Cereset Research For Chronic Nausea

Randomized Controlled Pilot Trial of Cereset Research For Chronic Nausea

This study will explore the use of Cereset Research for symptoms associated with refractory chronic nausea in patients with gastroparesis (GP) in a randomized, clinical trial.

Study Overview

• Status: Withdrawn
• Conditions: Quality of Life; Nausea; Vomiting; Stress; Anxiety; Gastroparesis; Heart Rate Variability; Hyperarousal
• Intervention / Treatment: Device: Cereset Research

Detailed Description

Cereset Research (CR) is a noninvasive, close-loop, acoustic stimulation brain feedback system. CR translates brainwaves in real time, echoing them immediately via earbuds. This supports the brain to auto calibrate, self adjust, and relax (acoustic neuromodulation). The brain wave patterns are observed to shift towards improved balance and reduced hyperarousal, getting unstuck from what have become stuck patterns related to trauma and stress. Previous clinical trials using CR, as well as the legacy technology HIRREM, have shown significant benefit to reduce symptoms (stress, anxiety, depression, insomnia, Post-traumatic stress disorder (PTSD), persistent post-concussion symptoms, hot flashes, and others). Improved autonomic nervous system function has also been documented) heart rate variability and variable reflex sensitivity), as well as improved network connectivity on functional Magnetic resonance imaging (MRI) before and after the intervention.

Gastroparesis with normal gastric emptying, and associated chronic nausea, is a challenging clinical condition. There is associated autonomic dysfunction, along with many behavioral symptoms, and effective treatments are lacking. Based on prior studies, there is a reason to believe that CR may have beneficial effects for such patients. This controlled clinical trial will enroll up to 24 adults, age 18 or older, who have symptoms of chronic nausea (due to gastroparesis and who are not taking medications or supplements for management of symptoms) with a goal of 20 to complete the intervention. Participants will be randomly assigned to either an Early Intervention (EI) group which will receive 6 CR sessions over 4 weeks of audible tones echoing current brainwave activity, following enrollment, or a Delayed Intervention (DI) group which will continue current care only and will serve as a control group. Participants in both groups will continue their other current care throughout the study.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects with chronic drug- refractory, nausea and vomiting (ages 18 and up)
• Solid-phase gastric emptying studies show either normal gastric emptying or delayed gastric emptying
• Referring physician will confirm eligibility based on Rome-IV criteria
• Normal upper endoscopy or upper GI series and normal gallbladder tests
• Stable gastrointestinal symptoms with total GCSI score of greater than or equal to 21
• Ability to sign informed consent
• Ability to comply with basic instructions and be able to sit still, comfortably during sessions
• Willingness to complete the EGG and WLST

Exclusion Criteria:

• Non-gastrointestinal disorders which could explain symptoms in the opinion of the investigator
• Active H pylori infection
• Significant hepatic injury (elevated ALT, AST, bilirubin)
• Metabolic, mechanical, or mucosal inflammatory causes to explain GI symptoms such as inflammatory bowel disease, celiac disease, liver or pancreatic disease, or bowel obstruction
• Patients with significant cardiac or cardiovascular disease, malignancy, or other comorbid conditions
• Use of narcotics more than three days per week or other drugs that affect motility (that cannot be held)
• Previous diagnosis or history of neurocardiogenic syncope, orthostatic hypotension, etc.
• Patients with pace makers
• Use of beta blockers which can interfere with heart rate variability recording
• Unable, unwilling, or incompetent to provide informed consent/assent
• Physically unable to come to the study visits, or to sit still, comfortably in a chair for up to 1.5 hours
• Severe hearing impairment (because the subject will be using ear buds during CR)
• Anticipated and ongoing use of alcohol or recreational drugs
• Weight is over the chair limit (400 pounds)
• Currently enrolled in another active intervention research study
• Prior use of: HIRREM, HIRREM-SOP, Brainwave Optimization (BWO), Cereset, Cereset Home, or a wearable configuration of the same (B2, or B2v2)
• Prior use of the following modalities within one month before enrollment: electroconvulsive therapy (ECT), prior use of transcranial magnetic stimulation (TMS), transcranial direct current stimulation (TDCS), alpha stimulation, eye movement desensitization and reprocessing (EMDR), brain spotting, neurofeedback, biofeedback, or deep brain stimulation (DBS)
• Known seizure disorder or unspecified seizure within the past 12 months
• Thoughts of suicide within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cereset Research; Intervention arm using 6 CR sessions	Device: Cereset Research; Device: Cereset Research The upgraded platform for medical research using the HIRREM technology has been rebranded as Cereset Research® (CR). This system uses the same core technology and algorithms to echo brainwaves in real-time using audible tones, as with HIRREM. The CR system also includes 64-bit processing architecture for faster feedback, the use of 4 sensors, and the use of standard protocols (with flexibility regarding the length and sequencing of the standard protocols), all done with eyes closed. Four sensors are applied to the scalp at a time. However, only two sensors are actively echoing feedback. The software automatically switches from one sensor pair to the other when needed. This reduces the number of sensor placement changes needed, resulting in shorter session time and fewer interruptions.
No Intervention: Continued Current Care; Participants will continue their current care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gastroparesis Cardinal Symptom Index (GCSI) scores	The Gastroparesis Cardinal Symptom Index (GCSI) is a 9-item scale within the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM).episodes). The severity of symptom response scale ranges from 0 ("none"), 1 ("mild"), 2 ("moderate"), 3 ("severe") to 4 ("very severe"). Score can range from 0 to 4. High scores reflect greater symptom severity.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGY-SYM) scores	The Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) is 20 items. This inventory includes six subscales of related GI distress including heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Individual item scores range from 0 (none) to 5 (very severe). The higher the score, the more severe the GI symptoms.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Nausea Profile (NP) scores	The Nausea Profile evaluates the experience of 3 dimensions which are involved in the complex feeling of nausea; somatic distress, Gastrointestinal (GI) distress, and emotional distress. The degree to which the patient felt/feels each of the following descriptors during the nauseous period is rated by the patient on a scale of 0 (not at all) to 9 (severely). Higher scores suggest more nausea.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Center for Epidemiologic Studies Depression Scale (CES-D) scores	The Center for Epidemiologic Studies Depression Scale (CES-D) is a depression scale, which will help to assess this co-morbidity. 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. The higher the score, the more suggestive of depressive symptoms.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Generalized Anxiety Disorder-7 (GAD-7) scores	The Generalized Anxiety Disorder-7 (GAD-7) is a seven-item screening tool for anxiety that is widely used in primary care. GAD-7 is a brief, reliable and valid measure of assessing generalized anxiety disorder. A score of 10 or greater on the GAD-7 represents a reasonable cut point for identifying cases. Cut points of 5, 10, and 15 might be interpreted as representing mild, moderate, and severe levels of anxiety.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Severity of Insomnia (ISI) scores	The ISI is a 7 question, self-reported measure to evaluate symptoms of insomnia, with responses from 0-4 for each question, yielding scores ranging from 0-28. Lower scores represent better outcomes.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Post-traumatic stress disorder (PTSD) Checklist for civilians (PCL-C) scores	The PTSD Checklist for civilians (PCL-C), measures the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (DSM-IV) Criteria B, C, & D of PTSD symptoms based on traumatic life experience either in civilian life. Seventeen items are rated on a Likert scale with a composite score range of 17 to 85. A score of 44 or higher correlates with probability of civilian-related PTSD. Higher scores suggest more traumatic stress.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Perceived Stress Scale (PSS) scores	The Perceived Stress Scale (PSS) is a ten-item psychological instrument for measuring the perception of stress. It is a measure of the degree to which situations in one's life are appraised as stressful. Items were designed to tap how unpredictable, uncontrollable, and overloaded respondents find their lives. The scale, with answers rated from 0-4, also includes a number of direct queries about current levels of experienced stress. Total scores range from 0-40. A lower score denotes a lower level of perceived stress.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Fatigue Severity Scale (FSS) scores	Fatigue Severity Scale (FSS) is a nine-item instrument to assess how fatigue interferes with daily activities. Items are scored on a 7-point scale ranging from 1=strongly disagree to 7=strongly agree. Total scores range from 9 to 63 and the higher the rating demonstrates greater fatigue severity.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life (PAGI-QOl) scores	Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) is a specific scale for how Gastrointestinal (GI) symptoms impact quality of life in those with GI disorders. The scale consists of 30-items scored from 0 (none of the time) to 5 (all of the time) with a recall period of the last 2-weeks. Lower scores suggest better outcomes.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Changes in European Quality of Life Five Dimension (EQ-5D) scores	The self-rating health question from the EQ-5D on a scale of 0-100 (0 = worst imaginable health state, 100 = best imaginable health state) will be administered to get a snapshot of overall health at that point in time.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in The Interpersonal Support Evaluation List (ISEL-12) scores	The Interpersonal Support Evaluation List - Shortened Version (ISEL-12) is a 12-item scale that was modified from a 40-item scale used to assess perceptions of social support. Three dimensions are evaluated: appraisal support, belonging support, and tangible support. Each item is scaled from 1 to 4 for "Definitely True" to "Definitely False." Total scores range from 0-36 and higher scores suggest more social support.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Short Form McGill Pain Questionnaire (MPQ) scores	Short Form McGill Pain Questionnaire (MPQ) will be given to those who also report chronic pain. The MPQ is made up of 78 words and scores range from 0 (no pain) to 78 (severe pain).	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Pain Interference questionnaire scores	The PROMIS Short Form Pain Interference questionnaire will be given too those who report chronic pain. The PROMIS short form is a 6-point Likert-type scale, with scores ranging from 1 (had no pain) to 6 (always) over a 7-day recall period. Higher scores suggest more pain interference	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Heart Rate Variability (HRV)	Measures of heart rate variability in frequency domain will be derived and measures integrated over specified frequency ranges.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Heart Rate (HR)	Continuous heart rate will be recorded while participant is breathing normally in seated position for 10 minutes using Faros 180 heart rate monitor (Bittium Corporation, Oulu, Finland). Beat to beat intervals (RRI) files will be generated at 1000 Hz via the data acquisition software. Files will be analyzed with Nevrokard HRV software (by Nevrokard Kiauta, d.o.o., Izola, Slovenia). Recordings will be visually inspected to ensure data quality (dropped beats or gross motion artifacts are excluded) and first 5 minutes of usable tracings will be analyzed.	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Change in Baroreflex Sensitivity (BRS)	BRS calculated by this method is based on quantification of sequences of at least three beats (n) in which SBP consecutively increases (UP sequence) or decreases (DOWN sequence), which are accompanied by changes in the same direction of the RRI of subsequent beats (n+1). The software scans the RRI and SBP records, identifies sequences, and calculates linear correlation between RRI and SBP for each sequence. The mean of all individual regression coefficients (slopes), a measure of sequence BRS, is calculated for Sequence UP, DOWN and ALL (ms/mmHg). 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 BRS software (Nevrokard BRS, Medistar, Ljubljana, Slovenia).	Baseline to V3 (8-10 weeks following completion of the intervention for EI; Baseline to V5 (8-10 weeks following completion of the intervention for DI)
Changes in Healthcare Utilization Survey	Clinic visit counts will be collected (ED, Urgent Care visits).	V3 (8-10 weeks following completion of the intervention for EI; V5 (8-10 weeks following completion of the intervention for DI)

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: Susanne Marcus Collins Foundation; Gastroenterology Project
• Investigators: Principal Investigator: Charles Tegeler, MD, Wake Forest University Health Sciences

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Actual): March 7, 2024
• Study Completion (Actual): March 7, 2024

Study Registration Dates

• First Submitted: December 28, 2021
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: quality of life; nausea; insomnia; anxiety; stress; gastroparesis; Electrogastrography; HIRREM; acoustic stimulation; neurotechnology; autonomic dysregulation; hyperarousal; brain electrical activity; Cereset research; water load satiety testing
• Additional Relevant MeSH Terms: Digestive System Diseases; Neurologic Manifestations; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Nausea; Vomiting; Gastroparesis
• Other Study ID Numbers: IRB00078418

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes