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. This study aims to determine the short-term and long-term effects of EEG-based NF on self-reported pain intensity, neuropathic pain symptoms, daily functioning, QoL and neurophysiological activity in individuals with chronic P-DPN. The trial is designed as a superiority trial. The primary aim is to evaluate whether real EEG-NF compared with sham EEG-NF, leads to a greater reduction in self-reported pain intensity from T0 to T1, assessed using mean 7-day pain intensity derived from the electronic pain diary. Secondary aims are to examine whether EEG-NF improves neuropathic pain severity, pain interference, sleep, fatigue, mood and QoL, and promotes normalization of activity within predefined pain-related cortical networks assessed using z-score changes in standardized weighted low-resolution electromagnetic tomography (swLORETA)-derived regions.
Age ≥18 and ≤82 years
Diagnosed with 1) type 1 diabetes (for at least 5 years) or 2) type 2 diabetes
TCNS > 5
Abnormal DPNCheck results (amplitude < 4µV and/or conduction velocity < 40 m/s)
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
Parallel
EEG-neurofeedback
BehavioralTraditional 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. NeuroGuide is used within the FDA 510(k)-cleared NeuroGuide Analysis System (K041263); clearance does not imply treatment validation.
Pain intensity
The primary aim is to evaluate whether real EEG-NF compared with sham EEG-NF, leads to a greater reduction in self-reported pain intensity (NRS from 0-10) from T0 (baseline) to T1 (after 10th and final session), assessed using mean 7-day pain intensity derived from an electronic pain diary.
Neuropathic pain symptoms
Differences in neuropathic pain symptoms will be assessed using the Neuropathic pain scale (NPS). Changes from baseline will be evaluated following the intervention and at 4-month follow-up, and differences between the real EEG-NF and sham EEG-NF groups will be examined.
Pain interference
Pain interference will be assessed using the Brief Pain Inventory (BPI) interference scale. Changes from baseline will be evaluated following the intervention and at 4-month follow-up, and differences between the real EEG-NF and sham EEG-NF groups will be examined.
Sleep
Sleep disturbance will be assessed using the PROMIS sleep measure. Changes over time and between-group differences will be examined.
Pain network abnormality burden
Neurophysiological outcomes will be assessed using normative z-scores within the predefined pain-related network. A composite pain-network abnormality burden will be derived across EEG features, with domain-specific measures for current source density (CSD), instantaneous coherence, and lagged coherence also examined. Changes from pre- to post-intervention will be compared between the real EEG-NF and sham EEG-NF groups.
Click on the lead sponsor to view all of their trials.
University of Southern Denmark
Lead sponsor
European Foundation for the Study of Diabetes
Collaborator
Region of Southern Denmark
Collaborator
Vissing fonden
Collaborator
Steno Diabetes Center Odense
Collaborator
Aarhus University Hospital
Collaborator
