Increasing Sensori-Motor Rhythm Activity by EEG-Neurofeedback to Reduce the Impact of Pain on Daily Functioning

Chronic Pain Syndrome Clinical Trial

— SMR-Pain  

Official title:

Relieving Peripheral Neuropathic Pain by Increasing the Power-ratio of Low-β Over High-β Activities in the Central Cortical Region With EEG-based Neurofeedback: Study Protocol for a Controlled Pilot Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06234917
• Other study ID #: 2020-A00514-35
• Status: Completed
• Phase: N/A
• Start date: January 4, 2021
• Est. completion date: February 1, 2023

Study information

• Verified date: January 2024
• Source: Institut pour la Pratique et l'Innovation en PSYchologie appliquée (Institut Pi-Psy)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background: Chronic neuropathic pain associated with peripheral neuropathies cannot be attributed solely to lesions of peripheral sensory axons and likely involves alteration in the processing of nociceptive information in the central nervous system in most patients. Few data are available regarding EEG correlates of chronic neuropathic pain. The fact is that effective cortical neuromodulation strategies to treat neuropathic pain target the precentral cortical region, i.e. a cortical area corresponding to the motor cortex. It is not known how these strategies might modulate brain rhythms in the central cortical region, but it can be speculated that sensorimotor rhythms (SMRs) are modified. Another potent way of modulating cortical rhythms is to use EEG-based neurofeedback (NFB). Rare studies previously aimed at relieving neuropathic pain using EEG-NFB training.

Methods/Design: The objective of this single-centre, single-blinded, randomized controlled pilot study is to assess the value of an EEG-NFB procedure to relieve chronic neuropathic pain in patients with painful peripheral neuropathy. A series of 32 patients will be randomly assigned to one of the two following EEG-NFB protocols, aimed at increasing either the low-β(SMR)/high-β ratio (n=16) or the α(μ)/θ ratio (n=16) at central (rolandic) cortical level. Various clinical outcome measures will be collected before and one week after 12 EEG-NFB sessions performed over 4 weeks. Resting-state EEG will also be recorded immediately before and after each NFB session. The primary endpoint will be the change in the impact of pain on patient's daily functioning, as assessed on the Interference Scale of the short form of the Brief Pain Inventory.

Discussion: The value of EEG-NFB procedures to relieve neuropathic pain has been rarely studied. This pilot study will attempt to show the value of endogenous modulation of brain rhythms in the central (rolandic) region in the frequency band corresponding to the frequency of stimulation currently used by therapeutic motor cortex stimulation. In the case of significant clinical benefit produced by the low-β(SMR)/high-β ratio increasing strategy, this work could pave the way for using EEG-NFB training within the armamentarium of neuropathic pain therapy.

Description:

1.1 - Description of the research proceedings and study design This is a single-centre, single-blinded, randomized controlled pilot study, in which 32 patients, aged between 18 and 80 years, suffering from painful peripheral neuropathy (DN4 and NRS pain scores ≥4/10), will be randomly assigned to one of the two following EEG-NFB protocols, aimed at increasing either the SMR/high-β ratio (n=16) or the μ/θ ratio (n=16) at central (rolandic) cortical level in a 1:1 allocation ratio, stratified by age and gender. The group allocation of the patients will be performed by one investigator not involved in the EEG-NFB task or clinical assessment. Patients will be recruited in the Clinical Neurophysiology department of the Henri Mondor University Hospital, Créteil, France, where the research will take place.

1.2 - Screening and inclusion visits During a routine medical visit, the study will be explained and proposed to the eligible patients and a letter of information about the protocol will be given to them. After a delay of reflection of at least a week, patients who agree to perform this research will be convened for an inclusion visit. After checking the inclusion/exclusion criteria, the informed consent form will be completed and signed by the participant and duly countersigned by the investigator.

During this visit, clinical assessment based on the fulfillment of different scales and questionnaires will be performed.

At the end of the inclusion visit, the patient will be randomized to either SMR/high-β or μ/θ training and the first EEG-NFB session will be performed.

1.3 - NFB trial The trial phase will consist of 12 EEG-NFB sessions over 4 weeks (on 3 consecutive days for 4 weeks). Each NFB session will last about 20 minutes, starting and ending with a recording of 2 minutes of resting-state EEG with eyes closed to investigate the impact of NFB on raw EEG. The NFB procedure will consist of 10 blocks of 75-second training separated by 15-second resting interval.

1.4 - Final visit and follow-up A visit will take place at the end of the trial, 7 days after the last NFB session. During this visit, subjects will be administered almost the same clinical evaluation that they received at the inclusion visit.

For the responders, defined as a reduction ≥30% of the 7-item Interference BPI score after the EEG-NFB procedure, an attempt to perform a transfer task will be proposed to the patient. From data collected during a semi-structured interview by the investigator on the strategy used by the patient to "succeed the game" during the NFB session, the mental process that the patient will have to use in the transfer task will be defined between the investigator and the patient. The purpose of the transfer task is to allow generalization of EEG-NFB benefit in real life conditions by realizing an NFB-like paradigm in which patients are invited to engage in the same cognitive strategies as for NFB but without presentation of the feedback signal.

The patient will have to perform the transfer task for 20 minutes every morning for three weeks. At the end of the third week, the investigator will make a phone call to the patient to record the 7-item Interference BPI score.

Study plan and measures:

Inclusion visit: Inclusion/exclusion criteria; Signed informed consent; DN4 questionnaire; Randomization; Baseline assessment (BFI-fr, FMI-fr, BIS-fr, CSI, Exp-LoC-Q); Primary clinical outcome measures: BPI; Other clinical outcome measures (NRS, VRS, NPSI, PCS, HAD, TMT, FSS, LSEQ) 10 EEG-NFB sessions (4 weeks): Resting-state EEG recording; EEG-NFB procedure

1 week after the last EEG-NFB session: Primary clinical outcome measures: BPI; Other clinical outcome measures (NRS, VRS, NPSI, PCS, HAD, TMT, FSS, LSEQ); Analgesic response, PGIC, Side effects After 3 weeks of transfer task (for responders to EEG-NFB): Primary clinical outcome measures: BPI

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 1, 2023
• Est. primary completion date: December 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Definite peripheral neuropathy on both clinical and neurophysiological grounds, present for at least 6 months.

• Neuropathic pain clearly related to the neuropathy, as defined by a score = 4/10 on the DN4 questionnaire.

• Score = 4/10 on a 0-10 numerical rating scale (NRS) concerning the average intensity of daily ongoing pain.

• Age between 18 and 80 years.

• Affiliation with the social security system.

• Ability to provide signed informed consent.

Exclusion Criteria:

• Neurological disorder other than peripheral neuropathy (neurodegenerative disorders, migraine, epilepsy, stroke, tumor).

• Psychiatric illness.

• Major visual disturbance.

Exclusion Criteria:

-

Related Conditions & MeSH terms

• Chronic Pain
• Chronic Pain Syndrome
• Neuralgia
• Peripheral Neuropathic Pain

Intervention

Other:
• EEG-based neurofeedback for brain activity modulation
NFB is a type of biofeedback technique for self-modulating brain activities by means of a learning task performed with ongoing sensory (usually visual) feedback to real-time acquisition of either brain imaging or electroencephalographic (EEG) signal, which serves as a biomarker of brain activity

Locations

Country	Name	City	State
France	Henri Mondor University Hospital	Creteil	Ile-de-France

Sponsors (1)

Lead Sponsor	Collaborator
Institut pour la Pratique et l'Innovation en PSYchologie appliquée (Institut Pi-Psy)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interference Scale of the short form of the Brief Pain Inventory (BPI)	The 7-item Interference Scale of the short form of the Brief Pain Inventory measures how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. It uses a 0 to 10 numeric rating scales for each item rating. The minimum score is 0 (no interference of pain on daily living activities, ie better outcome) and the maximum score is 70 (maximal interference of pain on daily living activities, ie worse outcome).	From enrollment to 7 days after the last NFB session
Secondary	Average intensity of daily ongoing pain on a 0-10 numeric rating scale (NRS)	The 0-10 numeric rating scale (NRS) measures the average intensity of daily ongoing pain. The minimum score is 0 (no pain, ie better outcome) and the maximum score is 10 (maximal pain, ie worse outcome).	From enrollment to 7 days after the last NFB session
Secondary	Average intensity of daily ongoing pain on a 0-5 verbal rating scale (VRS)	The 0-5 verbal rating scale (VRS) measures the average intensity of daily ongoing pain. The minimum score is 0 (no pain, ie better outcome) and the maximum score is 5 (unbearable pain, ie worse outcome).	From enrollment to 7 days after the last NFB session
Secondary	Symptomatic profile of neuropathic pain on the Neuropathic Pain Symptom Inventory (NPSI)	The Neuropathic Pain Symptom Inventory (NPSI) measures the neuropathic pain symptoms specifically. The minimum score is 0 (no pain, ie better outcome) and the maximum score is 100 (maximal neuropathic pain symptoms, ie worse outcome).	From enrollment to 7 days after the last NFB session
Secondary	Tendency to catastrophizing on the Pain Catastrophizing Scale (PCS)	The Pain Catastrophizing Scale (PCS) measures the tendency of catastrophizing in daily life. The minimum score is 0 (no catastrophism, ie better outcome) and the maximum score is 52 (maximal tendency to catastrophizing, ie worse outcome).	From enrollment to 7 days after the last NFB session
Secondary	Anxiety and depression on the Hospital Anxiety and Depression scale (HAD)	The Hospital Anxiety and Depression scale (HAD) measures the severity of anxiety and depression symptoms, with separate subscores for anxiety and depression. For each subscore, the minimum score is 0 (no anxiety or depression, ie better outcome) and the maximum score is 21 (maximal anxiety or depression, ie worse outcome).	From enrollment to 7 days after the last NFB session
Secondary	Fatigue on the Fatigue Severity Scale (FSS)	The Fatigue Severity Scale (FSS) measures the severity of fatigue. The minimum score is 0 (no fatigue, ie better outcome) and the maximum score is 63 (maximal fatigue, ie worse outcome).	From enrollment to 7 days after the last NFB session
Secondary	Quality of sleep on the Leeds Sleep Evaluation Questionnaire (LSEQ).	The Leeds Sleep Evaluation Questionnaire (LSEQ) measures the quality of sleep. The minimum score is 0 (poor sleep quality, ie worse outcome) and the maximum score is 100 (maximal sleep quality, ie better outcome).	From enrollment to 7 days after the last NFB session
Secondary	Dominant peak frequency (PF) of the EEG signal in each frequency band (?, µ, low-ß, and high-ß)	The dominant peak frequency (PF) of the EEG signal is measured in Hz for each frequency band (?, µ, low-ß, and high-ß). There is no better or worse outcome. This is a descriptive data.	At each NFB session through study completion, i.e. 4 weeks
Secondary	Absolute power (AP) of the EEG signal in each frequency band (?, µ, low-ß, and high-ß)	The absolute power (AP) of the EEG signal is measured in µV² for each frequency band (?, µ, low-ß, and high-ß). There is no better or worse outcome. This is a descriptive data.	At each NFB session through study completion, i.e. 4 weeks
Secondary	Relative power (RP) of the EEG signal in each frequency band (?, µ, low-ß, and high-ß)	The relative power (RP) of the EEG signal is measured in % for each frequency band (?, µ, low-ß, and high-ß). There is no better or worse outcome. This is a descriptive data.	At each NFB session through study completion, i.e. 4 weeks