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A Study of Randomized Sham-control Auricular TENS Unit Stimulation in Pediatric Functional Gastrointestinal Disorders

Primary Purpose

Functional Gastrointestinal Disorders, Vagus Nerve Autonomic Disorder, Irritable Bowel Syndrome

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcutaneous Electrical Nerve Stimulation (TENS)
Sham Transcutaneous Electrical Nerve Stimulation
Sponsored by
Gisela Grotewold Chelimsky
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Functional Gastrointestinal Disorders

Eligibility Criteria

12 Years - 18 Years (Child, Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Female patients 12-18 years old with chronic idiopathic nausea, function abdominal pain, dyspepsia and/or irritable bowel syndrome
  • English Speaking

Exclusion Criteria:

  • Patients who are unable to stand upright during the heart rate variability recording
  • Patients with a known bleeding disorder
  • Gastric or cardiac pacer or defibrillator
  • Poor circulation in lower limbs
  • Swollen or inflamed outer ear
  • Epilepsy
  • Abdominal or inguinal hernia
  • Any unstable medical condition, such as renal disease, uncontrolled diabetes, etc.
  • Requires new medication during the 8 weeks of the study that may affect gastrointestinal symptoms, vagal modulation or immune response
  • Inability to answer questionnaires or repoty pain in a 0-10 visual analog scale.

Sites / Locations

  • Virginia Commonwealth University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active Stimulation (8)

Sham Stimulation (4), Active (4)

Arm Description

Participants will receive active auricular microstimulation via TENS unit for 8 weeks. Under guidance from the study team, participants will self-administer the TENS therapy for two 1-hour periods a day for 8 weeks.

Participants will receive sham therapy via inactive TENS unit for 4 weeks, followed by active auricular microstimulation via TENS for 4 weeks. Under guidance from the study team, participants will self-administer the TENS therapy for two 1-hour periods a day for 8 weeks (4 weeks of therapy with inactive TENS, 4 weeks with active TENS).

Outcomes

Primary Outcome Measures

Change in Heart Rate Variability at 4 Weeks
EKG tracing will be used to analyze Heart Rate Variability as an indirect measure of vagal nerve output and central autonomic control.
Change in Heart Rate Variability at 8 Weeks
EKG tracing will be used to analyze Heart Rate Variability as an indirect measure of vagal nerve output and central autonomic control.
Change in Mitochondrial Bioenergetics Measured by Basal Oxygen Consumption Rate at 4 Weeks (Basal Consumption)
Blood draw will be tested for mitochondrial function by Seahorse assay, which measures Basal Oxygen Consumption Rate of live cells to provide insight into mitochondrial activity.
Change in Mitochondrial Bioenergetics Measured by Basal Oxygen Consumption Rate at 8 Weeks (Basal Consumption)
Blood draw will be tested for mitochondrial function by Seahorse assay, which measures Basal Oxygen Consumption Rate of live cells to provide insight into mitochondrial activity.
Change in Blood Cytokines Measured by TNF α Levels at 4 Weeks
Blood will be analyzed to detect changes in protein cytokine TNF α levels, an indicator for inflammation.
Change in Blood Cytokines Measured by TNF α Levels at 8 Weeks
Blood will be analyzed to detect changes in protein cytokine TNF α levels, an indicator for inflammation

Secondary Outcome Measures

Change From Baseline in Functional Disability Inventory (Child and Adolescent)
The Functional Disability Inventory (FDI) Child and Adolescent questionnaire will be used to assess change in symptoms. Participants will rank physical trouble or difficulty completing 15 different daily activities (Eating regular meals, Being at school all day, Walking up stairs, etc.) on a scale of 0-4 for each item (0-No trouble, 1- A Little Trouble, 2- Some Trouble, 3- A Lot of Trouble, 4- Impossible). Higher total scores indicate more difficulty functioning due to physical health, based on a sum score of each item. Sum score interpretation cutoffs include: No/Minimal Disability (0-12), Mild Disability (13-20), Moderate Disability (21-29) and Severe Disability (≥30).
Change From Baseline in Symptom Intensity Questionnaire
Symptom Intensity Questionnaire score will be used to identify the most prominent 5 complaints, with intensity rated on a 10-point centimeter Likert scale. Participants write up to 5 of their most severe symptoms, and then rate those symptoms' severity from none (0) to worst you can possibly imagine (10) by placing a vertical line on the scale. Higher symptom ratings reflect higher symptom intensity & frequency. A 1-3 frequency level is a minimum level and indicates symptoms are occasional. A 4-6 frequency is a moderate level, meaning that symptoms are intermittent, coming and going. A 7-8 frequency is an indication that the symptoms are present more often than not but still not constant. A 9-10 frequency level is severe and indicates that symptoms are constant. The electronic data capture system's field validation used during the study automatically translated the participant-facing 0-10 slider scale placement into a score of 0-100, hence the reported mean values of over 10.
Change From Baseline in Pain Catastrophizing Scale (Child)
The Pain Catastrophizing Scale Child form (PCS-C) will be completed by the participant. The PCS-C is a modification of the adult Pain Catastrophizing Scale for use in children, measuring pain-related cognitions and the dimensions of helplessness, rumination and magnification. Participants rate how strong their feelings are about pain on a 5 point scale (0- Not at all, 1- To a slight degree, 2- To a moderate degree, 3- To a great degree, 4- All the time). Sum scores range from 0-52. Higher scores indicate higher levels of pain catastrophizing. A total PCS score of 30 represents a clinically relevant level of catastrophizing.
Change From Baseline in Revised Child Anxiety and Depression Scale
The Revised Child Anxiety and Depression Scale (RCADS) assesses children grades 3 to 12 containing subscales assessing for symptoms of anxiety and depression. Participants rate frequency of occurrences described in the items on a 4 point scale (0- Never, 1- Sometimes, 2- Often, or 3- Always). Sum scores of anxiety/depression items were assessed. Depression items: score range 0-30 Anxiety items: score range 0-18 Higher scores on both the depression & anxiety items indicate higher levels of depression & anxiety. Raw sum scores of both the depression & anxiety subscale items are translated to a T-score. T-scores below 65 represent low severity. T-scores between 65-70 represent medium severity and are on the borderline clinical threshold. T-scores above 70 represent high severity and are above the clinical threshold. A T-score of 50 indicates the population mean with a standard deviation of 10.
Change From Baseline in Functional Disability Inventory (Parent)
The Functional Disability Inventory (FDI) Parent questionnaire will be used to assess change in the participants symptoms as rated by the participants parent/guardian. Parents will rank their child's physical trouble or difficulty completing 15 different daily activities (Eating regular meals, Being at school all day, Walking up stairs, etc.) on a scale of 0-4 for each item (0-No trouble, 1- A Little Trouble, 2- Some Trouble, 3- A Lot of Trouble, 4- Impossible). Higher total scores indicate more difficulty functioning due to physical health, based on a sum score of each item. Sum score interpretation cutoffs include: No/Minimal Disability (0-12), Mild Disability (13-20), Moderate Disability (21-29) and Severe Disability (≥30).
Change From Baseline in Pain Catastrophizing Scale (Parent)
The Pain Catastrophizing Scale Parent form (PCS-P) will be completed by the parent or guardian of the participant. The PCS-P is a proxy questionnaire to the PCS-C, measuring the feelings the parent has when their child is in pain. Parents rate how strongly they feel when their child is in pain on a 5 point scale (0- Not at all, 1- To a slight degree, 2- To a moderate degree, 3- To a great degree, 4- All the time). Sum scores range from 0-52. Higher scores indicate higher levels of pain catastrophizing. A total PCS score of 30 represents a clinically relevant level of catastrophizing.

Full Information

First Posted
January 22, 2020
Last Updated
October 10, 2023
Sponsor
Gisela Grotewold Chelimsky
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1. Study Identification

Unique Protocol Identification Number
NCT04247100
Brief Title
A Study of Randomized Sham-control Auricular TENS Unit Stimulation in Pediatric Functional Gastrointestinal Disorders
Official Title
A Pilot Study of a Randomized Sham-control Auricular TENS Unit Stimulation to Improve Symptoms Through Vagal Modulation in Pediatric Functional Gastrointestinal Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
Funding ended prior to hitting the enrollment goal
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
August 23, 2021 (Actual)
Study Completion Date
August 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Gisela Grotewold Chelimsky

4. Oversight

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.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to see if using a micro-current through a device called a TENS (Transcutaneous Electrical Nerve Stimulator) unit helps to improve functional gastrointestinal disorder (FGID) symptoms in children by stimulation of the vagus nerve. The study will compare two methods of stimulation to determine if there is a difference in the two methods.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Functional Gastrointestinal Disorders, Vagus Nerve Autonomic Disorder, Irritable Bowel Syndrome, Nausea, Dyspepsia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
30 participants will be enrolled in this double-blind sham control study. Fifteen participants will undergo sham stimulation for 4 weeks followed by active microstimulation for 4 weeks. The other 15 participants will have active microstimulation for all 8 weeks.
Masking
ParticipantCare Provider
Masking Description
Participants will be sent home at baseline with a TENS unit and a sealed envelope with instructions for device settings. The envelope will contain instructions for either sham stimulation or active stimulation (unknown to the performing coordinator and participant). Both groups will receive a new device and another set of instructions from the study team at 4 weeks. It is possible and permitted that the performing study coordinator will become aware of which group the subject is in when checking in on the subject.
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active Stimulation (8)
Arm Type
Experimental
Arm Description
Participants will receive active auricular microstimulation via TENS unit for 8 weeks. Under guidance from the study team, participants will self-administer the TENS therapy for two 1-hour periods a day for 8 weeks.
Arm Title
Sham Stimulation (4), Active (4)
Arm Type
Sham Comparator
Arm Description
Participants will receive sham therapy via inactive TENS unit for 4 weeks, followed by active auricular microstimulation via TENS for 4 weeks. Under guidance from the study team, participants will self-administer the TENS therapy for two 1-hour periods a day for 8 weeks (4 weeks of therapy with inactive TENS, 4 weeks with active TENS).
Intervention Type
Device
Intervention Name(s)
Transcutaneous Electrical Nerve Stimulation (TENS)
Other Intervention Name(s)
InTENSity Select Combo by Roscoe Medical
Intervention Description
Active Transcutaneous Auricular Microstimulation delivered by TENS device
Intervention Type
Device
Intervention Name(s)
Sham Transcutaneous Electrical Nerve Stimulation
Other Intervention Name(s)
InTENSity Select Combo by Roscoe Medical (Inactive)
Intervention Description
Sham therapy will be delivered by applying the TENS device with non-conductive electrodes so that no microstimulation is delivered
Primary Outcome Measure Information:
Title
Change in Heart Rate Variability at 4 Weeks
Description
EKG tracing will be used to analyze Heart Rate Variability as an indirect measure of vagal nerve output and central autonomic control.
Time Frame
Assessed at baseline, week 4, and week 8. Change in baseline to week 4 is reported.
Title
Change in Heart Rate Variability at 8 Weeks
Description
EKG tracing will be used to analyze Heart Rate Variability as an indirect measure of vagal nerve output and central autonomic control.
Time Frame
Assessed at baseline, week 4, and week 8. Change in baseline to week 8 is reported.
Title
Change in Mitochondrial Bioenergetics Measured by Basal Oxygen Consumption Rate at 4 Weeks (Basal Consumption)
Description
Blood draw will be tested for mitochondrial function by Seahorse assay, which measures Basal Oxygen Consumption Rate of live cells to provide insight into mitochondrial activity.
Time Frame
Assessed at baseline, week 4, and week 8. Change in baseline to week 4 is reported.
Title
Change in Mitochondrial Bioenergetics Measured by Basal Oxygen Consumption Rate at 8 Weeks (Basal Consumption)
Description
Blood draw will be tested for mitochondrial function by Seahorse assay, which measures Basal Oxygen Consumption Rate of live cells to provide insight into mitochondrial activity.
Time Frame
Assessed at baseline, week 4, and week 8. Change in baseline to week 8 is reported.
Title
Change in Blood Cytokines Measured by TNF α Levels at 4 Weeks
Description
Blood will be analyzed to detect changes in protein cytokine TNF α levels, an indicator for inflammation.
Time Frame
Assessed at baseline, week 4, and week 8. Change in baseline to week 4 is reported.
Title
Change in Blood Cytokines Measured by TNF α Levels at 8 Weeks
Description
Blood will be analyzed to detect changes in protein cytokine TNF α levels, an indicator for inflammation
Time Frame
Assessed at baseline, week 4, and week 8. Change in baseline to week 8.
Secondary Outcome Measure Information:
Title
Change From Baseline in Functional Disability Inventory (Child and Adolescent)
Description
The Functional Disability Inventory (FDI) Child and Adolescent questionnaire will be used to assess change in symptoms. Participants will rank physical trouble or difficulty completing 15 different daily activities (Eating regular meals, Being at school all day, Walking up stairs, etc.) on a scale of 0-4 for each item (0-No trouble, 1- A Little Trouble, 2- Some Trouble, 3- A Lot of Trouble, 4- Impossible). Higher total scores indicate more difficulty functioning due to physical health, based on a sum score of each item. Sum score interpretation cutoffs include: No/Minimal Disability (0-12), Mild Disability (13-20), Moderate Disability (21-29) and Severe Disability (≥30).
Time Frame
Assessed at baseline, week 4, and week 8. Score changes from baseline to week 4 and baseline to week 8 are reported.
Title
Change From Baseline in Symptom Intensity Questionnaire
Description
Symptom Intensity Questionnaire score will be used to identify the most prominent 5 complaints, with intensity rated on a 10-point centimeter Likert scale. Participants write up to 5 of their most severe symptoms, and then rate those symptoms' severity from none (0) to worst you can possibly imagine (10) by placing a vertical line on the scale. Higher symptom ratings reflect higher symptom intensity & frequency. A 1-3 frequency level is a minimum level and indicates symptoms are occasional. A 4-6 frequency is a moderate level, meaning that symptoms are intermittent, coming and going. A 7-8 frequency is an indication that the symptoms are present more often than not but still not constant. A 9-10 frequency level is severe and indicates that symptoms are constant. The electronic data capture system's field validation used during the study automatically translated the participant-facing 0-10 slider scale placement into a score of 0-100, hence the reported mean values of over 10.
Time Frame
Assessed at baseline, week 4, and week 8. Changes per symptom score in baseline to week 4 and baseline to week 8 are reported.
Title
Change From Baseline in Pain Catastrophizing Scale (Child)
Description
The Pain Catastrophizing Scale Child form (PCS-C) will be completed by the participant. The PCS-C is a modification of the adult Pain Catastrophizing Scale for use in children, measuring pain-related cognitions and the dimensions of helplessness, rumination and magnification. Participants rate how strong their feelings are about pain on a 5 point scale (0- Not at all, 1- To a slight degree, 2- To a moderate degree, 3- To a great degree, 4- All the time). Sum scores range from 0-52. Higher scores indicate higher levels of pain catastrophizing. A total PCS score of 30 represents a clinically relevant level of catastrophizing.
Time Frame
Assessed at baseline, week 4, and week 8. Score change in baseline to week 8 is reported.
Title
Change From Baseline in Revised Child Anxiety and Depression Scale
Description
The Revised Child Anxiety and Depression Scale (RCADS) assesses children grades 3 to 12 containing subscales assessing for symptoms of anxiety and depression. Participants rate frequency of occurrences described in the items on a 4 point scale (0- Never, 1- Sometimes, 2- Often, or 3- Always). Sum scores of anxiety/depression items were assessed. Depression items: score range 0-30 Anxiety items: score range 0-18 Higher scores on both the depression & anxiety items indicate higher levels of depression & anxiety. Raw sum scores of both the depression & anxiety subscale items are translated to a T-score. T-scores below 65 represent low severity. T-scores between 65-70 represent medium severity and are on the borderline clinical threshold. T-scores above 70 represent high severity and are above the clinical threshold. A T-score of 50 indicates the population mean with a standard deviation of 10.
Time Frame
Assessed at baseline, week 4, and week 8. Changes in generalized anxiety & depression t-scores (translated from raw subscale scores) in baseline to week 4 and baseline to week 8 are reported.
Title
Change From Baseline in Functional Disability Inventory (Parent)
Description
The Functional Disability Inventory (FDI) Parent questionnaire will be used to assess change in the participants symptoms as rated by the participants parent/guardian. Parents will rank their child's physical trouble or difficulty completing 15 different daily activities (Eating regular meals, Being at school all day, Walking up stairs, etc.) on a scale of 0-4 for each item (0-No trouble, 1- A Little Trouble, 2- Some Trouble, 3- A Lot of Trouble, 4- Impossible). Higher total scores indicate more difficulty functioning due to physical health, based on a sum score of each item. Sum score interpretation cutoffs include: No/Minimal Disability (0-12), Mild Disability (13-20), Moderate Disability (21-29) and Severe Disability (≥30).
Time Frame
Assessed at baseline, week 4, and week 8. Score changes from baseline to week 4 and baseline to week 8 are reported.
Title
Change From Baseline in Pain Catastrophizing Scale (Parent)
Description
The Pain Catastrophizing Scale Parent form (PCS-P) will be completed by the parent or guardian of the participant. The PCS-P is a proxy questionnaire to the PCS-C, measuring the feelings the parent has when their child is in pain. Parents rate how strongly they feel when their child is in pain on a 5 point scale (0- Not at all, 1- To a slight degree, 2- To a moderate degree, 3- To a great degree, 4- All the time). Sum scores range from 0-52. Higher scores indicate higher levels of pain catastrophizing. A total PCS score of 30 represents a clinically relevant level of catastrophizing.
Time Frame
Assessed at baseline, week 4, and week 8. Score change from baseline to week 8 is reported.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female patients 12-18 years old with chronic idiopathic nausea, function abdominal pain, dyspepsia and/or irritable bowel syndrome English Speaking Exclusion Criteria: Patients who are unable to stand upright during the heart rate variability recording Patients with a known bleeding disorder Gastric or cardiac pacer or defibrillator Poor circulation in lower limbs Swollen or inflamed outer ear Epilepsy Abdominal or inguinal hernia Any unstable medical condition, such as renal disease, uncontrolled diabetes, etc. Requires new medication during the 8 weeks of the study that may affect gastrointestinal symptoms, vagal modulation or immune response Inability to answer questionnaires or report pain on a 0-10 visual analog scale.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gisela Chelimsky, MD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23284
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28826627
Citation
Kovacic K, Hainsworth K, Sood M, Chelimsky G, Unteutsch R, Nugent M, Simpson P, Miranda A. Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.
Results Reference
background
PubMed Identifier
27957782
Citation
Brock C, Brock B, Aziz Q, Moller HJ, Pfeiffer Jensen M, Drewes AM, Farmer AD. Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha. Neurogastroenterol Motil. 2017 May;29(5). doi: 10.1111/nmo.12999. Epub 2016 Dec 12.
Results Reference
background
PubMed Identifier
24948120
Citation
Ji RR, Xu ZZ, Gao YJ. Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 2014 Jul;13(7):533-48. doi: 10.1038/nrd4334. Epub 2014 Jun 20.
Results Reference
background

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A Study of Randomized Sham-control Auricular TENS Unit Stimulation in Pediatric Functional Gastrointestinal Disorders

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