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Body Versus Machine: Deep Breathing Versus Vagus Stimulation for the Treatment of Chronic Widespread Pain

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ClinicalTrials.gov Identifier: NCT03180554
Recruitment Status : Not yet recruiting
First Posted : June 8, 2017
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
Charles Ethan Paccione, M.S., M.A., Oslo University Hospital

Tracking Information
First Submitted Date  ICMJE June 6, 2017
First Posted Date  ICMJE June 8, 2017
Last Update Posted Date March 6, 2019
Estimated Study Start Date  ICMJE March 2019
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
  • 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.
  • 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''.
Original Primary Outcome Measures  ICMJE
 (submitted: June 7, 2017)
  • Change from Baseline Heart Rate Variability (HRV) at 6 weeks [ Time Frame: Baseline (Pre-6 week Intervention); Post-6 week Intervention ]
    The root mean square of successive differences (RMSSD) will be derived from electrocardiogram (ECG) recordings and serve as the primary outcome. RMSSD corresponds to the parasympathetic regulation of heart beats which is associated with pain intensity.
  • Change from Baseline Numeric Rating Scale (NRS) for Pain at 6 weeks [ Time Frame: Baseline (Pre-6 week Intervention); Post-6 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. This will provide a subjective evaluation of pain intensity as compared to the parasympathetic tone of each patient.
Change History Complete list of historical versions of study NCT03180554 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
  • 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.
  • 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.
  • 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".
  • 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".
  • 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.
  • 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).
  • 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.
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2017)
Change from Baseline Conditioned Pain Modulation (CPM) at 6 weeks [ Time Frame: Baseline (Pre-6 week Intervention); Post-6 week Intervention ]
Conditioned pain modulation (CPM) will test endogenous pain inhibition and pro-nociceptive patterns of pain modulation. Heat pain ratings are taken from one arm while the other arm is immersed in a hot water bath. CPM will be tested using the published protocol from the Tromsø Study, in Tromsø, Norway. This gives us comparison data from over 10000 people, increasing the ecological value of the CPM measure.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: June 7, 2017)
  • Change from Baseline Cortisol at 6 weeks [ Time Frame: Baseline (Pre-6 week Intervention); Post-6 week Intervention ]
    Hair Cortisol analysis presents a means of monitoring chronic stress, capturing systemic cortisol exposure over longer periods of time. Hair samples can be easily attained while cortisol can be measured by using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised.
  • Change from Baseline Pro-Inflammatory and Anti-Inflammatory Cytokines at 6 weeks [ Time Frame: Baseline (Pre-6 week Intervention); Post-6 week Intervention ]
    Venus blood samples will be taken from the median cubital vein in order to evaluate and analyse pro-inflammatory cytokine concentrations (i.e. interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 8 (IL-8)) and anti-inflammatory cytokines (i.e. interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10)).
 
Descriptive Information
Brief Title  ICMJE Body Versus Machine: Deep Breathing Versus Vagus Stimulation for the Treatment of Chronic Widespread Pain
Official Title  ICMJE Body Versus Machine: Motivational Nondirective Resonance Breathing Versus Transcutaneous Vagus Nerve Stimulation for the Treatment of Chronic Widespread Pain
Brief Summary 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.
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. Primary outcomes are photoplethysmography (PPG) measured heart rate variability (HRV) and self report numeric rating scale (NRS) pain intensity. Secondary outcomes are pain detection threshold (PDT) and pain tolerance threshold (PTT) determined by pressure cuff algometry, blood pressure, as well as health related quality of life.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:
This study will use a randomized controlled experimental design. A total of N=112 consenting CWP patients will be consecutively recruited from the Department of Pain Management and Research at Oslo University Hospital, Norway, and randomized to one of four intervention groups. Participants will be randomized to either a version 1 tVNS group, a version 2 tVNS group, a version 1 MNRB group, or a version 2 MNRB group. Both version 1 and 2 treatment interventions will be delivered at home, twice a day, for 15 min in the morning and for 15 min in the evening, for a total duration of 2 weeks. The participants' adherence to both interventions will be monitored electronically. An 80 % completion of tVNS stimulation and MNRB training will be regarded as adequate adherence in this project. Participants are invited to the clinic twice for pre- and post-intervention data collection.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description:
All statistical analyses will be performed by a statistician who is blinded by participants' ID and health record.
Primary Purpose: Treatment
Condition  ICMJE Chronic Widespread Pain
Intervention  ICMJE
  • 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 Name: Vagus Nerve Stimulation
  • 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 Name: Diaphragmatic Breathing
Study Arms  ICMJE
  • 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.
    Intervention: Device: Transcutaneous Vagal Nerve Stimulation (tVNS)
  • 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.
    Intervention: Device: Transcutaneous Vagal Nerve Stimulation (tVNS)
  • 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.
    Intervention: Other: Motivational nondirective resonance breathing (MNRB)
  • 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.
    Intervention: Other: Motivational nondirective resonance breathing (MNRB)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 19, 2019)
112
Original Estimated Enrollment  ICMJE
 (submitted: June 7, 2017)
100
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Charles E Paccione, M.S., M.A. 23026161 ext +47 chapac@ous-hf.no
Contact: Henrik B Jacobsen, Psy.D., Ph.D. heboja@ous-hf.no
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03180554
Other Study ID Numbers  ICMJE 2017/8892
2017046 ( Other Grant/Funding Number: South-East Regional Health Authority )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
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.
Responsible Party Charles Ethan Paccione, M.S., M.A., Oslo University Hospital
Study Sponsor  ICMJE Charles Ethan Paccione, M.S., M.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Audun Stubhaug, M.D., Ph.D. Oslo University Hospital
Study Chair: Leiv Arne Rosseland, M.D.,Ph.D. Oslo University Hospital
PRS Account Oslo University Hospital
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP