Brain Activity Patterns in Persons With Spinal Cord Injury and Neuropathic Pain After a Virtual Walking Training Program

Spinal Cord Injuries Clinical Trial

— VRandMRI  

Official title:

Are Changes in Pain Perception Associated With Changes in Brain Activity Patterns in Persons With Spinal Cord Injury and Neuropathic Pain After a Virtual Walking Training Program - A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05098587
• Other study ID #: 2020-13
• Status: Completed
• Start date: August 30, 2021
• Est. completion date: January 10, 2023

Study information

• Verified date: March 2024
• Source: Swiss Paraplegic Research, Nottwil
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this pilot study is to explore the association of changes in pain perception with changes in brain activity (functional Magnetic Resonance Imaging (fMRI)) and metabolic (Magnetic Resonance Spectroscopy (MRS)) patterns of individuals with SCI and chronic NeP after a Virtual Walk (VW) therapy. The brain activity patterns will be assessed in resting state and under a specific task, before and after a VW training program, done as part of the clinical routine, as well as at a four weeks follow-up.

The results of this pilot study will serve as basis for a bigger project that aims to investigate and compare brain activity and long-term effects of non-immersive VW therapy on chronic NeP in individuals with SCI (traumatic SCI with chronic NeP at- or below level, complete or incomplete) taking into account confounding factors such as time since injury, level of injury and type of NeP.

Description:

This pilot study consists of specific assessments at four different time points (T0=screening, T1=baseline, pre measurement, T2=post measurement, T3=four week follow-up).

The physiotherapeutical assessment at T0 involves the evaluation of the imagery capacity. At T1, the participant will be assessed for baseline measures before starting with the VW training. At T2 (after the last VW training) and at T3 (four weeks after the last VW training), the participant will be assessed for outcome measures.

Sociodemographic and clinical characteristics (age, sex, education level, workability, age at injury, lesion level, comorbidities, complications, concomitant injuries, SCI pain basic dataset 2.0 and medication) will be collected in the screening/recruitment phase but only used after receiving informed consent from each participant.

Participants will undergo a non-invasively MRI examination without application of contrast agents. The functional activity of the brain will be assessed by a blood oxygenation level-dependent (BOLD) fMRI. The metabolic profile will be assessed non-invasively by means of single voxel MRS. Prior to the fMRI and MRS measurements, a high-resolution anatomical MRI will be performed, which serves for tissue segmentation and planning purposes.

The MRI will consist out of the following sequences conducted in an MRI scanner (six minutes duration each):

1. MRS sequence: The metabolic profile will be assessed with single voxel spectroscopy in the Anterior Cingulate Cortex and the Thalamus.

2. Resting-state fMRI: The participant will stay rested with open eyes and does not have to perform a specific task.

3. Task-based fMRI: In an on-off scheme, a sequence of neutral (not pain related) pictures on a screen, mounted outside of the MRI machine will be shown. The pictures will change every 20 seconds in a random order to keep the participant alert.

4. Task-based fMRI: In an on-off scheme, a sequence of pain-related pictures on a screen, mounted outside of the MRI machine will be shown. The pictures will change every 20 seconds in a random order to keep the participant alert.

5. Resting-state fMRI: The participant will stay rested with open eyes and does not have to execute a task.

The pain images shown during the task-based fMRI are a validated set of pictures.

The participants will receive a pain diary. This pain diary is filled in daily for the one-week period before the baseline assessments, during the VW therapy and in the week before the last assessments at T3. To minimise the risk of missing data in the pain diary the participants will be called one week before T3 and get reminded to fill in the pain diary.

Before starting with the VW therapy the participants will first perform a subitem of the standardised Graded Motor Imagery (GMI) training over four weeks, five times a day using the Recognise Foot App and the Recognise Hand App. The participants will train their capacity to perform a left-right discrimination for hands and feet. This training will help to improve the therapeutic effect of the following VW therapy program, by improving the imagery capacity. Reaction time as well as accuracy while performing a left-right discrimination task will be measured. More than 80% correct answers and a reaction time of less than two seconds is interpreted as good imagery capacity. The imagery capacity will be assessed right before the start of the discrimination training, after two weeks and after four weeks. This serves on one hand as information about participant characteristics and on the other hand as a control mechanism that each participant keeps performing this training.

After the discrimination training, the participants will perform a non-immersive VW therapy program at the pain clinic, which consists of five sessions of 10 to 20 minutes per week, over a two-week period, then three treatments per week for the following two weeks and finally in the last two weeks only two treatments per week are scheduled. This is the standard protocol for this kind of therapy and is not changed in any way for the participants of the MRI study. For the VW, the participants will sit on an electric wheelchair in front of a canvas with an integrated camera. The camera films the participant's head and trunk, which are then projected on the canvas, overlapping with the recording of the feet of an actor walking. This way the participants will see themselves walk through a forest from a third-person view. To improve the embodiment, the participants will be asked to swing their arms in the rhythm of the gait and imagine that they are walking themselves through the forest. In addition to this, the chair moves minimally in the frontal plane to imitate the natural movements of the pelvis while walking.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 10, 2023
• Est. primary completion date: January 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Passed neurological, physiotherapeutic and psychological assessments and team decision to take part on VW

• Age ? 18

• Traumatic SCI (> 1 year) confirmed by MRI or CT

• Neuropathic at or below level spinal cord injury pain for at least 3 months diagnosed by a neurologist following the CanPain Clinical Practice Guidelines and ISCIP classification

• Good German skills (understand questionnaires and instructions)

• Ability to draw with a pen

• Ability to swing the arms

Exclusion Criteria:

• Claustrophobia

• Non-acceptance of the paraplegia

• Psychiatric disorders

• Epilepsy

• Other neurological, psycho-logical or cognitive impairments

• Pregnancy

• Spasticity that would interfere with MRI

• Extensive dose of opioids

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain
• Spinal Cord Injuries
• Wounds and Injuries

Locations

Country	Name	City	State
Switzerland	Swiss Paraplegic Centre; Centre for pain medicine	Nottwil	Lucerne

Sponsors (2)

Lead Sponsor	Collaborator
Swiss Paraplegic Research, Nottwil	Haute Ecole de Santé Vaud

Country where clinical trial is conducted

Switzerland, 

References & Publications (30)

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sociodemographic and clinical characteristics	Collected during clinical routine: age, sex, pain duration, age at injury, lesion level, comorbidities, concomitant injuries, pain severity, pain distribution and quality, medication, education level, workability, functional impairment, motor imagery capacity and habits like smoking, quantity of alcohol or caffeine-containing potables.	At the beginning and at follow up.
Primary	Change of N-Acetyl-Aspartate in the anterior cingulate cortex	Non-invasive MRI-based metabolic marker measured under various conditions (resting state, painful images, non-painful images)	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Change of Choline	Non-invasive MRI-based metabolic marker (resting state, painful images, non-painful images)	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Alteration of Creatine	Non-invasive MRI-based metabolic marker	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Alteration of myo-Inositol	Non-invasive MRI-based metabolic marker	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	BOLD signal changes during task-based and resting state functional MRI	Task-based and resting state functional MRI sequences are applied and BOLD signal changes are examined. A whole-brain and seed-based connectivity analysis are used and linked to pain processing and perception.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Pain diary	A pain diary using the numeric pain rating scale from 0 = "no pain at all" to 10 = "worst imaginable pain", to assess pain intensity during the course of the study and in follow-up.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Pain description list	Questionnaire containing 12 descriptions of pain to assess the quality of pain (how the pain is perceived) Patients have to rate each description on a scale ranging from 0 = "completely disagree" to 3 = "fully agree" Items 1 to 8 are only descriptively evaluated. The sum of items 9 to 12 is the affective score whereas a high value is indicating a high affective burden and a low value is equal to a low affective burden.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Chronic pain grading scale	Questionnaire to assess the severity of chronic pain and its impact on daily activities containing 7 items that must be rated on a NRS ranging from 0 = "no pain", "no limitation"; to 10 = "worst imaginable pain"/limitation". Higher values thus indicating more pain/limitation.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	The Marburg questionnaire on habitual health findings	Questionnaire to assess general wellbeing containing 7 items that have to be rated on a rating scale ranging from 0 = "completely disagree" to 5 = "completely agree". A high score in this questionnaire indicates high well-being.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	WHO-QoL-BREF	Questionnaire containing 26 items to assess quality of life rated on a rating scale ranging from 1 = "very bad"/"very unhappy"/"not at all"/"never" to 5 = "very good"/"very happy"/"absolutely"/"always". Depending on the statements the scores have to be inversed to calculate the score. Higher scores indicate better quality of life. There are four domain scores that result from this questionnaire: physical domain, psychological domain, social relationships domain and environment domain.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Pain catastrophizing scale	Questionnaire containing 13 items/statements to assess pain catastrophizing on a rating scale ranging from 0 = "never true" to 4 = "always true". A high score indicates a high degree of pain catastrophizing.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Questions about pain chronification	Questionnaire to assess pain chronification consisting of ten questions. The single questions help to classify the stadium of pain chronification ranging from stadium I = mild chronification to stadium III = heavy chronification.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	SCI independence measure III - self-reported version	Questionnaire addressing the functional impairment including 17 items assessing the grade of necessary aid versus ability to do it on their own for specific daily activities with ratings ranging from 0 = "not able to do a task" to 8 = "no or minimal aid". The higher the score the more independent the person.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Depression, Anxiety & Stress Scale	Questionnaire to assess depression, anxiety and stress using 21 items rated on a scale from 0 = "absolutely disagree" or "never" to 3 = "strong agreement" or "most of the time". Because the items are negatively formulated a high score indicates a high grade of depression, anxiety or stress. Each domain score consists of 7 items.	Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Secondary	Patient Global Impression of Change	One question to assess the subjective global impression of change after the therapy. The choice options range from "very much better than before" to "very much worse than before" with "unchanged" as the middle/neutral value.	Two measurement time points: only T2 (six weeks after baseline) and T3 (ten weeks after baseline))

External Links

•   Declaration of Helsinki
•   Ordinance on Human Research with the Exception of Clinical trials (HRO), swiss law