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RecruitingNCT06603792Updated Sep 15, 2026

Neurofeedback for the Management of Neuropathic Pain in People With Diabetes

An interventional study of EEG-neurofeedback in Neuropathy, Painful Diabetic, sponsored by University of Southern Denmark. Recruiting at 1 site in Denmark. Open to participants aged 18 Years to 82 Years. Per ClinicalTrials.gov, last updated 2026-09-15.

Sponsored by University of Southern Denmark · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Started Sep 2024; still recruiting 2 years 2 months later.
Phase
Not applicable
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
18 Years to 82 Years
Sex
All
01

Study summary

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.

Read the 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 blinded 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.

02

Conditions studied

  • Neuropathy, Painful Diabetic

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Keywords

  • Neurofeedback
  • diabetic neuropathy
  • painful diabetic neuropathy
  • RCT
  • EEG-neurofeedback
03

In context

Diabetic Neuropathies

538 studies on the registry are indexed under Diabetic Neuropathies; 80 are open to participants now.

This study's planned enrollment of 60 is below the median of 68 across 448 interventional studies indexed under Diabetic Neuropathies.

Browse Diabetic Neuropathies studies →

Lead sponsor

University of Southern Denmark is the lead sponsor of 336 studies on the registry; 46 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 82 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion criteria

  • Age ≥18 and ≤82 years
  • Diagnosed with 1) type 1 diabetes (for at least 5 years) or 2) type 2 diabetes
  • Confirmed diagnosis of at least "Probable Diabetic Polyneuropathy" as defined by Toronto Consensus Criteria (Presence of a combination of symptoms and signs of neuropathy including any two or more of the following: neuropathic symptoms, decreased distal sensation, or unequivocally decreased or absent ankle reflexes), and at least one of the following:

    • TCNS > 5
    • Abnormal DPNCheck results (amplitude \< 4µV and/or conduction velocity \< 40 m/s)
    • Abnormal NCS (Nerve Conduction Study)
  • Confirmed diagnosis of at least "Probable Neuropathic Pain" as defined by NeuPSIG guidelines (Pain distribution which makes neuropathic pain neuroanatomically plausible and history suggests relevant disease (e.g., symmetric pain in the feet/lower extremities and history of diabetes), and at least one of the following:

    • Negative or positive sensory signs, confined to innervation territory of the lesioned nervous structure (abnormal findings in at least one of: pinprick, temperature sensation, light touch (monofilament), vibration sense (biothesiometry or 128Hz tuning fork, position sense).
    • Abnormal DPNCheck results (amplitude \< 4µV and/or conduction velocity \< 40 m/s)
    • Abnormal NCS (Nerve Conduction Study)
  • 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
  • Concomitant neurological (neurodegenerative disorders, migraine, epilepsy, stroke, tumor) or 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).
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
60 participants (estimated)

Study arms

  • Experimental
    Real EEG-neurofeedback

    the NF intervention group will receive feedback based on the genuine real-time EEG activity

    Behavioral: EEG-neurofeedback

  • 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

Interventions

  • BehavioralEEG-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. NeuroGuide is used within the FDA 510(k)-cleared NeuroGuide Analysis System (K041263); clearance does not imply treatment validation.

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Seven consecutive days before baseline EEG assessment (T0; days -7 to -1) and seven consecutive days following the 10th and final neurofeedback session (T1; days +1 to +7).

Secondary outcomes

  1. 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.

    Time frame: Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.

  2. 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.

    Time frame: Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.

  3. Sleep

    Sleep disturbance will be assessed using the PROMIS sleep measure. Changes over time and between-group differences will be examined.

    Time frame: Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.

  4. 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.

    Time frame: Baseline EEG assessment and post-treatment EEG assessment after completion of the 10th and final neurofeedback session.

  5. Global impression of change

    Participants' overall perceived change in their condition will be assessed using the Patient Global Impression of Change (PGIC). Ratings following treatment and at follow-up will be summarized and compared between the real EEG-NF and sham EEG-NF groups as a supportive secondary outcome.

    Time frame: After completion of the 10th and final neurofeedback session (T1) and at 4-month follow-up (T2).

  6. Pain catastrophizing

    Pain catastrophizing and coping will be assessed using the Pain Catastrophizing Scale (PCS). 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.

    Time frame: Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.

  7. Quality of Life

    Quality of life will be assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF). 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.

    Time frame: Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.

  8. Daily sleep interference

    Sleep interference will be assessed using daily self-reported ratings collected as part of the electronic diary. Mean ratings will be derived for the predefined baseline and post-intervention assessment periods.

    Time frame: Seven consecutive days before baseline (T0; days -7 to -1) and seven consecutive days following the 10th and final neurofeedback session (T1; days +1 to +7).

  9. Brief Pain Inventory (BPI) pain severity score

    Pain severity will be assessed using the pain severity items of the Brief Pain Inventory (BPI). Changes over time and differences between the real EEG-NF and sham EEG-NF groups will be examined, with the 4-month follow-up used to assess durability of treatment effects.

    Time frame: Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.

  10. Mood

    Mood will be assessed using the PROMIS mood measure. Changes over time and between-group differences will be examined.

    Time frame: Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.

  11. Fatigue

    Fatigue will be assessed using the PROMIS fatigue measure. Changes over time and between-group differences will be examined.

    Time frame: Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 15, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06603792
Collaborators
European Foundation for the Study of Diabetes, Region of Southern Denmark, Vissing fonden, Steno Diabetes Center Odense, Aarhus University Hospital
Responsible party
Francois Pouwer (Professor, University of Southern Denmark) — Principal investigator
First posted
Sep 19, 2024
Start date
Sep 1, 2024
Primary completion
Feb 2027 (estimated)
Completion
Jun 2027 (estimated)
Last update
Sep 15, 2026

Study contacts

Francois Pouwer, Professor
Contact
fpouwer@health.sdu.dk
+45 65 50 48 92
Johanne Axelsen, PhD-student
Contact
jlaxelsen@health.sdu.dk

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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