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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
54
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.
University of Southern Denmark
Odense, Denmark
RECRUITINGPain intensity and affect
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)
Time frame: Before and after the intervention (approx. 8 weeks)
Neuropathic pain severity
Differences in neuropathic pain severity as measured by PROMIS. Both individually and between groups
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)
Neuropathic pain severity
Differences in neuropathic pain severity as measured by the DN4. Both individually and between groups
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)
Neuropathic pain severity
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
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)
Disability
Differences in disability as measured by the Brief Pain Inventory (BPI) (short form) and on the full BPI.
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)
Sleep quality
Daily sleep interference scale
Time frame: 7 day diary before baseline and after intervention (approx. 8 weeks)
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z-score normalization
Normalization of the z-score of the targeted neural networks described in the training protocol for the NF-treatment.
Time frame: Before and after the intervention (approx. 8 weeks)
Loreta z-score responders versus non-responders
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.
Time frame: Before and after the intervention (approx. 8 weeks)