Study of the Effects of HIRREM-SOP for Insomnia

• ClinicalTrials.gov Identifier: NCT03607994
• Recruitment Status: Active, not recruiting
• First Posted: July 31, 2018
• Results First Posted: June 22, 2021
• Last Update Posted: October 27, 2021
• Sponsor: Wake Forest University Health Sciences
• Information provided by (Responsible Party): Wake Forest University Health Sciences

Study Description

Brief Summary:

Prior research studies have shown benefit for use of a technique called High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®), to reduce symptoms of moderate to severe insomnia. HIRREM uses scalp sensors to monitor brain electrical activity, and software algorithms translate selected brain frequencies into audible tones in real time. Those tones (acoustic stimulation) are reflected back to participants via ear buds in as little as four milliseconds, providing the brain an opportunity to self-adjust and balance its electrical pattern.

The purpose of this research study is to determine the effects of HIRREM-SOP, an updated version of this technology that is based on the HIRREM approach, but now includes new hardware and software, a standardized series of HIRREM protocols, and a fixed number of sessions. Adults over the age of 18 who have documented sleep trouble that place them in the category of subthreshold (mild), moderate, or severe clinical insomnia as defined by the Insomnia Severity Index, are eligible to participate in the study.

Condition or disease	Intervention/treatment	Phase
Insomnia; Sleep Deprivation	Device: HIRREM-SOP; Device: NCC	Not Applicable

Detailed Description:

High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®) is a closed-loop, allostatic, acoustic stimulation neurotechnology that uses software-guided algorithmic analysis to identify and translate selected brain frequencies into audible tones to support real-time self-optimization of brain activity. Prior research demonstrates that the use of HIRREM is associated with reduced symptoms of insomnia, and traumatic stress and anxiety, and improved autonomic cardiovascular regulation across heterogeneous cohorts. HIRREM has been safe and well tolerated in about 500 people across six IRB-approved studies. However, the current in-office HIRREM approach remains very operator dependent (extensive Technologist education and experience) and takes a sizeable time commitment from the participant (typically ten or more sessions of 90-120 minutes each). To reduce participant time required, and operator dependence, while increasing scalability, a new generation of hardware and software has been developed. While based on the same core technology and algorithms to mirror brainwaves with audible tones, this includes the use of faster, 64-bit processing architecture for faster feedback, the use of 4 sensors, and the use of standard protocols, all done with eyes closed (HIRREM-SOP). Although only 2 sensors are active at a time, applying 4 sensors, for which the software can switch from one pair to the other automatically, cuts in half the number of sensor placement changes needed, with reduced session time and interruptions. A modified placebo condition now includes random timing and pitch of the tones, which have not been acoustically engineered. This pilot study will evaluate feasibility of this standardized, enhanced approach, and the effectiveness of blinding for the placebo condition in participants with symptoms of insomnia.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This study will compare acoustic stimulation linked to brainwave activity (HIRREM-SOP, along with continued current care, BCC) with acoustic stimulation not linked to brainwave activity (NCC, along with continued current care). The participants in the NCC group with will offered the opportunity to crossover and receive a course of BCC at the end of their original participation.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Randomized Controlled Pilot Trial of HIRREM-SOP for Insomnia
• Actual Study Start Date: November 19, 2018
• Actual Primary Completion Date: March 5, 2020
• Estimated Study Completion Date: March 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: HIRREM-SOP (BCC; Acoustic stimulation linked to brainwave activity and continued current care.	Device: HIRREM-SOP; HIRREM-SOP is an updated version of HIRREM. It is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time.
nonspecific acoustic stimulation (NCC); Continued current care and acoustic stimulation that is not linked to brainwave activity.	Device: HIRREM-SOP; HIRREM-SOP is an updated version of HIRREM. It is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time.; Device: NCC; Nonspecific acoustic stimulation with randomly generated tones not linked to brain activity.

Outcome Measures

Primary Outcome Measures :

1. Change in ISI Score From V1 to V3 [ Time Frame: Baseline, V2 (0-14 days after intervention completion), V3 (4-6 weeks following V2) ]
   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 Measures :

1. Number of Participants That Believe They Are Receiving HIRREM-SOP [ Time Frame: Baseline, before Session 5, V2 (0-14 days after intervention completion), V3 (4-6 weeks following V2) ]
   The participant will indicate which arm of the intervention they believe they are receiving. The effectiveness will be evaluated based on the expectation measure regarding group assignment prior to the 5th session.

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:

• Clinical Insomnia (Insomnia Severity Index ≥ 8) persisting by self-report for at least a month
• Subjects must have the ability to comply with basic instructions and be able to comfortably sit still with the sensor leads attached

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
• Known obstructive sleep apnea
• Diagnosed periodic limb movement disorder or known restless legs syndrome
• Known urinary problem (i.e. benign prostatic hypertrophy) which is the likely cause of the sleep disturbance
• Severe hearing impairment (because the subject will be using ear buds during HIRREM-SOP)
• 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
• Weight is over the chair limit (285 pounds)
• Currently in another active intervention research study
• Previous history of receiving or using HIRREM, BWO, HIRREM-SOP, or the wearable B2

Contacts and Locations

Locations

United States, North Carolina

Department of Neurology, Wake Forest School of Medicine

Winston-Salem, North Carolina, United States, 27104

Sponsors and Collaborators

Wake Forest University Health Sciences

Investigators

• Principal Investigator: Charles H Tegeler, MD; Wake Forest University Health Sciences

  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences:

Study Protocol and Statistical Analysis Plan  [PDF] September 12, 2019

Informed Consent Form  [PDF] June 11, 2019

More Information

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT03607994
• Other Study ID Numbers: IRB00051980
• First Posted: July 31, 2018
• Results First Posted: June 22, 2021
• Last Update Posted: October 27, 2021
• Last Verified: June 2021

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 Wake Forest University Health Sciences:

Neurotechnology; Autonomic Dysregulation; Hyperarousal; Brain Electrical Activity; Closed-loop; Acoustic Stimulation; Allostasis; Insomnia; HIRREM-SOP; Sleep Deprivation

Additional relevant MeSH terms:

Sleep Initiation and Maintenance Disorders; Sleep Deprivation; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Neurologic Manifestations