Neurofeedback for the Management of Neuropathic Pain in People with Diabetes

September 16, 2024 updated by: Francois Pouwer, University of Southern Denmark
We will conduct a high-quality, blinded, randomized controlled trial (RCT) to rigorously test the effectiveness of EEG-based NF in patients with diabetes-related neuropathic pain in: 1) reducing pain intensity and pain affect, and 2) improving daily functioning and QoL.

Study Overview

Status

Status

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

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

20%-40% of people with diabetes develop diabetic polyneuropathy (DPN), which often manifests as a painful complication, strongly reducing quality of life. Current standard pharmacological treatments for neuropathic pain are often ineffective and have considerable side effects. Therefore, there is an urgent need for better treatment options. The way in which the brain interprets signals from the periphery can be modified through learning certain techniques, which can enable patients to modify signals related to painful DPN and consequently experience pain alleviation. Neurofeedback (NF) is a promising neuromodulatory therapy in which individuals receive real-time feedback about their brain's neurophysiological signals, thus increasing the volitional control of brain activity, reducing the experience of pain. Neurofeedback uses scalp EEG electrodes attached to a computer screen, which give real-time feedback to the individual. NF may offer symptom alleviation by teaching patients to regulate relevant activity patterns by themselves. By rewarding the person whenever the neural activity changes in a desired direction, the activity can be modulated. NF has not yet been investigated in an RCT in people with painful DPN. This proposed Danish-Brazilian project is the first triple blind RCT rigorously testing an EEG-NF intervention for neuropathic pain (NP) in diabetes. The treatment will be conducted over 10 sessions in two randomized groups: a real EEG-NF group and a sham (placebo) EEG-NF group. Brazilian participants will also undergo (functional) magnetic resonance imaging (fMRI) scanning to investigate how the NF-treatment targets and alters neural mechanisms. If found effective, the low-cost EEG-NF can be made available and implemented at large scale for people with diabetes and painful neuropathy, and will be in reach for low- to middle-income countries.

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 (Estimated)

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.
54

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.
  • Early Phase 1

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Denmark
      • Odense, Denmark, 5230
        • Recruiting
        • University of Southern Denmark
        • Contact:
        • Contact:
          • Francois Pouwer, Professor

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Age ≥18 and ≤82 years

  • Diagnosed with 1) type 1 diabetes (for at least 5 years) or 2) type 2 diabetes
  • The Toronto consensus criteria will be used for a case definition of DPN where patients have to have at least probable DPN (31). Diagnosis of DPN is confirmed with abnormal DPN Check. Painful DPN will be defined using the grading system for neuropathic pain (50) and will be in line with IASP's definition of neuropathic pain, i.e., "pain caused by a lesion or disease of the somatosensory system" (The Toronto consensus criteria).
  • TCNS score > 5
  • Eligible patients with painful DPN must have a pain intensity of at least 4 on an 11-point numerical rating scale (NRS, 0-10) for at least 3 months on at least semi-daily basis and no severe pain other than pain due to neuropathy (the pain intensity will be based on the pain the patients experience while on current pain treatment, if any).
  • Stable pain medication for > 1 month prior to inclusion. Exclusion criteria

Exclusion Criteria:

  • Concomitant neurological (neurodegenerative disorders, migraine, epilepsy, stroke, tumor) or clinically significant psychiatric illness
  • Neuropathy or neuropathic pain due to other causes than diabetes (vitamin B12 deficiency, prior treatment with neurotoxic chemotherapy, chronic alcohol abuse, spinal stenosis, etc.)
  • Change in current pain treatment during treatment (paracetamol is allowed as rescue medicine)
  • Prior or current excessive alcohol use (>14 or >21 units/week for women and men, respectively) or illegal substance abuse
  • Positive urine hCG test result indicating pregnancy
  • Morphine use >20mg/day
  • Blindness or severely impaired vision
  • The investigator finds the patient unfit for the study (e.g. due to use of alcohol or drugs, mental incapacity, unwillingness, or language barrier precluding adequate understanding or cooperation or presence of any condition that in the investigators' opinion may lead to poor adherence to study protocol).

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: Parallel Assignment
  • Masking: Double

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.
Experimental: Real EEG-neurofeedback
the NF intervention group will receive feedback based on the genuine real-time EEG activity
Behavioral: EEG-neurofeedback
Traditional neurofeedback uses one or two electrodes to modulate activity within a specific frequency band. Standardized Weighted Low Resolution Electromagnetic Tomography (swLORETA) analyzes the 3D distribution of intracortical brain electrical activity based on surface EEG recordings, enabling real-time brainwave imaging with a spatial resolution under one cubic centimeter. This divides the brain into over 12,000 voxels, offering localization similar to fMRI while maintaining EEG's faster temporal resolution. Source-localized NF can target specific, deeper brain regions, multiple Brodmann areas simultaneously, and provide feedback on connectivity between neural sources, enabling the training of specific neural networks. swLORETA metrics are compared to a normative database of neurotypical brains to produce z-scores for each area and metric. We will use the NeuroGuide normative database, FDA-approved and validated in peer-reviewed studies, widely used in clinical NF.
Sham Comparator: Sham EEG-neurofeedback
The sham-group will receive another participant's EEG-training protocol as a prerecorded signal. The feedback signal will consist of 15-25 rewards per minute. Meanwhile, the threshold for the sham group remains fixed, ensuring a consistent 70% positive feedback rate.
Behavioral: EEG-neurofeedback
Traditional neurofeedback uses one or two electrodes to modulate activity within a specific frequency band. Standardized Weighted Low Resolution Electromagnetic Tomography (swLORETA) analyzes the 3D distribution of intracortical brain electrical activity based on surface EEG recordings, enabling real-time brainwave imaging with a spatial resolution under one cubic centimeter. This divides the brain into over 12,000 voxels, offering localization similar to fMRI while maintaining EEG's faster temporal resolution. Source-localized NF can target specific, deeper brain regions, multiple Brodmann areas simultaneously, and provide feedback on connectivity between neural sources, enabling the training of specific neural networks. swLORETA metrics are compared to a normative database of neurotypical brains to produce z-scores for each area and metric. We will use the NeuroGuide normative database, FDA-approved and validated in peer-reviewed studies, widely used in clinical NF.

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
Pain intensity and affect
Time Frame: Before and after the intervention (approx. 8 weeks)
Change in self-reported pain intensity and pain affect (an average over a daily measurement in a 7-day pain diary using a numeric rating scale (NRS) from 0-10)
Before and after the intervention (approx. 8 weeks)

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
Neuropathic pain severity
Time Frame: Before and after the intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year from start until four months follow up)
Differences in neuropathic pain severity as measured by PROMIS. Both individually and between groups
Before and after the intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year from start until four months follow up)
Neuropathic pain severity
Time Frame: Before and after the intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year from start until four months follow up)
Differences in neuropathic pain severity as measured by the DN4. Both individually and between groups
Before and after the intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year from start until four months follow up)
Neuropathic pain severity
Time Frame: Before and after the intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year from start until four months follow up)
Differences in neuropathic pain severity as measured by the Neuropathic pain severity as measured by the Neuropathic Pain Scale (NPS). Both individually and between groups
Before and after the intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year from start until four months follow up)
Disability
Time Frame: Before and after intervention (approx. 8 weeks). Between groups after intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year after baseline)
Differences in disability as measured by the Brief Pain Inventory (BPI) (short form) and on the full BPI.
Before and after intervention (approx. 8 weeks). Between groups after intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year after baseline)
Sleep quality
Time Frame: 7 day diary before baseline and after intervention (approx. 8 weeks)
Daily sleep interference scale
7 day diary before baseline and after intervention (approx. 8 weeks)
z-score normalization
Time Frame: Before and after the intervention (approx. 8 weeks)
Normalization of the z-score of the targeted neural networks described in the training protocol for the NF-treatment.
Before and after the intervention (approx. 8 weeks)
Loreta z-score responders versus non-responders
Time Frame: Before and after the intervention (approx. 8 weeks)
Investigate Loreta z-score responders versus non-responders. Responders will be a subgroup of participants who showed any amount of decrease from baseline to last visit in the total number of significant z-scores within the targeted networks. Responders, whose z-scores move toward neurotypical levels (i.e., toward z = 0) will be compared to non-responders whose z-scores will not move in this expected direction.
Before and after the intervention (approx. 8 weeks)

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.
University of Southern Denmark

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Aarhus University Hospital
Region of Southern Denmark
European Foundation for the Study of Diabetes
Steno Diabetes Center Odense
Vissing fonden

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.
September 1, 2024

Primary Completion (Estimated)

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.
January 1, 2026

Study Completion (Estimated)

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.
June 1, 2026

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).
August 29, 2024

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.
September 16, 2024

First Posted (Estimated)

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.
September 19, 2024

Study Record Updates

Last Update Posted (Estimated)

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.
September 19, 2024

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.
September 16, 2024

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.
May 1, 2024

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.
  • 11.719

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

Yes

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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