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Central Mechanisms of Calmare: an fMRI Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04242797
Recruitment Status : Completed
First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Sorenson Legacy Foundation
Brigham Young University MRI Research Facility
Information provided by (Responsible Party):
David D Busath, Brigham Young University

Brief Summary:
Pilot one-treatment and extended 10-treatment studies are carried out on participants with peripheral neuropathy comparing traditional TENS and Calmare stimulation protocols using a double-blind apparatus. Resting fMRI scans are obtained before and after the treatment, as well as after most of the pain has returned.

Condition or disease Intervention/treatment Phase
Peripheral Neuropathy Device: Calmare Device: TENS Not Applicable

Detailed Description:

Pain can be either useful or harmful. Acute pain conveys information to the brain about real or potential damage that can productively lead to avoidance or treatment of the damage. However, chronic pain, which extends beyond these useful purposes, becomes a potentially debilitating inconvenience. Estimations based on surveys report that as many as 33% of Americans suffer from chronic pain, with a significant portion being unable to successfully manage it.

The current means to treating chronic pain include: surgery, drug therapy, physical therapy, psychological intervention, and others. Unfortunately, despite these options, many people continue to suffer from a chronic pain condition. Neuropathic pain, or pain caused by nervous system damage, is particularly hard to treat. Drug therapy and surgery have relatively low success rates and undesirable side effects. Thus, there is a need for additional research and new treatment methods for neuropathic pain patients.

The Calmare device was designed as one such means to treat chronic neuropathic pain. It works through electrostimulation of the skin near the pain site, and, according to recent studies, has significantly reduced chronic neuropathic pain in most subjects (Majithia et al., 2016).

Previous studies of Calmare effectiveness have defined the success of treatment as the reduction of reported pain levels by the patient. Though useful, these studies fail to provide an objective measurement of pain reduction and fail to discover the mechanisms by which it occurs. In addition, previous studies have been unable to perform a true double-blind experiment in which the placebo effect was entirely accounted for. The pilot study takes a step toward filling this gap by performing a double blind, randomized single-treatment trial comparing Calmare efficacy to traditional transcutaneous electrical nerve stimulation (TENS) efficacy. The ten-treatment study examines the durability of the pain relief for 12 weeks after the treatment period.

The goal of these studies is two-fold: first, to use fMRI before and after a full therapeutic Calmare treatment course to determine the extent to which Calmare affects the connectivity of the pain centers of the brain, and second, to determine whether traditional TENS or Calmare is more effective in reducing neuropathic chronic pain. The Calmare treatment is administered in a double-blind fashion with neither the technician, nor the subject knowing whether the TENS or the Calmare is being administered. The investigator's hypothesis is that Calmare therapy decreases subject pain through a central mechanism that will be manifest in decreased functional connectivity of the brain's pain centers. The degree to which this happens is determined by comparing the decrease in pain intensity, as reported by the patient, with the difference in fMRI BOLD temporal correlations between pain centers.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Equal numbers of participants are randomly assigned to either the Calmare or traditional TENS group. Using skin electrodes positioned by the therapist proximal to the limb pain, each participant is given the assigned stimulation mode for 30-minute therapy sessions. One therapy is used in the pilot study and ten therapies on consecutive weekdays in the extended study.
Masking: Double (Participant, Care Provider)
Masking Description: The investigator uses Bluetooth to control the output of a switching box for each patient from outside the treatment room. The box controls whether the inputs from the Calamare device or two traditional dual-channel TENS devices are connected to the output. The stimulus amplitude knobs for the TENS units are ganged to those of the Calmare using O-rings. When the therapist increases the stimulus amplitude on Calmare, that of the corresponding TENS unit is increased to about the same extent simultaneously.
Primary Purpose: Treatment
Official Title: Central Mechanisms of Calmare: an fMRI Trial
Actual Study Start Date : August 1, 2015
Actual Primary Completion Date : November 15, 2017
Actual Study Completion Date : November 15, 2017

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Calmare
Single- or ten-dose treatments on consecutive weekdays, 30 minutes each.
Device: Calmare
Skin is stimulated with an electrical voltage via electrode pads, variably distorted sine wave at ~47 Hz.

Active Comparator: Traditional TENS
Single- or ten-dose treatments on consecutive weekdays, 30 minutes each.
Device: TENS
Skin is stimulated with an electrical voltage via electrode pads, 300 micro-second rectangle pulse at 47 Hz.
Other Name: Traditional TENS

Primary Outcome Measures :
  1. Visual Analaog Scale (VAS) Pain Score Changes [ Time Frame: The intra-subject change in VAS score from pre-Rx baseline a) after the 30-minute treatment and b) again the next day (pilot), or a) after each of the ten 30-minute treatments and b) 6- and 12-weeks from end of treatment (extended) ]
    Change from baseline in VAS score, which is marked on a line labeled 0 on the left (no pain) and 10 on the right (the most exquisite pain imaginable).

  2. Washington Neuropathic Pain Scale (WNPS) Pain Score Changes [ Time Frame: The intra-subject change in ten WNPS pain scores from baseline after the 30-minute Rx and again the next day (pilot) or after each of the ten 30-minute Rxs and 6- and 12-weeks from end of Rx period (extended) ]
    Change from baseline in each of ten WNPS scores, which are marked boxes have integral values of 0 on the left (no pain) and 10 on the right (the most exquisite pain imaginable).

  3. Changes in resting fMRI Correlations [ Time Frame: Intra-subject changes in fMRI signals from baseline (taken immediately before first Rx) obtained 30 minutes after first Rx (pilot) or 10th Rx (extended) and again 24 hours later (pilot) or 6-weeks later (extended). ]
    Change in temporal correlations of resting fMRI signals from 93 cerebral regions of interest.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • They must have suffered from a diagnosed peripheral neuropathy (diabetic, chemotherapy induced, or other) for a minimum of 6 months.
  • At the time of the study they must experience pain greater than or equal to 5 on a visual analog pain scale from 0-10, with 0 being "no pain" and 10 being "the worst imaginable pain."

Exclusion Criteria:

  • pregnancy
  • a history of epilepsy or brain damage
  • presence of a serious psychiatric disorder (e.g. schizophrenia, manic-depressive psychosis, primary major depression)
  • multiple sources of chronic pain (e.g. a chronic pain condition other than a peripheral neuropathy or more than one site of neuropathies)
  • a skin condition that would prevent application of skin electrodes
  • latex allergy
  • severe arrhythmia or any form of equivalent heart disease
  • history of myocardial infarction or ischemic heart disease within the past 6 months
  • celiac plexus block or other neurolytic pain control treatment within the past 4 weeks
  • state of active withdrawal from drugs and/or alcohol
  • ineligible for fMRI due to metal implants, etc.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04242797

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United States, Utah
BYU MRI Research Facility
Provo, Utah, United States, 84602-1018
Sponsors and Collaborators
Brigham Young University
Sorenson Legacy Foundation
Brigham Young University MRI Research Facility
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Principal Investigator: David D Busath, M.D. Brigham Young University
  Study Documents (Full-Text)

Documents provided by David D Busath, Brigham Young University:
Informed Consent Form  [PDF] June 22, 2016

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Responsible Party: David D Busath, Professor, Brigham Young University Identifier: NCT04242797    
Other Study ID Numbers: F15130
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by David D Busath, Brigham Young University:
Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases