Neurofeedback for the Management of Neuropathic Pain in People With Diabetes

NCT06603792 | Recruiting DMC

• 1 other identifier: 11.719
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neuropathy, Painful Diabetic

Keywords

Neurofeedback; diabetic neuropathy; painful diabetic neuropathy; RCT; EEG-neurofeedback

Outcome Measures

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.

  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 (11)

• Neuropathic pain symptoms

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

• Pain interference

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

• Sleep

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

• Pain network abnormality burden

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

• Global impression of change

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

Study Arms (2)

Real EEG-neurofeedback

EXPERIMENTAL

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

Behavioral: EEG-neurofeedback

Sham EEG-neurofeedback

SHAM COMPARATOR

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

EEG-neurofeedback BEHAVIORAL

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.

Real EEG-neurofeedback; Sham EEG-neurofeedback

Eligibility Criteria

• Age: 18 Years - 82 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Southern Denmark: lead
• Region of Southern Denmark: collaborator
• European Foundation for the Study of Diabetes: collaborator
• Vissing fonden: collaborator
• Steno Diabetes Center Odense: collaborator
• Aarhus University Hospital: collaborator

Study Sites (1)

University of Southern Denmark

Odense, 5230, Denmark

RECRUITING

MeSH Terms

Conditions

Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Central Study Contacts

Francois Pouwer, Professor

CONTACT

+45 65 50 48 92; fpouwer@health.sdu.dk

Johanne Axelsen, PhD-student

CONTACT

jlaxelsen@health.sdu.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The project will investigate two randomized groups: a 'true' EEG-NF-group and 'sham' EEG-NF-group.

Study Record Dates

• First Submitted: August 29, 2024
• First Posted: September 19, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 15, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)