Neurofeedback for the Management of Neuropathic Pain in People with Diabetes

NCT ID: NCT06603792

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-01
• Study Completion Date: 2026-06-30

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 in: 1) reducing pain intensity and pain affect, and 2) improving daily functioning and QoL.

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.

Conditions

Neuropathy, Painful Diabetic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Real EEG-neurofeedback

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

Group Type: EXPERIMENTAL

EEG-neurofeedback

Intervention Type: 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. We will use the NeuroGuide normative database, FDA-approved and validated in peer-reviewed studies, widely used in clinical NF.

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.

Group Type: SHAM_COMPARATOR

EEG-neurofeedback

Intervention Type: 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. We will use the NeuroGuide normative database, FDA-approved and validated in peer-reviewed studies, widely used in clinical NF.

Interventions

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.

Intervention Type: BEHAVIORAL

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
• 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).

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 82 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Foundation for the Study of Diabetes

OTHER

Sponsor Role: collaborator

Region of Southern Denmark

OTHER

Sponsor Role: collaborator

Vissing fonden

UNKNOWN

Sponsor Role: collaborator

Steno Diabetes Center Odense

OTHER

Sponsor Role: collaborator

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

University of Southern Denmark

OTHER

Sponsor Role: lead

Responsible Party

Francois Pouwer

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Southern Denmark

Odense, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Francois Pouwer, Professor

Role: CONTACT

fpouwer@health.sdu.dk

+45 65 50 48 92

Johanne Axelsen, PhD-student

Role: CONTACT

jlaxelsen@health.sdu.dk

Facility Contacts

Johanne Axelsen, PhD-student

Role: primary

jlaxelsen@health.sdu.dk

+45 65 50 48 94

Francois Pouwer, Professor

Role: backup

Other Identifiers

11.719

Identifier Type: -

Identifier Source: org_study_id