Neurofeedback for the Management of Neuropathic Pain in People With Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Pain intensity and affect
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 82 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Real EEG-neurofeedback
the NF intervention group will receive feedback based on the genuine real-time EEG activity
干预措施: EEG-neurofeedback (Behavioral)
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.
干预措施: EEG-neurofeedback (Behavioral)
结局指标
主要结局
Pain intensity and affect
时间窗: Before 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)
Pain intensity
时间窗: 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).
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.
次要结局
- Disability(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))
- Sleep quality(7 day diary before baseline and after intervention (approx. 8 weeks))
- z-score normalization(Before and after the intervention (approx. 8 weeks))
- Loreta z-score responders versus non-responders(Before and after the intervention (approx. 8 weeks))
- Neuropathic pain severity(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))
- 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.)
- Mood(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).)
- Pain catastrophizing(Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.)
- Quality of Life(Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.)
- Daily sleep interference(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).)
- Brief Pain Inventory (BPI) pain severity score(Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.)
- Fatigue(Inclusion visit (pre-intervention), post-treatment assessment (after the 10th and final neurofeedback session), and 4 months after completion of the intervention.)
研究者
Francois Pouwer
Professor
University of Southern Denmark