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Neurofeedback for the Management of Neuropathic Pain in People with Diabetes

Early Phase 1
Recruiting
Conditions
Neuropathy, Painful Diabetic
Interventions
Behavioral: EEG-neurofeedback
Registration Number
NCT06603792
Lead Sponsor
University of Southern Denmark
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
54
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Real EEG-neurofeedbackEEG-neurofeedbackthe NF intervention group will receive feedback based on the genuine real-time EEG activity
Sham EEG-neurofeedbackEEG-neurofeedbackThe 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.
Primary Outcome Measures
NameTimeMethod
Pain intensity and affectBefore and after the intervention (approx. 8 weeks)

Change in self-reported pain intensity and pain affect (an average over a daily measurement in a 7-day pain diary using a numeric rating scale (NRS) from 0-10)

Secondary Outcome Measures
NameTimeMethod
Neuropathic pain severityBefore and after the intervention (approx. 8 weeks) and at 4 months follow-up (approx. a half year from start until four months follow up)

Differences in neuropathic pain severity as measured by the Neuropathic pain severity as measured by the Neuropathic Pain Scale (NPS). Both individually and between groups

DisabilityBefore 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)

Differences in disability as measured by the Brief Pain Inventory (BPI) (short form) and on the full BPI.

Sleep quality7 day diary before baseline and after intervention (approx. 8 weeks)

Daily sleep interference scale

z-score normalizationBefore and after the intervention (approx. 8 weeks)

Normalization of the z-score of the targeted neural networks described in the training protocol for the NF-treatment.

Loreta z-score responders versus non-respondersBefore and after the intervention (approx. 8 weeks)

Investigate Loreta z-score responders versus non-responders. Responders will be a subgroup of participants who showed any amount of decrease from baseline to last visit in the total number of significant z-scores within the targeted networks. Responders, whose z-scores move toward neurotypical levels (i.e., toward z = 0) will be compared to non-responders whose z-scores will not move in this expected direction.

Trial Locations

Locations (1)

University of Southern Denmark

🇩🇰

Odense, Denmark

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