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

Multiple Sclerosis Clinical Trial

— PREFIMS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05003375
• Other study ID #: S63552
• Status: Recruiting
• Start date: October 15, 2020
• Est. completion date: September 1, 2021

Study information

• Verified date: August 2021
• Source: KU Leuven
• Contact: Daphne Kos, PhD
• Phone: +32496-107849
• Email: daphne.kos[@]kuleuven.be
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 1, 2021
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatigue
• Multiple Sclerosis
• Sclerosis
• Stress

Intervention

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

Locations

Country	Name	City	State
Belgium	KU Leuven, Department of Rehabilitation Sciences	Leuven
Belgium	National Multiple Sclerosis Center	Melsbroek

Sponsors (2)

Lead Sponsor	Collaborator
KU Leuven	National MS Center Melsbroek

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)