Physiological Responses in Experimentally Induced Cognitive Fatigue in People With Multiple Sclerosis (MS) (PREFIMS)

Physiological Responses in Experimentally Induced Cognitive Fatigue in People With Multiple Sclerosis (MS): a Feasibility Study

The current study will add to the current knowledge by combining several electrophysiological techniques to examine the relationship between physiological responses and cognitive fatigue and daily activity performance in a stress- and fatigue-inducing protocol.

The aims of this study are: 1) to evaluate the feasibility and usability of assessing physiological responses in an experimental set-up and 2) to investigate the association between physiological outcomes, experimentally induced stress and cognitive fatigue in people with multiple sclerosis (MS) and healthy controls.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Fatigue; Stress
• Intervention / Treatment: Behavioral: High-challenging cognitive protocol to provoke stress and (cognitive) fatigue

Detailed Description

In an experimental set-up participants (20 people with MS and 20 healthy controls) will perform a high-challenging cognitive protocol to provoke stress and (cognitive) fatigue.

Physiological responses (heart rate variability, skin conductance, body temperature) and brain activity (EEG) will be measured while resting (resting baseline), while speaking as normal (speaking baseline), during protocol performance and following the protocol (post-protocol).

Demographic and clinical characteristics, as well as levels of perceived fatigue, stress, pain, daily activity performance, quality of life and anxiety and depression will be assessed using medical records and questionnaires.

Feasibility and usability will be assessed in participants and researcher(s) by standardized questionnaires.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Daphne Kos, PhD; Phone Number: +32496-107849; Email: daphne.kos@kuleuven.be
• Study Contact Backup: Name: Niels Peeters, MSc; Phone Number: +32474296463; Email: daphne.kos@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • KU Leuven, Department of Rehabilitation Sciences
    • Contact: Daphne Kos, PhD; Email: daphne.kos@kuleuven.be
    • Contact: Niels Peeters, MSc; Email: niels.peeters@kuleuven.be
  • Melsbroek, Belgium
    • Recruiting
    • National Multiple Sclerosis Center
    • Contact: Sofie Ferdinand, Ba; Phone Number: +3225978690; Email: sofie.ferdinand@mscenter.be
    • Contact: Mieke D'hooge, MSc; Email: mieke.dhooge@mscenter.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A convenience sample of 20 people with currently stable multiple sclerosis (MS) between 18 and 55 years old and able to walk for 100m will be recruited from the National MS Center Melsbroek, as well as 20 age-matched healthy volunteers.

Description

Inclusion Criteria:

• diagnosis MS, Relapsing Remitting (RR) type (MS group)
• Expanded Disability Status Scale (EDSS) <6 (MS group)
• Dutch speaking
• normal or corrected vision
• feasible use of computer

Exclusion Criteria:

• relapse < 3 months (MS group)
• pregnancy
• relevant comorbidity (thyroid disease, diabetes, other neurological disorders, metabolic diseases, neuro-endocrine tumor(s)
• severe cognitive disability

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Multiple Sclerosis (MS); People with MS diagnosis, aged 18-55 years, Relapsing Remitting type, EDSS < 6.0, normal vision (if necessary corrected), Dutch speaking.	Behavioral: High-challenging cognitive protocol to provoke stress and (cognitive) fatigue; Baseline measurement is done in two parts: 1) resting for five minutes (no talking, no movement) and 2) speaking at normal pace (2 minutes). This is immediately followed by a measurement of the physiological response variables during the testing, in which the following protocol is performed in the order presented: 1) SDMT-NBack task-SDMT*-NBacktask**, 2) NBack task-SDMT-NBack task-SDMT. Participants will run either sequence to check for effects of the previous testing. During the conduct of the study, it will be ensured that half of the participants in each group followed Sequence 1 and the other half of the group followed Sequence 2. During all these measurements, the participant will sit at a table with a computer on which the tests are performed. *SDMT: Symbol Digit Modalities Test: see description in outcome measures **N-Back Task: see description in outcome measures
Healthy Controls (HC); Healthy controls without relevant health conditions (diabetes, thyroid diseases, neurological disorders), non-pregnant, aged 18-55 years, normal vision (if necessary corrected), Dutch speaking.	Behavioral: High-challenging cognitive protocol to provoke stress and (cognitive) fatigue; Baseline measurement is done in two parts: 1) resting for five minutes (no talking, no movement) and 2) speaking at normal pace (2 minutes). This is immediately followed by a measurement of the physiological response variables during the testing, in which the following protocol is performed in the order presented: 1) SDMT-NBack task-SDMT*-NBacktask**, 2) NBack task-SDMT-NBack task-SDMT. Participants will run either sequence to check for effects of the previous testing. During the conduct of the study, it will be ensured that half of the participants in each group followed Sequence 1 and the other half of the group followed Sequence 2. During all these measurements, the participant will sit at a table with a computer on which the tests are performed. *SDMT: Symbol Digit Modalities Test: see description in outcome measures **N-Back Task: see description in outcome measures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in heart rate variability (time-domain)	ECG monitoring will be done using the MindMedia NEXUS-10MKII.- Heart Rate Variability will be studied in a time- and frequency domain. For the time-domain following measures are studied: 1) the average normal-normal interval; 2) the standard deviation of normal-normal (SDNN); 3) the Root Mean Square of Successive Differences (RMSSD); 4) the percentage of adjacent normal-normal intervals with differences of more than 50miliseconds. (PNN50).	immediately post protocol (approx. 2 hours after baseline)
Change in heart rate variability (frequency-domain)	ECG monitoring will be done using the MindMedia NEXUS-10MKII.- Heart Rate Variability will be studied in a time- and frequency domain. For the frequency domain, the changes in the high frequency (HF) and low frequency (LF) will be studied and analysed.	immediately post protocol (approx. 2 hours after baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visual Analogue Scale (VAS) Momentary fatigue	Momentary fatigue experienced following the protocol using Visual Analogue Scale (VAS) (minimum 0- maximum 10), higher scores indicate higher fatigue.	immediately post protocol (approx. 2 hours after baseline)
Change in Visual Analogue Scale (VAS) Momentary pain	Momentary pain experienced following the protocol using Visual Analogue Scale (minimum 0- maximum 10), higher scores indicate higher pain.	immediately post protocol (approx. 2 hours after baseline)
Usefulness, Satisfaction, and ease of use Questionnaire (USE)	The USE is a self-report questionnaire in which 30 items in four dimensions (usefulness, ease of use, ease of learning and satisfaction) are answered on a 7-point Likert scale (1 = disagree, 7 = fully agree) and one not -answer option. Higher scores indicate higher satisfaction and usefulness.	post protocol (approx. 2 hours after baseline)
NASA Task Load Index (NASA-TLX)	The NASA-TLX is a self-report questionnaire that measures perceived work-related stress using six dimensions with a focus on mental stress: mental, physical and time-related stress, frustration and execution. The dimensions are assessed on the basis of a semantic differential scale (0-10). The six individual scores are converted to a global score by means of a "paired comparison task" in which "comparison cards" are used prior to the assessment. Higher scores indicate higher task load.	post protocol (approx. 2 hours after baseline)
Galvanic Skin Response (GSR)	For the monitoring of the GSR, the Mind Media NEXUS-10MKII will be used.; Two electrodes will be placed on the palmar side of the left manus. The first electrode is positioned on the phalanx medialis of the index, the second electrode is positioned on the phalanx medialis of the digitus annulare.; As the participants will not be exposed to abrupt changes in stimulus presentation, and no expected or unexpected changes in the environment will be present, the tonic Skin Conductance Level (SCL) will be analysed.	baseline
Galvanic Skin Response (GSR)	For the monitoring of the GSR, the Mind Media NEXUS-10MKII will be used.; Two electrodes will be placed on the palmar side of the left manus. The first electrode is positioned on the phalanx medialis of the index, the second electrode is positioned on the phalanx medialis of the digitus annulare.; As the participants will not be exposed to abrupt changes in stimulus presentation, and no expected or unexpected changes in the environment will be present, the tonic Skin Conductance Level (SCL) will be analysed, using mean microsiemens.	during protocol (approx. 1 hour after baseline)
Galvanic Skin Response (GSR)	For the monitoring of the GSR, the Mind Media NEXUS-10MKII will be used.; Two electrodes will be placed on the palmar side of the left manus. The first electrode is positioned on the phalanx medialis of the index, the second electrode is positioned on the phalanx medialis of the digitus annulare.; As the participants will not be exposed to abrupt changes in stimulus presentation, and no expected or unexpected changes in the environment will be present, the tonic Skin Conductance Level (SCL) will be analysed, using mean microsiemens.	immediately post protocol (approx. 2 hours after baseline)
Brain activity	• Electroencephalography (EEG): EEG monitoring will be done using the MindMedia NEXUS-10MKII.; Ten20 conductive paste for EEG is used in combination with Ag/AgCl disc electrodes.; A positive electrode will be placed on Cz according to the international 10-20 system, a negative electrode will be placed on the left earlobe, and the ground electrode for EEG and ECG measurement will be placed on the right earlobe. EEG measures: - The impact of the cognitive fatigue and stress inducing protocol on alpha, beta, delta, and there frequency bands will be studied.	baseline
Brain activity	• Electroencephalography (EEG): EEG monitoring will be done using the MindMedia NEXUS-10MKII.; Ten20 conductive paste for EEG is used in combination with Ag/AgCl disc electrodes.; A positive electrode will be placed on Cz according to the international 10-20 system, a negative electrode will be placed on the left earlobe, and the ground electrode for EEG and ECG measurement will be placed on the right earlobe. EEG measures: - The impact of the cognitive fatigue and stress inducing protocol on alpha, beta, delta, and there frequency bands will be studied.	during protocol (approx. 1 hour after baseline)
Brain activity	• Electroencephalography (EEG): EEG monitoring will be done using the MindMedia NEXUS-10MKII.; Ten20 conductive paste for EEG is used in combination with Ag/AgCl disc electrodes.; A positive electrode will be placed on Cz according to the international 10-20 system, a negative electrode will be placed on the left earlobe, and the ground electrode for EEG and ECG measurement will be placed on the right earlobe. EEG measures: - The impact of the cognitive fatigue and stress inducing protocol on alpha, beta, delta, and there frequency bands will be studied.	immediately post protocol (approx. 2 hours after baseline)
Respiration	Respiration set up: The mind media NEXUS-10 MKII will be used for respiration measurement.; An elastic band with sensor will be worn around the trunk at height of the umbilicus. Respiration measures: Data will solely cover mechanical aspects of breathing.; Only the respiration rate will be taken into analyses to study relations with previous neurophysiological measures.; Also the breathing rate (BRPM) per minute will be analysed.	baseline
Respiration	Respiration set up: The mind media NEXUS-10 MKII will be used for respiration measurement.; An elastic band with sensor will be worn around the trunk at height of the umbilicus. Respiration measures: Data will solely cover mechanical aspects of breathing.; Only the respiration rate will be taken into analyses to study relations with previous neurophysiological measures.; Also the breathing rate (BRPM) per minute will be analysed.	during protocol (approx. 1 hour after baseline)
Respiration	Respiration set up: The mind media NEXUS-10 MKII will be used for respiration measurement.; An elastic band with sensor will be worn around the trunk at height of the umbilicus. Respiration measures: Data will solely cover mechanical aspects of breathing.; Only the respiration rate will be taken into analyses to study relations with previous neurophysiological measures.; Also the breathing rate (BRPM) per minute will be analysed.	immediately post protocol (approx. 2 hours after baseline)
Decline in Symbol Digit Modalities Test	The Symbol Digit Modalities Test (SDMT) Performance; The SDMT is frequently used in the normal treatment and follow up of people with MS. Therefore, a customized version for this study is developed.; Participants are shown one file with at the top a row as example consisting of symbols with related numbers. Beneath this row, a couple of rows with symbols are shown. The participant has to link the number to the specific symbol according to the example row. This as fast as possible within 90 seconds. Scores; A total score consisting of the total amount of correct answers will be determined.; The SDMT will be divided in three equal parts of 30 seconds.; For part1 part2, and part3 a correct score will be determined.; Additionally, a cognitive fatigability score is determined: the difference between part3 versus part1.	immediately post protocol (approx. 2 hours after baseline)
Decline in N-Back Task	The N-Back Task (NBT) Performance: The participants are shown a presentation of a series of letters. The participants have to respond with 'yes' whenever the same letter appeared as two letters previously.; The participants perform two versions of this: with a 2- and 1-second interstimulus interval. Scores: A total score consisting of the total amount of correct answers is determined.; The NBT is then divided in three equal parts. For part1, part2, and part3, a total correct score is determined.; Additionally, a cognitive fatigability score (i.e. difference between part3 and part1) is determined.	immediately post protocol (approx. 2 hours after baseline)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Fatigue Impact Scale (MFIS)	The MFIS is a self-report questionnaire used to measure the perceived impact of fatigue on physical, cognitive and psychosocial functioning. The participant answers 21 items on the basis of a 5-point Likert scale (0 = never; 5 = almost always). A higher score on the subscales (physical dimension: 0-36; cognitive dimension: 0-40; psychosocial functioning: 0-8) or in the total score represents a higher degree of fatigue.	baseline
Perceived Stress Scale (PSS)	Questionnaire on perceived stress in daily life (14 items) The Perceived Stress Scale (PSS) is a self-report questionnaire to measure the perceived stress. In 14 items perceived stress is judged by taking into account the previous month's experiences.. Scoring is done using a 5-point Likert scale (0 = never; 4 = very often), with a maximum score (56) representing a higher degree of perceived stress.	baseline
Hospital Anxiety and Depression Scale (HADS)	Self-report questionnaire of depression and anxiety (14 items) The HADS is aimed at assessing anxiety and depression in a non-psychiatric setting, without questioning physical complaints such as fatigue.The HADS is a self-report questionnaire of 14 items that are answered on the basis of an ordinal scale with four answer options (0-3). Depression and anxiety subscale scores range from 0-21, with higher scores indicating increased depression or anxiety, respectively.	baseline
Life Balance Inventory (LBI)	LBI is a self-report assessment instrument containing 53 activities and on a dichotomous scale of yes/no, people have to answer, whether or not they do the activity or want to do the activity. For each item scored 'yes', participants have to rate their satisfaction with the amount of time they have spent doing that activity in the past month compared to the amount of time they wanted to do the activity. The possible answers are: "always less than I want (1), sometimes less than I want (2), about right for me (3), sometimes more than I want (2), always more than I want (1)". The LBI contains four subscales: (1) Health subscale (ex. Relaxing, getting regular exercise, …), (2) Relationship subscale (ex. Doing things with friends, partner, …), (3) Identity subscale (ex. Taking care of your appearance, participating in religious events, …), (4) Challenge/interest subscale (ex. Working for pay, making music, …). Higher scores reflect better life balance.	baseline

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: National MS Center Melsbroek
• Investigators: Principal Investigator: Daphne Kos, PhD, KU Leuven

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2020
• Primary Completion (ANTICIPATED): August 30, 2021
• Study Completion (ANTICIPATED): September 1, 2021

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (ACTUAL): August 12, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2021
• Last Update Submitted That Met QC Criteria: August 5, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: fatigability; cognitive fatigue; cognitive fatigability
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Fatigue
• Other Study ID Numbers: S63552

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No