Peripheral NeuropathyNCT04242797
Central Mechanisms of Calmare: an fMRI Trial
A study testing Calmare and TENS in people with Peripheral Neuropathy, run by Brigham Young University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Peripheral Neuropathy
- What is being tested?
- Calmare and TENS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2015to 15 Nov 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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."
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Peripheral Neuropathy
- Being tested
- Calmare, TENS
- Keywords
- Idiopathic, diabetic, chemotherapy-induced
- Medical subject headings
- Peripheral Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CalmareDevice
Skin is stimulated with an electrical voltage via electrode pads, variably distorted sine wave at ~47 Hz.
TENSDevice
Also called Traditional TENS
Skin is stimulated with an electrical voltage via electrode pads, 300 micro-second rectangle pulse at 47 Hz.
| Study group | Role | What they receive |
|---|---|---|
| Calmare | Active comparator | Single- or ten-dose treatments on consecutive weekdays, 30 minutes each. Receives: Device: Calmare |
| Traditional TENS | Active comparator | Single- or ten-dose treatments on consecutive weekdays, 30 minutes each. Receives: Device: TENS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analaog Scale (VAS) Pain Score Changes
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).
Measured: 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)
Washington Neuropathic Pain Scale (WNPS) Pain Score Changes
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).
Measured: 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)
Changes in resting fMRI Correlations
Change in temporal correlations of resting fMRI signals from 93 cerebral regions of interest.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2020
- Study start1 Aug 2015
- Primary completion15 Nov 2017
- Study completion15 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral NeuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham Young University
- Sponsor type
- University, hospital or other
- Collaborators
- Sorenson Legacy Foundation, Brigham Young University MRI Research Facility
- Responsible party
- Principal investigator, David D Busath, Brigham Young University
- Investigators
- David D Busath, M.D., Principal investigator, Brigham Young University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04242797
- Sponsor's protocol ID
- F15130
- Status last verified
- Jan 2020
- First submitted
- 21 Jan 2020
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Majithia N, Smith TJ, Coyne PJ, Abdi S, Pachman DR, Lachance D, Shelerud R, Cheville A, Basford JR, Farley D, O'Neill C, Ruddy KJ, Sparadeo F, Beutler A, Loprinzi CL. Scrambler Therapy for the management of chronic pain. Support Care Cancer. 2016 Jun;24(6):2807-14. doi: 10.1007/s00520-016-3177-3. Epub 2016 Apr 4.
PubMed 27041741
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Central Mechanisms of Calmare: an fMRI Trial
- ClinicalTrials.gov ID
- NCT04242797
- Acronym / sponsor ID
- F15130
- Conditions
- Peripheral Neuropathy
- Keywords
- Idiopathic, diabetic, chemotherapy-induced
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Brigham Young UniversityUniversity, hospital or other
- Collaborators
- Sorenson Legacy Foundation, Brigham Young University MRI Research Facility
- Study start
- 1 Aug 2015 (actual)
- Primary completion
- 15 Nov 2017 (actual)
- Study completion
- 15 Nov 2017 (actual)
- First posted
- 27 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Calmare | Active comparator | Device: CalmareSingle- or ten-dose treatments on consecutive weekdays, 30 minutes each. |
| Traditional TENS | Active comparator | Device: TENSSingle- or ten-dose treatments on consecutive weekdays, 30 minutes each. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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."
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CalmareSkin is stimulated with an electrical voltage via electrode pads, variably distorted sine wave at ~47 Hz. | Device | Calmare |
| TENSAlso: Traditional TENSSkin is stimulated with an electrical voltage via electrode pads, 300 micro-second rectangle pulse at 47 Hz. | Device | Traditional TENS |
Primary outcome
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).
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).
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Background: PubMed 27041741Majithia N, Smith TJ, Coyne PJ, Abdi S, Pachman DR, Lachance D, Shelerud R, Cheville A, Basford JR, Farley D, O'Neill C, Ruddy KJ, Sparadeo F, Beutler A, Loprinzi CL. Scrambler Therapy for the management of chronic pain. Support Care Cancer. 2016 Jun;24(6):2807-14. doi: 10.1007/s00520-016-3177-3. Epub 2016 Apr 4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David D Busath, M.D. principal investigator
Brigham Young University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Calmare and TENS in people with Peripheral Neuropathy, run by Brigham Young University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04242797, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.