Cereset Research For Chronic Nausea

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Randomized Controlled Pilot Trial of Cereset Research For Chronic Nausea

Conditions
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Nausea, Gastroparesis, Stress, Anxiety, Hyperarousal, Quality of Life, Vomiting, Heart Rate Variability

Intervention / Treatment
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* Device: Cereset Research


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a single site, open label, randomized, wait-list controlled, pilot clinical trial. This study 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cereset Research<br>Intervention arm using 6 CR sessions | Device: Cereset Research<br>* 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.<br>|
| No Intervention: Continued Current Care<br>Participants will continue their current care. | |

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea, gastroparesis, stress, anxiety, insomnia, quality of life, neurotechnology, autonomic dysregulation, hyperarousal, brain electrical activity, acoustic stimulation, HIRREM, Cereset research, water load satiety testing, Electrogastrography