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

March 7, 2024 updated by: Swiss Paraplegic Research, Nottwil

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

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.

Study Overview

Status

Completed

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Actual)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
    • Lucerne
      • Nottwil, Lucerne, Switzerland, 6207
        • Swiss Paraplegic Centre; Centre for pain medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Twelve individuals with SCI and NeP will be recruited at the Centre for Pain Medicine, Swiss Paraplegic Centre, Nottwil. A neurologist will check for inclusion and exclusion criteria.

Patients, who will be screened routineously as part of the ordinary clinical visit by a neurologist, a physiotherapist and a psychologist for their eligibility to take part in the clinical VW program, will additionally be screened for their participation in the intended study. These assessments include checking inclusion and exclusion criteria and a diagnosis using the SCI pain basic dataset 2.0.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of N-Acetyl-Aspartate in the anterior cingulate cortex
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of Choline
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
Alteration of Creatine
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Non-invasive MRI-based metabolic marker
Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Alteration of myo-Inositol
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
Non-invasive MRI-based metabolic marker
Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
BOLD signal changes during task-based and resting state functional MRI
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
Pain diary
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
Pain description list
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
Chronic pain grading scale
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
The Marburg questionnaire on habitual health findings
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
WHO-QoL-BREF
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
Pain catastrophizing scale
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
Questions about pain chronification
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
SCI independence measure III - self-reported version
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
Depression, Anxiety & Stress Scale
Time Frame: Three measurement time points: Baseline (T1), six weeks after baseline (T2), ten weeks after after baseline (T3)
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)
Patient Global Impression of Change
Time Frame: Two measurement time points: only T2 (six weeks after baseline) and T3 (ten weeks after baseline))
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))

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sociodemographic and clinical characteristics
Time Frame: At the beginning and at follow up.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Swiss Paraplegic Research, Nottwil

Collaborators

Haute Ecole de Santé Vaud

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 2021

Primary Completion (Actual)

January 10, 2023

Study Completion (Actual)

January 10, 2023

Study Registration Dates

First Submitted

September 13, 2021

First Submitted That Met QC Criteria

October 18, 2021

First Posted (Actual)

October 28, 2021

Study Record Updates

Last Update Posted (Actual)

March 8, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-13

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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