Body Versus Machine: Deep Breathing Versus Vagus Stimulation for the Treatment of Fibromyalgia

December 13, 2021 updated by: Charles Ethan Paccione, M.S., M.A.

Body Versus Machine: Motivational Nondirective Resonance Breathing Versus Transcutaneous Vagus Nerve Stimulation in the Treatment of Fibromyalgia

This randomized controlled trial aims to compare the efficacy of two vagal nerve innervation treatments, motivational nondirective resonance breathing and transcutaneous vagus nerve stimulation, on heart rate variability and pain intensity in patients suffering from CWP. This project tests new and potentially effective means of treating a major global and public health concern where prevalence is high, disability is severe, and treatment options are limited.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The primary objective of this randomized controlled trial is to investigate the effects of motivational nondirective resonance breathing (MNRB) and transcutaneous vagus nerve stimulation (tVNS) on autonomic health and pain intensity in participants diagnosed with chronic widespread pain (CWP). Two versions of MNRB and two versions of tVNS will be delivered and practiced by participants at home for two weeks. The primary outcome is photoplethysmography (PPG) measured heart rate variability (HRV). Secondary outcomes are self report numeric rating scale (NRS) pain intensity, FM pain severity and associated parameters, computerized cuff pressure algometry, blood pressure, psychological distress and health related quality of life.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
105

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Oslo, Norway, 0450
        • Oslo University Hospital, Department of Pain Management and Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Confirmatory diagnosis of chronic widespread pain, including fibromyalgia
  • Widespread pain index (WPI) ≥ 7 and symptom severity scale (SSS) score ≥ 5 OR WPI of 4-6 and SSS score ≥ 9
  • Generalized pain in at least 4 of 5 body regions must be present
  • Pain symptoms have been generally present for at least 3 months
  • Average pain intensity ≥ 6 on a 0-10 numerical rating scale, where 0 represents "no pain" and 10 represents the "worst pain imaginable"

Exclusion Criteria:

  • History and/or presence of comorbid severe neurological or psychiatric disorders (e.g., mania, psychosis, suicidality, bipolar/schizophrenia/autism spectrum disorders)
  • Neurodegenerative disorders (e.g., Parkinson´s, Alzheimer´s, Huntington´s disease)
  • Pregnancy or planned pregnancy
  • Planned surgery
  • Eating disorder (e.g., obesity, anorexia nervosa, etc.)
  • Head trauma
  • Migraine
  • Active heart implants (e.g., pacemaker)
  • Active ear implants (e.g., cochlear implant)
  • Individuals who have practiced meditation consistently (for more than 20 min/day) within the last 6 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: tVNS version 1
Transcutaneous vagus nerve stimulation (tVNS) version 1 will be delivered non-invasively via a portable take-home stimulation device which attaches to the concha of the outer ear. Intensity, pulse duration, and frequency is optimised by the participant. Participants will receive a 15-minute stimulation twice a day (once in the morning upon waking and once in the evening before bed) for 2 weeks.
Device: Transcutaneous Vagal Nerve Stimulation (tVNS)
The tVNS system consists of a non-invasive, handheld stimulator and ear electrode that participants wear like an earphone. Intensity, pulse duration, and frequency of the tVNS stimulation is optimized in order to induce signals in thick-myelinated Aβ fibres of the auricular branch of the vagus nerve (ABVN).
Other Names:
  • Vagus Nerve Stimulation
Other: tVNS version 2
Transcutaneous vagus nerve stimulation (tVNS) version 2 will be delivered non-invasively via a portable take-home stimulation device which attaches to the center of the left ear lobe. Intensity, pulse duration, and frequency is optimised by the participant. Participants will receive a 15-minute stimulation twice a day (once in the morning upon waking and once in the evening before bed) for 2 weeks.
Device: Transcutaneous Vagal Nerve Stimulation (tVNS)
The tVNS system consists of a non-invasive, handheld stimulator and ear electrode that participants wear like an earphone. Intensity, pulse duration, and frequency of the tVNS stimulation is optimized in order to induce signals in thick-myelinated Aβ fibres of the auricular branch of the vagus nerve (ABVN).
Other Names:
  • Vagus Nerve Stimulation
Other: MNRB version 1
Motivational nondirective resonance breathing (MNRB) version 1 will be delivered via a take-home guided breathing apparatus. Participants will be guided through a deep breathing session. Participants will practice MNRB version 1 for 15-minutes twice a day (once in the morning upon waking and once in the evening before bed) for 2 weeks.
Other: Motivational nondirective resonance breathing (MNRB)
Motivational nondirective resonance breathing (MNRB) is a type of diaphragmatic breathing technique that trains the body to breathe at resonance frequency with a mental state of open-awareness.
Other Names:
  • Diaphragmatic Breathing
Other: MNRB version 2
Motivational nondirective resonance breathing (MNRB) version 2 will be delivered via a take-home guided breathing apparatus. Participants will be guided through a paced breathing session. Participants will practice MNRB version 2 for 15-minutes twice a day (once in the morning upon waking and once in the evening before bed) for 2 weeks.
Other: Motivational nondirective resonance breathing (MNRB)
Motivational nondirective resonance breathing (MNRB) is a type of diaphragmatic breathing technique that trains the body to breathe at resonance frequency with a mental state of open-awareness.
Other Names:
  • Diaphragmatic Breathing

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from Baseline Heart Rate Variability (HRV)
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
The root mean square of successive differences (RMSSD) will be derived from photoplethysmography (PPG) recordings and serve as the primary HRV outcome of interest. RMSSD corresponds to the parasympathetic regulation of heart beats (i.e. vagal activity) which is associated with self-report average pain intensity in CWP patients. Three readings on the right index finger are taken in a sitting position, separated by a one minute intervals, and after a five minute acclimatization (resting) period. The average of the last two measurements will be used in the final analyses.
Baseline (Pre-2 week Intervention); Post-2 week Intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from Baseline Numeric Rating Scale (NRS) for Average Pain Intensity
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
The NRS for pain is a unidimensional measure of pain intensity in adults. It is a segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of their pain where 0 represents ''no pain'' and 10 represents ''the worst pain imaginable''.
Baseline (Pre-2 week Intervention); Post-2 week Intervention
Change from Baseline Fibromyalgia severity (FS)
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
FS is a self-report measure of a participant´s overall CWP/fibromyalgia severity composed of their widespread pain index (WPI) and symptom severity scale (SSS). The WPI (0-19) is the number of areas in which the patient has had pain over the last week (0-19). The SSS (0-12) is the sum of the severity scores of 3 symptoms (fatigue, waking unrefreshed, and cognitive symptoms) (0-9) plus the sum (0-3) of the number of the following symptoms the patient has been bothered by that occurred during the previous 6 months: (1) Headaches (0-1) (2) Pain or cramps in lower abdomen (0-1) (3) And depression (0-1). The fibromyalgia severity (FS) scale is the sum of the WPI and SSS.
Baseline (Pre-2 week Intervention); Post-2 week Intervention
Change from Baseline Pain Detection Threshold (PDT), Pain Tolerance Threshold (PTT), and Pressure-Pain Limit (PPL)
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
Computerized cuff pressure algometry (CPA) will be used in order to safely and efficiently assess pain sensitivity mechanisms in CWP patients. The cuff will be placed on the mid-portion of the dominant lower leg and will use ramp inflation of 1 kPa/s until subjects indicate PDT, PTT, and PPL which is based upon an electronic 10cm visual analogue scale (VAS). PDT is the pressure value at the moment of transition between strong and painful pressure (the first time the VAS exceeds 0) whereas PTT is defined as the pressure value at the termination of pressure inflation (the corresponding VAS score is the PPL). The zero and 10 cm extremes on the VAS are defined accordingly as ''no pain'' and as ''the worst pain imaginable''.The subject is instructed to rate the pain intensity continuously on the VAS from the first sensation of pain and to press the hand-held pressure release button when the pain becomes unbearable. An average of three recordings will be used in the final analyses.
Baseline (Pre-2 week Intervention); Post-2 week Intervention
The Hopkins Symptom Checklist-25 (HSCL-25)
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
The HSCL-25 assesses emotional distress, anxiety, and depressive symptoms. The HSCL-25 scale consists of 25 questions about the presence and intensity of the most common psychiatric symptoms of anxiety and depression. Participants are asked: "To what extent have you been bothered by the following symptoms in the last 14 days including today?" Responses include: 1 (not at all), 2 (a little), 3 (quite a bit) and 4 (extremely).
Baseline (Pre-2 week Intervention); Post-2 week Intervention
Change from Baseline Blood Pressure (BP)
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
Resting systolic and diastolic BP will be measured using an automated oscillometric device. The correct size cuff is chosen after the circumference of the upper arm is measured. Following a two minute rest, three readings on the upper right arm are taken in a sitting position separated by one minute intervals. The average of the last two readings will be used in the final analyses.
Baseline (Pre-2 week Intervention); Post-2 week Intervention
EQ-5D-5L
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
The EQ-5D-5L is a standardized instrument to measure health-related quality of life. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of these dimensions has 5 levels: "no problems," "slight problems," "moderate problems," "severe problems" and "extreme problems". The digits for the five dimensions are then combined into a 5-digit number that describes the patient's health state. The EQ VAS uses a vertical visual analogue scale from 0 - 100 to record the patient's current state of health. The endpoints on the EQ VAS are labelled 'The best health you can imagine', indicated by 100, and 'The worst health you can imagine', indicated by 0.
Baseline (Pre-2 week Intervention); Post-2 week Intervention
Multidimensional Assessment of Interoceptive Awareness (MAIA)
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
The MAIA assesses participants' interoceptive body awareness and provides pertinent information in regards to how emotions and the perception of pain are related to interoception. The MAIA is a 32-item multidimensional instrument comprising of eight scales (e.g. noticing, non-distracting, not-worrying, attention regulation, emotional awareness, self-regulation, body listening, and trusting) ranging from 3 to 7 items each. Each of the 32-items are scored from a 0 to a 5 which indicates how often each statement applies in daily life (where 0 represents "never" and a 5 represents "always"). The average of all eight scales is then computed as a final score.
Baseline (Pre-2 week Intervention); Post-2 week Intervention
Spirituality and Coping (SpREUK-15)
Time Frame: Baseline (Pre-2 week Intervention); Post-2 week Intervention
The SpREUK-15 investigates whether or not participants rely on spirituality as a resource to cope with pain. It investigates three factors: 1) having trust/faith; 2) search for a transcendent source to rely on; and 3) reflection of life and subsequent change of life and behavior. Items are scored on a 5-point scale from disagreement to agreement (0 - does not apply at all; 1 - does not truly apply; 2 - don't know (neither yes nor no); 3 - applies quite a bit; 4 - applies very much). The scores can be referred to a 100% level (transformed scale score). Scores > 50% indicate higher agreement (positive attitude), while scores < 50 indicate disagreement (negative attitude).
Baseline (Pre-2 week Intervention); Post-2 week Intervention
Patient Global Impression of Change (PGIC)
Time Frame: Post-2 week Intervention
The PGIC is a self-report measure of participant belief about the efficacy of a treatment and their overall improvement. Participants rate their change on a 7 point scale: "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse".
Post-2 week Intervention
Credibility / Expectancy Questionnaire (CEQ)
Time Frame: Baseline (Pre-2 week Intervention)
The CEQ is a a self-report measure of a participant´s expectations about the efficacy of a particular treatment and whether they think that the treatment is credible or not. In particular, it investigates two factors-- what one feels and what one thinks in regards to the treatment. The CEQ is composed of six items which are scored on a 9 point scale ranging from: "not at all logical", "somewhat logical", and "very logical". Items 4 and 6 ask the participant how they feel and how they think the administered treatment will improve their overall health state in regards to their pain on a 0 - 100% scale, where 0% represents "no improvement" whereas 100% represents "total improvement".
Baseline (Pre-2 week Intervention)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Charles Ethan Paccione, M.S., M.A.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Audun Stubhaug, M.D., D.Med.Sci., Oslo University Hospital
  • Study Chair: Leiv Arne Rosseland, M.D.,Ph.D., Oslo University Hospital
  • Principal Investigator: Henrik B Jacobsen, Ph.D., Oslo University Hospital
  • Principal Investigator: Charles E Paccione, M.S., M.A., Oslo University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 15, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 9, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 9, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 6, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 8, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 4, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017/8892
  • 2017046 (Other Grant/Funding Number: South-East Regional Health Authority)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

All data will be de-identified. Data points will be reduced to ensure anonymity and will be uploaded to a server yet to be determined.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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