Abdominal Pain, Autonomic Nervous System Imbalance, Irritable Bowel Syndrome
Conditions
Brief summary
This is a prospective, double-blind, randomized, sham-controlled pilot study evaluating the efficacy of percutaneous electrical nerve field stimulation for the treatment of adult patients with irritable bowel syndrome (IBS).
Detailed description
IBS has a worldwide prevalence around 11% and is characterized by chronic or recurrent abdominal pain associated with altered bowel habits. Abnormalities within the brain-gut axis, visceral hypersensitivity, and dysfunction of the autonomic nervous system are important components contributing to the pathophysiology of IBS. Despite recent advances in medical therapies for IBS, a significant subgroup of patients fails to experience satisfactory relief of abdominal pain. Given evidence of anti-inflammatory and anti-nociceptive components of vagal nerve pathways, peripheral field stimulation of the vagus nerve may help reduce abdominal pain in patients with IBS. Percutaneous electrical nerve field stimulation (PENFS) administered via the IB-Stim device (Innovative Health Solutions, Versailles, IN, USA) has been shown to be efficacious in adolescent patients with abdominal-pain-related functional GI disorders, including IBS. This device uses discontinuous frequencies of stimulation to target central pain pathways through branches of cranial nerves V, VII, IX, and X that innervate the external ear and project to certain brainstem nuclei, including the nucleus tractus solitarius (NTS). The NTS then acts as a relay station to other brain areas involved in pain modulation and autonomic control, including the rostral ventral medulla, locus coeruleus, hypothalamus, and amygdala. In adolescent studies, PENFS was associated with a greater reduction in worst abdominal pain and composite abdominal pain scores from baseline as well as compared with a sham device after three weeks of treatment. These effects were sustained over an extended follow-up period with minimal to no side effects. In addition, a greater proportion of adolescents in the PENFS arm achieved at least a 30% reduction in worst abdominal pain scores from baseline after 3 weeks of treatment. The IB-Stim is the first device to be approved by the Food and Drug Administration (FDA) for the treatment of functional abdominal pain in adolescents aged 11-18 with IBS. However, the efficacy of PENFS in adults with IBS is not currently known. This study is a double-blind, randomized, sham-controlled pilot study evaluating the efficacy of PENFS using IB-Stim for the treatment of IBS symptoms in adult patients with IBS.
Interventions
DEVICEPeripheral Electrical Nerve Field Stimulation (PENFS) Device
Patients will complete daily worst abdominal pain and bowel habit questionnaires for 1 week prior to initial PENFS device placement to provide a baseline. At visit 1, patients will complete the Bowel Symptom Questionnaire, IBS Symptom Severity Scale (IBS-SSS), PROMIS Belly Pain Scale, Gas and Bloating, Constipation, and Diarrhea Scales, Hospital Anxiety and Depression Scale, and Visceral Sensitivity Index, heart rate variability will be measured, and they will have the initial PENFS device placed. Patients will complete daily worst abdominal pain (scale 0-10) questionnaires throughout the duration of the study. They will return every 7 days for a total of 4 visits for device replacement and additional questionnaires, including the IBS-SSS. Four devices will be placed in total (start of weeks 1, 2, 3, and 4). Stimulation time is 5 days/week during each of the 4 consecutive weeks. Additional questionnaires will be completed at the end of week 4 and at extended follow-up (8 weeks).
DEVICESham Device
Patients will complete daily worst abdominal pain and bowel habit questionnaires for 1 week prior to initial sham device placement to provide a baseline. At visit 1, patients will complete the Bowel Symptom Questionnaire, IBS Symptom Severity Scale (IBS-SSS), PROMIS Belly Pain Scale, Gas and Bloating, Constipation, and Diarrhea Scales, Hospital Anxiety and Depression Scale, and Visceral Sensitivity Index, heart rate variability will be measured, and they will have the initial sham device placed. Patients will complete daily worst abdominal pain (scale 0-10) questionnaires throughout the duration of the study. They will return every 7 days for a total of 4 visits for device replacement and additional questionnaires, including the IBS-SSS. Four devices will be placed in total (start of weeks 1, 2, 3, and 4). Stimulation time is 5 days/week during each of the 4 consecutive weeks. Additional questionnaires will be completed at the end of week 4 and at extended follow-up (8 weeks).
Sponsors
Innovative Health Solutions
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Masking description
Patients who meet study eligibility criteria will be randomly assigned (1:1) in blocks of two and four, using a code generated by a randomization program to 4 weeks of stimulation with an active or inactive (sham) PENFS device. Per manufacturer design, both active stimulation and sham are below a detectable sensation threshold. Allocation will be concealed, and all physicians, statisticians, participants, and research coordinators will be unaware of device codes. One research coordinator who has no patient contact will be unblinded and handle allocation and storage of devices. At the end of 4 weeks, patients will be asked to which device arm they believe they were randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Adults, aged 18-60 years, who are able to provide written, informed consent. * Patients must meet Rome IV criteria for IBS, confirmed by a gastroenterologist who specializes in functional GI disorders. Any of the IBS bowel habit subtypes (diarrhea, constipation, mixed bowel habits, unclassified) will be allowed. * Average daily worst abdominal pain score between 4 and 8 (on a 0-10-point rating scale). * Minimum of 2 days of abdominal pain/week prior to starting trial. * At least moderate IBS symptom severity with an IBS-SSS of at least 175 (total score range 0-500). * If receiving pharmacologic therapy for abdominal pain associated with IBS, doses must be stable for at least 60 days prior to enrollment in the trial. * If receiving pharmacologic therapy for IBS that does not have an effect on abdominal pain, doses must be stable for at least 30 days prior to enrollment in the trial. Mandatory
Exclusion criteria
* Patients under the age of 18 years or over the age of 60 years * Patients who cannot provide informed consent or do not speak English * Co-morbid, organic medical conditions associated with abdominal pain, including: Inflammatory bowel disease, chronic liver disease, peptic ulcer disease, celiac disease, diverticulitis, appendicitis, colorectal cancer, endometriosis, pregnancy, other intestinal or extra-intestinal malignancies. Patients with overlapping functional GI disorders (i.e. functional dyspepsia) will not be excluded as long as IBS is their predominant disorder * History of surgery involving CN V, VII, IX, or X. * History of abdominal surgeries other than appendectomy or cholecystectomy at least 6 months before entry into trial. * Patients on chronic opioids, benzodiazepines, or with illicit substance use * Patients with underlying neurologic conditions, including history of: seizures, CVA, uncontrolled migraines, traumatic brain injury, multiple sclerosis * Patients with underlying psychiatric conditions * Patients with dermatologic conditions affecting the ear, face, or neck region (i.e. psoriasis), or with cuts or abrasions to the external ear that would interfere with needle placement * Patients with hemophilia or other bleeding disorders * Patients with any implanted electrical device * Patients who are pregnant or breastfeeding Preferred, but not mandatory,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in IBS Symptom Severity From Baseline | 4 weeks, 8 weeks. | To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment and at extended follow-up (8 weeks), assessed through a mean change in the IBS-SSS between groups. Answers were measured using the IBS-SSS. Higher scores indicate worse symptoms. The score range is 0-500. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IBS Symptom Severity Responder Rate | Week 4 | To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment compared to baseline. Participants will be considered responders if there is at least a 50-point reduction on the IBS-SSS. |
| Mean Change in Average Daily Worst Abdominal Pain From Baseline | Week 4 | To compare the efficacy of PENFS therapy versus sham therapy on mean worst daily abdominal pain scores after 4 weeks compared to baseline in adult patients with IBS. The scale is measured as follows, with higher scores indicating worse pain: Daily Worse Abdominal Pain Severity: • How would you rate your worst abdominal pain over the past 24-hours (0-10)? o 0 = no pain, 10= worst pain possible |
| Change in Average Daily Stool Consistency From Baseline | Week 4 | To compare the efficacy of PENFS therapy versus sham therapy on the change in average daily stool consistency after 4 weeks of treatment compared to baseline, assessed using the Bristol Stool Form Scale (BSFS) (stool types 1-7; types 1 and 2 indicate constipation, types 3 and 4 are normal consistency stools, type 5 indicates stool lacking fiber, types 6 and 7 indicate diarrhea). |
| Change in Average Weekly Bowel Habits From Baseline | Week 4, week 8 | To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bowel habits after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Constipation Scale (percentiles 0.3-100%; higher percentiles indicate greater constipation). |
| Change in Quality of Life From Baseline | Week 4, week 8 | To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS-quality of life (IBS-QOL) in adult patients with IBS after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline. IBS QOL will be assessed on a scale from 0-100, with higher scores indicating better IBS specific quality of life. |
| Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | 4 weeks | Same measures as outcome measure 12. LF peak FFT: Peak frequency within the low-frequency range (typically 0.04-0.15 Hz) of the HRV spectrum HF peak FFT: Peak frequency within the high-frequency range (typically 0.15-0.4 Hz) of the HRV spectrum. VLF peak AR: Peak frequency within the very-low-frequency range (typically 0.0033-0.04 Hz) of the HRV spectrum. HF peak AR: Peak frequency within the high-frequency range of the HRV spectrum. LF peak AR: Peak frequency within the low-frequency range of the HRV spectrum. |
| Change in Average Weekly Bloating Symptoms From Baseline | 4 weeks, 8 weeks | To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bloating symptoms at 4 weeks and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Gas and Bloating Scale (percentiles 0.1-100%; higher percentiles indicate greater gas and bloating). |
| Change in Average Weekly Abdominal Pain Symptoms From Baseline | 4 weeks, 8 weeks | To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly abdominal pain symptoms at 4 weeks and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Belly Pain Scale (percentiles 2-100%; higher percentiles indicate worse abdominal pain). |
| Chang in Average Weekly Bowel Habits From Baseline | 4 weeks, 8 weeks | To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bowel habits after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Diarrhea Scale (percentiles 1-100%; higher percentiles indicate greater diarrhea). |
| Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | Baseline | LF peak FFT: Peak frequency within the low-frequency range (typically 0.04-0.15 Hz) of the HRV spectrum, as determined by Fast Fourier Transform (FFT) analysis. HF peak FFT: Represents the peak frequency within the high-frequency range (typically 0.15-0.4 Hz) of the HRV spectrum, as determined by FFT analysis. VLF peak AR: Represents the peak frequency within the very-low-frequency range (typically 0.0033-0.04 Hz) of the HRV spectrum, as determined by autoregressive (AR) modeling. HF peak AR: Represents the peak frequency within the high-frequency range of the HRV spectrum, as determined by AR modeling. LF peak AR: Represents the peak frequency within the low-frequency range of the HRV spectrum, as det |
| Number of Participants With Treatment-related Adverse Events as Assessed by a Weekly Adverse Events Questionnaire | Week 4 | To compare the incidence of treatment-related adverse events from PENFS therapy versus sham therapy in adult patients with IBS. Adverse events will be assessed by a weekly adverse events questionnaire that determines the severity of the adverse event, the relationship to the study intervention, the action taken regarding the study intervention, the outcome of the adverse event, whether or not the adverse event was expected, and if the event was considered a serious adverse event (SAE). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device The PENFS device has a battery activated generator and wire harness. Four leads are attached to the generator, each with a sterile 2 mm, titanium needle. The patient's ear is trans-illuminated to identify neurovascular bundles that are avoided during needle placement. The generator is attached with adhesive to the skin behind the patient's ear. Needles are inserted into the dorsal and ventral aspects of the ear, within 1-1.5 mm of the vascular branches to create a field effect. The device settings are standardized and deliver 3.2 volts with alternating frequencies (1 ms pulses of 1 Hz and 10 Hz) every 2 s. | 7 |
| Sham Device The sham devices will be identical to the active devices but will not administer electrical charges. Per manufacturer design and patient anecdotal experience from previous studies, both active stimulation and sham are below detectable sensation threshold. Per report from previous studies, some patients may experience a sensation around the ear after percutaneous needle placement; however, this sensation can occur with equal likelihood in the active or sham device. The device is worn for 5 days a week for a total of 4 weeks. Patients remove devices at home on day 6 of each treatment cycle. Patients will also be asked to wear a SmartWatch as above. | 8 |
| Total | 15 |
Baseline characteristics
| Characteristic | Peripheral Electrical Nerve Field Stimulation (PENFS) Device | Sham Device | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 8 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 9 Participants |
| Region of Enrollment United States | 7 participants | 8 participants | 15 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Mean Change in IBS Symptom Severity From Baseline
To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment and at extended follow-up (8 weeks), assessed through a mean change in the IBS-SSS between groups. Answers were measured using the IBS-SSS. Higher scores indicate worse symptoms. The score range is 0-500.
Time frame: 4 weeks, 8 weeks.
Population: 7 with device, 8 with sham.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean Change in IBS Symptom Severity From Baseline | 4 weeks | 280 score on a scale | Standard Deviation 39.9 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean Change in IBS Symptom Severity From Baseline | 8 weeks | 244 score on a scale | Standard Deviation 122 |
| Sham Device | Mean Change in IBS Symptom Severity From Baseline | 4 weeks | 320 score on a scale | Standard Deviation 91.7 |
| Sham Device | Mean Change in IBS Symptom Severity From Baseline | 8 weeks | 316 score on a scale | Standard Deviation 76.5 |
Secondary
Change in Average Daily Stool Consistency From Baseline
To compare the efficacy of PENFS therapy versus sham therapy on the change in average daily stool consistency after 4 weeks of treatment compared to baseline, assessed using the Bristol Stool Form Scale (BSFS) (stool types 1-7; types 1 and 2 indicate constipation, types 3 and 4 are normal consistency stools, type 5 indicates stool lacking fiber, types 6 and 7 indicate diarrhea).
Time frame: Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Average Daily Stool Consistency From Baseline | 2.91 score on a scale | Standard Deviation 1.1 |
| Sham Device | Change in Average Daily Stool Consistency From Baseline | 3.78 score on a scale | Standard Deviation 2.39 |
Secondary
Change in Average Weekly Abdominal Pain Symptoms From Baseline
To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly abdominal pain symptoms at 4 weeks and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Belly Pain Scale (percentiles 2-100%; higher percentiles indicate worse abdominal pain).
Time frame: 4 weeks, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Average Weekly Abdominal Pain Symptoms From Baseline | 8 weeks | 62.8 score on a scale | Standard Deviation 9.92 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Average Weekly Abdominal Pain Symptoms From Baseline | 4 weeks | 65.8 score on a scale | Standard Deviation 4.72 |
| Sham Device | Change in Average Weekly Abdominal Pain Symptoms From Baseline | 4 weeks | 69.4 score on a scale | Standard Deviation 3.82 |
| Sham Device | Change in Average Weekly Abdominal Pain Symptoms From Baseline | 8 weeks | 69.3 score on a scale | Standard Deviation 2.53 |
Secondary
Change in Average Weekly Bloating Symptoms From Baseline
To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bloating symptoms at 4 weeks and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Gas and Bloating Scale (percentiles 0.1-100%; higher percentiles indicate greater gas and bloating).
Time frame: 4 weeks, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Average Weekly Bloating Symptoms From Baseline | 4 weeks | 58.2 score on a scale | Standard Deviation 8.11 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Average Weekly Bloating Symptoms From Baseline | 8 weeks | 56.7 score on a scale | Standard Deviation 8.56 |
| Sham Device | Change in Average Weekly Bloating Symptoms From Baseline | 4 weeks | 65.0 score on a scale | Standard Deviation 6.44 |
| Sham Device | Change in Average Weekly Bloating Symptoms From Baseline | 8 weeks | 64.2 score on a scale | Standard Deviation 5.64 |
Secondary
Change in Average Weekly Bowel Habits From Baseline
To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bowel habits after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Constipation Scale (percentiles 0.3-100%; higher percentiles indicate greater constipation).
Time frame: Week 4, week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Average Weekly Bowel Habits From Baseline | week 4 | 51.5 score on a scale | Standard Deviation 9.11 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Average Weekly Bowel Habits From Baseline | week 8 | 53.8 score on a scale | Standard Deviation 6.43 |
| Sham Device | Change in Average Weekly Bowel Habits From Baseline | week 4 | 62.8 score on a scale | Standard Deviation 3.93 |
| Sham Device | Change in Average Weekly Bowel Habits From Baseline | week 8 | 61.3 score on a scale | Standard Deviation 4.74 |
Secondary
Change in Quality of Life From Baseline
To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS-quality of life (IBS-QOL) in adult patients with IBS after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline. IBS QOL will be assessed on a scale from 0-100, with higher scores indicating better IBS specific quality of life.
Time frame: Week 4, week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Quality of Life From Baseline | week 4 | 66.8 score on a scale | Standard Deviation 20.4 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Change in Quality of Life From Baseline | week 8 | 42.3 score on a scale | Standard Deviation 22.7 |
| Sham Device | Change in Quality of Life From Baseline | week 4 | 42.1 score on a scale | Standard Deviation 19 |
| Sham Device | Change in Quality of Life From Baseline | week 8 | 74.7 score on a scale | Standard Deviation 20.3 |
Secondary
Chang in Average Weekly Bowel Habits From Baseline
To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bowel habits after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Diarrhea Scale (percentiles 1-100%; higher percentiles indicate greater diarrhea).
Time frame: 4 weeks, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Chang in Average Weekly Bowel Habits From Baseline | 4 weeks | 59.9 score on a scale | Standard Deviation 8.15 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Chang in Average Weekly Bowel Habits From Baseline | 8 weeks | 50.8 score on a scale | Standard Deviation 9.31 |
| Sham Device | Chang in Average Weekly Bowel Habits From Baseline | 4 weeks | 63.4 score on a scale | Standard Deviation 5.92 |
| Sham Device | Chang in Average Weekly Bowel Habits From Baseline | 8 weeks | 54.8 score on a scale | Standard Deviation 14 |
Secondary
IBS Symptom Severity Responder Rate
To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment compared to baseline. Participants will be considered responders if there is at least a 50-point reduction on the IBS-SSS.
Time frame: Week 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | IBS Symptom Severity Responder Rate | 3 Participants |
| Sham Device | IBS Symptom Severity Responder Rate | 2 Participants |
Secondary
Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks.
HF/LF ratio AR: Ratio of high-frequency to low-frequency ratio in heart rate variability (HRV) analysis, as determined by AR. It reflects the balance between parasympathetic (HF) and sympathetic (LF) nervous system activity influencing heart rate. HF/LF ratio FFT: Ratio of high-frequency to low-frequency ratio in heart rate variability (HRV) analysis; reflects the balance between parasympathetic (HF) and sympathetic (LF) nervous system activity influencing heart rate.
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | LF_HF_ratio_FFT_ACT_Wk_4 | 2.83 ratio | Standard Deviation 4.32 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | LF_HF_ratio_AR_ACT_Wk_4 | 2.21 ratio | Standard Deviation 3.18 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | LF_HF_ratio_FFT_ACT_Wk_4 | 0.574 ratio | Standard Deviation 0.0332 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | LF_HF_ratio_AR_ACT_Wk_4 | 0.592 ratio | Standard Deviation 0.128 |
Secondary
Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks.
Same measures as outcome measure 12. LF peak FFT: Peak frequency within the low-frequency range (typically 0.04-0.15 Hz) of the HRV spectrum HF peak FFT: Peak frequency within the high-frequency range (typically 0.15-0.4 Hz) of the HRV spectrum. VLF peak AR: Peak frequency within the very-low-frequency range (typically 0.0033-0.04 Hz) of the HRV spectrum. HF peak AR: Peak frequency within the high-frequency range of the HRV spectrum. LF peak AR: Peak frequency within the low-frequency range of the HRV spectrum.
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | HFpeak_FFT_Hz_ACT_Wk_4 | 0.296 Hz | Standard Deviation 0.0263 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | LFpeak_AR_Hz_ACT_Wk_4 | 0.0975 Hz | Standard Deviation 0.0357 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | VLFpeak_AR_Hz_ACT_Wk_4 | 0.0400 Hz | Standard Deviation 0 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | HFpeak_AR_Hz_ACT_Wk_4 | 0.298 Hz | Standard Deviation 0.0357 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | LFpeak_FFT_Hz_ACT_Wk_4 | 0.0817 Hz | Standard Deviation 0.0454 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | HFpeak_AR_Hz_ACT_Wk_4 | 0.294 Hz | Standard Deviation 0.0483 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | LFpeak_FFT_Hz_ACT_Wk_4 | 0.103 Hz | Standard Deviation 0.0115 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | HFpeak_FFT_Hz_ACT_Wk_4 | 0.287 Hz | Standard Deviation 0.0555 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | VLFpeak_AR_Hz_ACT_Wk_4 | 0.0278 Hz | Standard Deviation 0.0212 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks. | LFpeak_AR_Hz_ACT_Wk_4 | 0.0833 Hz | Standard Deviation 0.0393 |
Secondary
Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline.
LF peak FFT: Peak frequency within the low-frequency range (typically 0.04-0.15 Hz) of the HRV spectrum, as determined by Fast Fourier Transform (FFT) analysis. HF peak FFT: Represents the peak frequency within the high-frequency range (typically 0.15-0.4 Hz) of the HRV spectrum, as determined by FFT analysis. VLF peak AR: Represents the peak frequency within the very-low-frequency range (typically 0.0033-0.04 Hz) of the HRV spectrum, as determined by autoregressive (AR) modeling. HF peak AR: Represents the peak frequency within the high-frequency range of the HRV spectrum, as determined by AR modeling. LF peak AR: Represents the peak frequency within the low-frequency range of the HRV spectrum, as det
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | HFpeak_FFT_Hz_ACT_Ba | 0.219 Hz | Standard Deviation 0.0489 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | LFpeak_AR_Hz_ACT_Ba | 0.119 Hz | Standard Deviation 0.0345 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | VLFpeak_AR_Hz_ACT_Ba | 0.0400 Hz | Standard Deviation 0 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | HFpeak_AR_Hz_ACT_Ba | 0.213 Hz | Standard Deviation 0.0516 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | LFpeak_FFT_Hz_ACT_Ba | 0.0822 Hz | Standard Deviation 0.0217 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | HFpeak_AR_Hz_ACT_Ba | 0.214 Hz | Standard Deviation 0.0508 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | LFpeak_FFT_Hz_ACT_Ba | 0.0913 Hz | Standard Deviation 0.04 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | HFpeak_FFT_Hz_ACT_Ba | 0.197 Hz | Standard Deviation 0.0258 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | VLFpeak_AR_Hz_ACT_Ba | 0.0253 Hz | Standard Deviation 0.0201 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | LFpeak_AR_Hz_ACT_Ba | 0.0787 Hz | Standard Deviation 0.045 |
Secondary
Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline.
HF/LF ratio FFT: Ratio of high-frequency to low-frequency ratio in heart rate variability (HRV) analysis, as determined by FFT analysis. It reflects the balance between parasympathetic (HF) and sympathetic (LF) nervous system activity influencing heart rate. HF/LF ratio ACT: Ratio of high-frequency to low-frequency ratio in heart rate variability (HRV) analysis, as determined by AR modeling. It reflects the balance between parasympathetic (HF) and sympathetic (LF) nervous system activity influencing heart rate.
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | LF_HF_ratio_FFT_ACT_Ba | 1.26 ratio | Standard Deviation 2.3 |
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | LF_HF_ratio_AR_ACT_Ba | 1.70 ratio | Standard Deviation 3.09 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | LF_HF_ratio_FFT_ACT_Ba | 6.66 ratio | Standard Deviation 13.33 |
| Sham Device | Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline. | LF_HF_ratio_AR_ACT_Ba | 5.13 ratio | Standard Deviation 9.86 |
Secondary
Mean Change in Average Daily Worst Abdominal Pain From Baseline
To compare the efficacy of PENFS therapy versus sham therapy on mean worst daily abdominal pain scores after 4 weeks compared to baseline in adult patients with IBS. The scale is measured as follows, with higher scores indicating worse pain: Daily Worse Abdominal Pain Severity: • How would you rate your worst abdominal pain over the past 24-hours (0-10)? o 0 = no pain, 10= worst pain possible
Time frame: Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Mean Change in Average Daily Worst Abdominal Pain From Baseline | 5.02 score on a scale | Standard Deviation 1.84 |
| Sham Device | Mean Change in Average Daily Worst Abdominal Pain From Baseline | 5.03 score on a scale | Standard Deviation 1.61 |
Secondary
Number of Participants With Treatment-related Adverse Events as Assessed by a Weekly Adverse Events Questionnaire
To compare the incidence of treatment-related adverse events from PENFS therapy versus sham therapy in adult patients with IBS. Adverse events will be assessed by a weekly adverse events questionnaire that determines the severity of the adverse event, the relationship to the study intervention, the action taken regarding the study intervention, the outcome of the adverse event, whether or not the adverse event was expected, and if the event was considered a serious adverse event (SAE).
Time frame: Week 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Peripheral Electrical Nerve Field Stimulation (PENFS) Device and Sham Device | Number of Participants With Treatment-related Adverse Events as Assessed by a Weekly Adverse Events Questionnaire | 0 Participants |
| Sham Device | Number of Participants With Treatment-related Adverse Events as Assessed by a Weekly Adverse Events Questionnaire | 0 Participants |