testing. Self-reported symptom outcomes will also be collected remotely at 1, 3, and 6 months after completion of intervention. The study will assess feasibility in this cohort, focused on the Special Operations community, will provide estimates of effect size, and durability of symptom changes, while providing important pilot data for future proposals and investigations.

Detailed description: This will be an open label, single site, pilot, clinical research study. Up to 40 active duty military personnel, or recent Veterans, age 18 or older, who have been diagnosed with PTSD, have received treatment for, are referred by military medical personnel for, or have active symptoms of military-related traumatic stress, with or without mild TBI, will be recruited to receive up to 24 HIRREM sessions over 2 weeks. For those who self-refer, and do not have a prior diagnosis or treatment for PTSD, active symptoms will be identified by a screening PCL-M score of 50 or greater. Recruitment of 40 participants will allow us to achieve the goal of 36 participants to complete the intervention, allowing for the possibility of dropouts. The primary outcome will be differential change in the PCL-M from baseline to completion of HIRREM sessions. Secondary measures include the Insomnia Severity Index (ISI), the Center for Epidemiological Studies Depression Scale (CES-D), an anxiety measure (GAD-7), a quality of life measure (EQ-5D), an autonomic symptom measure (Compass 31), and a daily sleep diary, as well as physiological measures including heart rate (HR), and blood pressure (BP), with calculation of heart rate variability measures (HRV), and baroreflex sensitivity (BRS). Functional measures will include reaction time (drop-stick paradigm), and grip strength (hydraulic dynamometer), and analysis of brain patterns. If there is a history of TBI, a Rivermead Post-Concussion Symptoms Questionnaire (RPQ) will be added. There will be pre- and post-intervention data collection for all measures (baseline, V1, and at completion of HIRREM sessions, V2). Self-report measures will also be repeated by phone at 1, 3, and 6 months after completion of sessions (V3, V4, and V5 respectively). The online sleep diary will be maintained from V1 until V3. A brainwave assessment will be obtained at V1.

Eligibility criteria: Inclusion Criteria:

Active duty military personnel, or recent veterans (Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn), men and women, with a diagnosis of PTSD, or active symptoms suggesting PTSD as identified by a screening PCL-M score of 50 or greater, with or without traumatic brain injury (TBI), are eligible to participate in the study.

Exclusion Criteria:

* Unable, unwilling, or incompetent to provide informed consent
* Physically unable to come to the study visits, or to sit in a chair for several hours
* Known seizure disorder
* Severe hearing impairment (because the subject will be using ear buds during HIRREM)
* Ongoing need for treatment with opiate, benzodiazepine, or anti-psychotic medications, anti-depressant medications (SSRI, or SNRI's), sleep medications such as zolpidem or eszopiclone, stimulants such as Adderall, Provigil, or Ritalin, or thyroid hormone
* Anticipated and ongoing use of recreational drugs, alcohol, or energy drinks
* Lack of internet or smart phone access (will maintain remote access daily sleep diary through 1 month post-HIRREM visit)

Primary outcomes:
measure: Change in PCL-M Score From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the HIRREM intervention (up to 12 days later)
Secondary outcomes:
measure: Change in Center for Epidemiologic Studies Depression Scale (CES-D) Score From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Insomnia Severity Index (ISI) Score From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Generalized Anxiety Disorder-7 (GAD-7) Score From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Rivermead Post-Concussion Symptoms Questionnaire (RPQ) Score From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in EQ-5D Score From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Heart Rate Variability Measure of SDNN From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Baroreflex Sensitivity HF Alpha From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Baroreflex Sensitivity Sequence Up From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Baroreflex Sensitivity Sequence Down From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Baroreflex Sensitivity Sequence All From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Drop Stick Reaction Time From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Grip Strength From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Functional MRI From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Salivary Biomarker Cortisol for Stress From Baseline to 12 Days
timeFrame: Salivary biomarker for stress will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
measure: Change in Epigenetic Markers From Baseline to 12 Days
timeFrame: Blood for epigenetic markers will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
measure: Change in Sleep Latency Score From Baseline to 42 Days
timeFrame: Sleep diary data will be collected daily via online access from baseline to a month following completion of intervention (up to 42 days)
measure: Change in C-reactive Protein for Stress and Inflammation Score From Baseline to 12 Days
timeFrame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
measure: Salivary Biomarker for Stress From Baseline to 12 Days
timeFrame: Salivary biomarker Alpha-Amylase for stress will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Charles H Tegeler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tegeler CH, Cook JF, Tegeler CL, Hirsch JR, Shaltout HA, Simpson SL, Fidali BC, Gerdes L, Lee SW. Clinical, hemispheric, and autonomic changes associated with use of closed-loop, allostatic neurotechnology by a case series of individuals with self-reported symptoms of post-traumatic stress. BMC Psychiatry. 2017 Apr 19;17(1):141. doi: 10.1186/s12888-017-1299-x.
citation: Tegeler CH, Tegeler CL, Cook JF, Lee SW, Gerdes L, Shaltout HA, Miles CM, Simpson SL. A Preliminary Study of the Effectiveness of an Allostatic, Closed-Loop, Acoustic Stimulation Neurotechnology in the Treatment of Athletes with Persisting Post-concussion Symptoms. Sports Med Open. 2016 Dec;2(1):39. doi: 10.1186/s40798-016-0063-y. Epub 2016 Sep 14.
citation: Fortunato JE, Tegeler CL, Gerdes L, Lee SW, Pajewski NM, Franco ME, Cook JF, Shaltout HA, Tegeler CH. Use of an allostatic neurotechnology by adolescents with postural orthostatic tachycardia syndrome (POTS) is associated with improvements in heart rate variability and changes in temporal lobe electrical activity. Exp Brain Res. 2016 Mar;234(3):791-8. doi: 10.1007/s00221-015-4499-y. Epub 2015 Dec 8.
citation: Gerdes L, Tegeler CH, Lee SW. A groundwork for allostatic neuro-education. Front Psychol. 2015 Aug 17;6:1224. doi: 10.3389/fpsyg.2015.01224. eCollection 2015.
citation: Tegeler CH, Shaltout HA, Tegeler CL, Gerdes L, Lee SW. Rightward dominance in temporal high-frequency electrical asymmetry corresponds to higher resting heart rate and lower baroreflex sensitivity in a heterogeneous population. Brain Behav. 2015 Jun;5(6):e00343. doi: 10.1002/brb3.343. Epub 2015 May 1.
citation: Tegeler CH, Tegeler CL, Cook JF, Lee SW, Pajewski NM. Reduction in menopause-related symptoms associated with use of a noninvasive neurotechnology for autocalibration of neural oscillations. Menopause. 2015 Jun;22(6):650-5. doi: 10.1097/GME.0000000000000422.
citation: Lee SW, Gerdes L, Tegeler CL, Shaltout HA, Tegeler CH. A bihemispheric autonomic model for traumatic stress effects on health and behavior. Front Psychol. 2014 Aug 1;5:843. doi: 10.3389/fpsyg.2014.00843. eCollection 2014.
citation: Gerdes L, Gerdes P, Lee SW, H Tegeler C. HIRREM: a noninvasive, allostatic methodology for relaxation and auto-calibration of neural oscillations. Brain Behav. 2013 Mar;3(2):193-205. doi: 10.1002/brb3.116. Epub 2013 Jan 14.
citation: Tegeler CL, Gerdes L, Shaltout HA, Cook JF, Simpson SL, Lee SW, Tegeler CH. Successful use of closed-loop allostatic neurotechnology for post-traumatic stress symptoms in military personnel: self-reported and autonomic improvements. Mil Med Res. 2017 Dec 22;4(1):38. doi: 10.1186/s40779-017-0147-0.