Stress Disorders, Post-TraumaticNCT03230890
HIRREM in Military Personnel
A study testing HIRREM in people with Stress Disorders, Post-Traumatic, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stress Disorders, Post-Traumatic
- What is being tested?
- HIRREM
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Feb 2015to 5 Apr 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
About this study
Official title: HIRREM for Mitigation of PTSD Symptoms in Military Personnel
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.
Read the 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.
- Conditions
- Stress Disorders, Post-Traumatic
- Being tested
- HIRREM
- Keywords
- PTSD, military, neurotechnology, HIRREM, allostasis, heart rate variability, baroreflex sensitivity, closed loop, acoustic stimulation, neural oscillations, autonomic, hyperarousal
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIRREMDevice
HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.
| Study group | Role | What they receive |
|---|---|---|
| HIRREM | Experimental | This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). Receives: Device: HIRREM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PCL-M Score From Baseline to 12 Days
The PTSD Checklist (PCL) - Military (M) is a symptom checklist to measure stress severity due to a traumatic experience in military settings. The PCL-M measures the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (DSM-IV) of PTSD symptoms based on traumatic life experience. Seventeen items are rated on a Likert scale from 1 (not at all) to 5 (extremely), with a total score ranging from 17 to 85. Higher scores suggest more PTSD symptoms. Primary outcome for this pilot study will be change in PCL-M score from baseline to the immediate post-intervention in-person data collection at the completion of the HIRREM intervention (up to 12 days later).
Measured: Data is collected at baseline and immediately following completion of the HIRREM intervention (up to 12 days later)
Secondary outcomes (19)
Change in Center for Epidemiologic Studies Depression Scale (CES-D) Score From Baseline to 12 Days
The CES-D is a 20-item survey assessing affective depressive symptomatology to screen for risk of depression. Scores range from 0-60, with a score of 16 commonly used as a clinically relevant cut-off. Higher scores suggest more depressive symptomatology. Secondary outcome with the CES-D will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Insomnia Severity Index (ISI) Score From Baseline to 12 Days
The severity of insomnia symptoms is measured using the ISI with each data collection visit. The ISI is a 7 question measure, with responses from 0-4 for each question, yielding scores ranging from 0-28. Higher scores indicate the strength of the insomnia severity. Secondary outcome with the ISI will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Generalized Anxiety Disorder-7 (GAD-7) Score From Baseline to 12 Days
The Generalized Anxiety Disorder-7 (GAD-7) is a seven item screening tool for anxiety that is widely used in primary care. Each item is rated from 0 (not at all) to 3 (nearly every day). Scores range from 0 to 21 with higher scores suggesting more anxiety. Secondary outcome with the GAD-7 will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Rivermead Post-Concussion Symptoms Questionnaire (RPQ) Score From Baseline to 12 Days
The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is a 16-item survey that assesses the severity of the most common post-concussion symptoms on a scale of 0 to 4, with a total score range from 0 to 64 (least to greatest symptom severity). Items are compared to levels before the head injury and are reported as a 24 hour recall. Secondary outcome with the RPQ will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in EQ-5D Score From Baseline to 12 Days
The EQ-5D is a brief, standardized measure of health status developed by the EuroQol Group, and is a paper and pencil survey providing a single index value for health status. Secondary outcome with the EQ-5D will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Global health rating question is reported (0-100, with 100 being in the best health possible).
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Heart Rate Variability Measure of SDNN From Baseline to 12 Days
Secondary autonomic outcome with heart rate variability will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Heart rate variability is measured in the time domain as standard deviation beat-to-beat interval (SDNN, milliseconds). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed. Higher SDNN values suggest better autonomic regulation.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Baroreflex Sensitivity HF Alpha From Baseline to 12 Days
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard Baroreflex Sensitivity (BRS) software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the frequency domain as high frequency (HF) alpha index (ms2). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in HF alpha suggest better autonomic regulation.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Baroreflex Sensitivity Sequence Up From Baseline to 12 Days
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard Baroreflex Sensitivity (BRS) software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence Up (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence Up suggest better autonomic regulation.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Baroreflex Sensitivity Sequence Down From Baseline to 12 Days
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard Baroreflex Sensitivity (BRS) software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence Down (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence Down suggest better autonomic regulation.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Baroreflex Sensitivity Sequence All From Baseline to 12 Days
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard Baroreflex Sensitivity (BRS) software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence All (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence All suggest better autonomic regulation.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Drop Stick Reaction Time From Baseline to 12 Days
Reaction testing is measured by a drop-stick apparatus that has been validated as a way to quantify the impact of athletic concussion on psychomotor performance. Following two practice trials, participants perform eight trials, and a mean distance value is calculated. Secondary functional outcome with drop-stick reaction time will be analyzed for changes in distance from baseline to the in person data collection immediately after completion of the intervention. A lower average indicates a faster reaction time.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Grip Strength From Baseline to 12 Days
Grip strength will evaluated using a hydraulic hand dynamometer (Baseline Hydraulic Hand Dynamometer, ranges from 0 to 300 lbs). Both right and left hand will be evaluated, and the greatest force generated during three trials will be used for analysis. A higher score indicates stronger grip strength.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Functional MRI From Baseline to 12 Days
Anatomical and physiological brain imaging will be performed during a 1-hour imaging session at baseline and immediately following completion of the intervention. This will include imaging sequences such as high resolution structural scans. Brain network data will be collected using blood oxygenation level dependent (BOLD) scans. These scans will be collected under various states such as at rest. All images will be acquired using a 3 Tesla Siemens MRI scanner. Whole-brain network connectivity will be assessed using blood oxygenation level dependent (BOLD) imaging. Unit of measure is percentage of BOLD signal change. Community structure will be determined for each participant pre- and post-intervention. This project will focus on the community including the Default Mode Network (DMN). Participant strength of the community structure will be determined of the DMN. Permutation analysis will be used to evaluate significant pattern change in specific networks.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days
Blood for a panel of biomarkers for stress will be collected at enrollment, and after completion of the intervention. The panel includes Ang II, Ang 1-7, Epinephrine, Norepinephrine, C-reactive protein, Vasopressin, IL-1, IL-6, and IL-10.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Salivary Biomarker Cortisol for Stress From Baseline to 12 Days
Saliva for salivary biomarker Cortisol, for stress, will be collected at enrollment, and after completion of the intervention.
Measured: Salivary biomarker for stress will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
Change in Epigenetic Markers From Baseline to 12 Days
DNA will be isolated from whole blood, collected in yellow-top Vacutainer tubes (ACD as the preservative), using the AutoPure LS system in the Genomics Center Core lab. DNA will be bisulfite-converted using the EZ DNA Methylation Gold kit (Zymo, Irvine, CA). To quantify DNA methylation at each site, investigators will use the HumanMethylationEPIC450 BeadChip (Illumina, Inc.). The methylation proportion for each site (beta value) is based on the ratio of the fluorescence intensity of the methylated versus the combined methylated \& unmethylated probes, \& will be determined with GenomeStudio (Illumina, Inc.). Ratio of 0 equals no methylation \& ratio of 1 equals total (100%) methylation." Effects of DNA methylation for a specific site are dependent on function of the regulated gene(s). For some genes, increased level methylation from the intervention may be beneficial, while for others an increased level may be detrimental. There is no universal way to interpret change in DNA methylation.
Measured: Blood for epigenetic markers will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
Change in Sleep Latency Score From Baseline to 42 Days
An online daily sleep diary to calculate sleep latency will be maintained from baseline, through the one month post-intervention remote data collection (roughly 42 days). Sleep latency is reported in minutes and a smaller score suggests falling asleep faster.
Measured: Sleep diary data will be collected daily via online access from baseline to a month following completion of intervention (up to 42 days)
Change in C-reactive Protein for Stress and Inflammation Score From Baseline to 12 Days
Blood for biomarker C-reactive protein for stress will be collected at enrollment, and after completion of the intervention.
Measured: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Salivary Biomarker for Stress From Baseline to 12 Days
Saliva for salivary biomarker Alpha-Amylase, for stress, will be collected at enrollment, and after completion of the intervention.
Measured: Salivary biomarker Alpha-Amylase for stress will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2017
- Study start16 Feb 2015
- Primary completionApr 2021
- Study completion5 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Stress Disorders, Post-TraumaticStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single site, non-randomized, single arm, open label design,with collection of outcome measures before, and at intervals after the intervention
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Brain State Technologies, LLC
- Responsible party
- Sponsor
- Investigators
- Charles H Tegeler, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03230890
- Sponsor's protocol ID
- IRB00028990
- Status last verified
- Oct 2022
- First submitted
- 24 Jul 2017
- Last updated
- 14 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 28420362Tegeler 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.
PubMed 27747793Fortunato 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.
PubMed 26645307Gerdes 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.
PubMed 26347688Tegeler 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.
PubMed 26085968Tegeler 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.
PubMed 25668305Lee 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.
PubMed 25136325Gerdes 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.
PubMed 23532171Tegeler 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.
PubMed 29502530
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HIRREM for Mitigation of PTSD Symptoms in Military Personnel
- ClinicalTrials.gov ID
- NCT03230890
- Acronym / sponsor ID
- IRB00028990
- Conditions
- Stress Disorders, Post-Traumatic
- Keywords
- PTSD, military, neurotechnology, HIRREM, allostasis, heart rate variability, baroreflex sensitivity, closed loop
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Brain State Technologies, LLC
- Study start
- 16 Feb 2015 (actual)
- Primary completion
- Apr 2021 (actual)
- Study completion
- 5 Apr 2021 (actual)
- First posted
- 27 Jul 2017 (actual)
- Results
- Posted 14 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single site, non-randomized, single arm, open label design,with collection of outcome measures before, and at intervals after the intervention
| Arm | Type | Receives |
|---|---|---|
| HIRREM | Experimental | Device: HIRREMThis is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HIRREMHIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair. | Device | HIRREM |
Primary outcome
Change in PCL-M Score From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the HIRREM intervention (up to 12 days later)
The PTSD Checklist (PCL) - Military (M) is a symptom checklist to measure stress severity due to a traumatic experience in military settings. The PCL-M measures the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (DSM-IV) of PTSD symptoms based on traumatic life experience. Seventeen items are rated on a Likert scale from 1 (not at all) to 5 (extremely), with a total score ranging from 17 to 85. Higher scores suggest more PTSD symptoms. Primary outcome for this pilot study will be change in PCL-M score from baseline to the immediate post-intervention in-person data collection at the completion of the HIRREM intervention (up to 12 days later).
19 secondary outcomes
Change in Center for Epidemiologic Studies Depression Scale (CES-D) Score From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Insomnia Severity Index (ISI) Score From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Generalized Anxiety Disorder-7 (GAD-7) Score From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Rivermead Post-Concussion Symptoms Questionnaire (RPQ) Score From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in EQ-5D Score From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Heart Rate Variability Measure of SDNN From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Baroreflex Sensitivity HF Alpha From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Baroreflex Sensitivity Sequence Up From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Baroreflex Sensitivity Sequence Down From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Baroreflex Sensitivity Sequence All From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Drop Stick Reaction Time From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Grip Strength From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Functional MRI From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Salivary Biomarker Cortisol for Stress From Baseline to 12 Days
Time frame: Salivary biomarker for stress will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
Change in Epigenetic Markers From Baseline to 12 Days
Time frame: Blood for epigenetic markers will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
Change in Sleep Latency Score From Baseline to 42 Days
Time frame: Sleep diary data will be collected daily via online access from baseline to a month following completion of intervention (up to 42 days)
Change in C-reactive Protein for Stress and Inflammation Score From Baseline to 12 Days
Time frame: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)
Salivary Biomarker for Stress From Baseline to 12 Days
Time frame: Salivary biomarker Alpha-Amylase for stress will be obtained at baseline and immediately following completion of the intervention (up to 12 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28420362Tegeler 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.
- Background: PubMed 27747793Tegeler 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.
- Background: PubMed 26645307Fortunato 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.
- Background: PubMed 26347688Gerdes 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.
- Background: PubMed 26085968Tegeler 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.
- Background: PubMed 25668305Tegeler 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.
- Background: PubMed 25136325Lee 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.
- Background: PubMed 23532171Gerdes 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.
- Derived from this study: PubMed 29502530Tegeler 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles H Tegeler, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HIRREM in people with Stress Disorders, Post-Traumatic, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in PCL-M Score From Baseline to 12 Days (time frame: Data is collected at baseline and immediately following completion of the HIRREM intervention (up to 12 days later)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03230890, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2023.