Clinical trial NCT06603792: Neurofeedback for the Management of Neuropathic Pain in People with Diabetes
Official title: Neurofeedback for the Management of Neuropathic Pain in People with Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Neuropathy, Painful Diabetic
Keywords: Neurofeedback
diabetic neuropathy
painful diabetic neuropathy
RCT
EEG-neurofeedback
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: European Foundation for the Study of Diabetes
name: Region of Southern Denmark
name: Vissing fonden
name: Steno Diabetes Center Odense
name: Aarhus University Hospital
First posted: 2024-09-19
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 82
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The project will investigate two randomized groups: a 'true' EEG-NF-group and 'sham' EEG-NF-group.
Primary purpose: TREATMENT

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.

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).
* Stable pain medication for \> 1 month prior to inclusion. Exclusion criteria

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).

Primary outcomes:
measure: Pain intensity and affect
timeFrame: Before and after the intervention (approx. 8 weeks)
Secondary outcomes:
measure: Neuropathic pain severity
timeFrame: 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)
measure: Neuropathic pain severity
timeFrame: 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)
measure: Neuropathic pain severity
timeFrame: 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)
measure: Disability
timeFrame: 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)
measure: Sleep quality
timeFrame: 7 day diary before baseline and after intervention (approx. 8 weeks)
measure: z-score normalization
timeFrame: Before and after the intervention (approx. 8 weeks)
measure: Loreta z-score responders versus non-responders
timeFrame: Before and after the intervention (approx. 8 weeks)
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: University of Southern Denmark
Study officials:
References: