Trial Outcomes & Findings for Prospective Case Series to Refine Standalone Cognitive Behavioral Therapy Components for Multiple Sclerosis Fatigue (NCT NCT05848323)

NCT ID: NCT05848323

Last Updated: 2025-11-26

Results Overview

Intervention Acceptability will be measured with the Acceptability of Intervention Measure (AIM). When assessed via online survey, responses from the Intervention Acceptability items are averaged to create a mean score \[1-5\]. A higher score indicates more agreement with intervention acceptability while a lower score indicates less agreement with intervention acceptability.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

21 participants

Primary outcome timeframe

Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Results posted on

2025-11-26

Participant Flow

Participants were recruited from a multiple sclerosis comprehensive care center from October 2023 to August 2024.

Thirty individuals were screened for eligibility. Seven individuals were ineligible due to MS relapse in prior 30 days (n=1), disease modifying therapy change in prior 3 months (n=1), score lower than 4 on the Fatigue Severity Scale (n=3), significant cognitive impairment (n=1), and no MS diagnosis (n=1). One individual declined to participant due to the time commitment for study participation. One individual was excluded because research staff were unable to contact them after several attempts

Participant milestones

Participant milestones
Measure
Relaxation Training
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Overall Study
STARTED
7
7
7
Overall Study
COMPLETED
7
7
7
Overall Study
NOT COMPLETED
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Prospective Case Series to Refine Standalone Cognitive Behavioral Therapy Components for Multiple Sclerosis Fatigue

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Total
n=21 Participants
Total of all reporting groups
Age, Continuous
48.3 years
STANDARD_DEVIATION 12.3 • n=492 Participants
47.9 years
STANDARD_DEVIATION 13.4 • n=492 Participants
46.6 years
STANDARD_DEVIATION 14.9 • n=984 Participants
47.6 years
STANDARD_DEVIATION 12.9 • n=3 Participants
Sex: Female, Male
Female
4 Participants
n=492 Participants
5 Participants
n=492 Participants
5 Participants
n=984 Participants
14 Participants
n=3 Participants
Sex: Female, Male
Male
3 Participants
n=492 Participants
2 Participants
n=492 Participants
2 Participants
n=984 Participants
7 Participants
n=3 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=492 Participants
0 Participants
n=492 Participants
0 Participants
n=984 Participants
0 Participants
n=3 Participants
Race (NIH/OMB)
Asian
0 Participants
n=492 Participants
0 Participants
n=492 Participants
2 Participants
n=984 Participants
2 Participants
n=3 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=492 Participants
0 Participants
n=492 Participants
0 Participants
n=984 Participants
0 Participants
n=3 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=492 Participants
1 Participants
n=492 Participants
2 Participants
n=984 Participants
4 Participants
n=3 Participants
Race (NIH/OMB)
White
6 Participants
n=492 Participants
4 Participants
n=492 Participants
3 Participants
n=984 Participants
13 Participants
n=3 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=492 Participants
1 Participants
n=492 Participants
0 Participants
n=984 Participants
1 Participants
n=3 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=492 Participants
1 Participants
n=492 Participants
0 Participants
n=984 Participants
1 Participants
n=3 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=492 Participants
1 Participants
n=492 Participants
0 Participants
n=984 Participants
2 Participants
n=3 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants
n=492 Participants
6 Participants
n=492 Participants
7 Participants
n=984 Participants
19 Participants
n=3 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=492 Participants
0 Participants
n=492 Participants
0 Participants
n=984 Participants
0 Participants
n=3 Participants
Region of Enrollment
United States
7 Participants
n=492 Participants
7 Participants
n=492 Participants
7 Participants
n=984 Participants
21 Participants
n=3 Participants

PRIMARY outcome

Timeframe: Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Intervention Acceptability will be measured with the Acceptability of Intervention Measure (AIM). When assessed via online survey, responses from the Intervention Acceptability items are averaged to create a mean score \[1-5\]. A higher score indicates more agreement with intervention acceptability while a lower score indicates less agreement with intervention acceptability.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Intervention Acceptability
4.36 Units on a scale
Standard Deviation 0.70
4.64 Units on a scale
Standard Deviation 0.48
4.68 Units on a scale
Standard Deviation 0.59

PRIMARY outcome

Timeframe: Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Intervention Appropriateness will be measured with the Intervention Appropriateness Measure (IAM). When assessed via online survey, responses from the Intervention Appropriateness items are averaged to create a mean score \[1-5\]. A higher score indicates more agreement with intervention appropriateness while a lower score indicates less agreement with intervention appropriateness.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Intervention Appropriateness
4.14 Units on a scale
Standard Deviation 0.57
4.25 Units on a scale
Standard Deviation 0.74
4.25 Units on a scale
Standard Deviation 0.78

PRIMARY outcome

Timeframe: Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Intervention Feasibility will be measured with the Feasibility of Intervention Measure (FIM). When assessed via online survey, responses from the Intervention Feasibility items are averaged to create a mean score \[1-5\]. A higher score indicates more agreement with intervention feasibility while a lower score indicates less agreement with intervention feasibility.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Intervention Feasibility
4.46 Units on a scale
Standard Deviation 0.57
4.39 Units on a scale
Standard Deviation 0.61
4.42 Units on a scale
Standard Deviation 0.66

SECONDARY outcome

Timeframe: Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Fatigue will be measured by the Modified Fatigue Impact Scale. This is a 21-item self-report questionnaire assessing fatigue-related symptoms in the previous four weeks via 5-point Likert-type scale. It yields a total score (range: 0-84) and a higher score indicates greater fatigue.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Fatigue
Pre-treatment
44.29 Units on a scale
Standard Deviation 11.13
49.38 Units on a scale
Standard Deviation 9.74
54.71 Units on a scale
Standard Deviation 20.15
Fatigue
Post-treatment
36.14 Units on a scale
Standard Deviation 10.09
34.14 Units on a scale
Standard Deviation 12.27
37.29 Units on a scale
Standard Deviation 13.10

SECONDARY outcome

Timeframe: Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Patient Reported Outcomes Measurement Information System Short Form - Ability to Participate in Social Roles and Activities (PROMIS-SRA; Hahn et al., 2010). The 8-item short form version of the PROMIS-SRA assesses the perceived ability to perform one's usual social roles and activities. Items are rated on a 5-point Likert-type scale. Raw summed scores are converted to T-scores standardized to the U.S. general population (mean = 50, standard deviation = 10), with higher scores indicating better ability to participate in social roles and activities.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Participation in Social Roles and Activities
Pre-treatment
43.23 T-score
Standard Deviation 6.09
41.39 T-score
Standard Deviation 5.44
40.47 T-score
Standard Deviation 7.31
Participation in Social Roles and Activities
Post-treatment
43.64 T-score
Standard Deviation 4.42
46.30 T-score
Standard Deviation 7.52
44.04 T-score
Standard Deviation 4.28

SECONDARY outcome

Timeframe: Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Relaxation/Serenity will be measured by the Positive and Negative Affect Schedule Serenity Subscale. This is a 3-item self-report subscale of the Positive and Negative Affect Schedule assessing perceptions of feeling of calm, relaxed, and at ease over the previous week via a 5-point Likert-type scale. The summed total score ranges from 3-15 and a higher score indicates greater feelings of relaxation/serenity.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Relaxation/Serenity
Pre-treatment
9.00 Units on a scale
Standard Deviation 2.94
8.29 Units on a scale
Standard Deviation 1.38
9.57 Units on a scale
Standard Deviation 4.24
Relaxation/Serenity
Post-treatment
11.14 Units on a scale
Standard Deviation 1.95
10.00 Units on a scale
Standard Deviation 2.58
11.43 Units on a scale
Standard Deviation 1.62

SECONDARY outcome

Timeframe: Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Fatigue catastrophizing will be measured by the Fatigue Catastrophizing Scale. This is a 13-item self-report questionnaire assessing negative beliefs or expectations connected to one's perceptions of fatigue via a 5-point Likert-type scale. Summed total scores range from 0 to 52, and a higher score indicates greater fatigue catastrophizing.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Fatigue Catastrophizing
Pre-treatment
20.57 Units on a scale
Standard Deviation 9.14
18.86 Units on a scale
Standard Deviation 17.17
15.71 Units on a scale
Standard Deviation 12.79
Fatigue Catastrophizing
Post-treatment
19.29 Units on a scale
Standard Deviation 8.34
15.71 Units on a scale
Standard Deviation 11.25
11.43 Units on a scale
Standard Deviation 7.30

SECONDARY outcome

Timeframe: Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Behavioral activation will be measured by the Behavioral Activation for Depression Scale Short Form. This is a 9-item self-report measure. It assess the extent to which the respondent thinks they have engaged in pleasant and/or goal-directed activity over the past week via a 7-point Likert-type scale. Summed total scores range from 0 to 54, and a higher score indicates greater behavioral activation.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Behavioral Activation
Pre-treatment
27.14 Units on a scale
Standard Deviation 4.67
24.86 Units on a scale
Standard Deviation 8.11
29.14 Units on a scale
Standard Deviation 7.34
Behavioral Activation
Post-treatment
27.57 Units on a scale
Standard Deviation 10.21
35.43 Units on a scale
Standard Deviation 8.02
38.43 Units on a scale
Standard Deviation 6.60

SECONDARY outcome

Timeframe: Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).

This is a 18-item self-report questionnaire consisting of five subscales assessing cognitive responses (fear avoidance beliefs, embarrassment avoidance beliefs, symptom focusing) and behavioral responses (resting or avoidance of activity, all-or-nothing behavior) to fatigue one's connected to one's perceptions of fatigue via a 5-point Likert-type scale. The summed total subscale scores range from 0 to 12, and higher scores indicate a more negative response to fatigue.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Cognitive Behavioural Responses Questionnaire - Short Form
Fear Avoidance Beliefs at Pre-treatment
4.00 Units on a scale
Standard Deviation 2.31
5.57 Units on a scale
Standard Deviation 1.72
6.29 Units on a scale
Standard Deviation 3.55
Cognitive Behavioural Responses Questionnaire - Short Form
Fear Avoidance Beliefs at Post-treatment
4.00 Units on a scale
Standard Deviation 2.08
5.57 Units on a scale
Standard Deviation 1.62
4.86 Units on a scale
Standard Deviation 4.26
Cognitive Behavioural Responses Questionnaire - Short Form
Embarrassment Avoidance Beliefs at Pre-treatment
7.57 Units on a scale
Standard Deviation 3.69
6.29 Units on a scale
Standard Deviation 2.36
6.14 Units on a scale
Standard Deviation 4.06
Cognitive Behavioural Responses Questionnaire - Short Form
Embarrassment Avoidance Beliefs at Post-treatment
7.71 Units on a scale
Standard Deviation 4.39
6.14 Units on a scale
Standard Deviation 4.41
6.43 Units on a scale
Standard Deviation 3.69
Cognitive Behavioural Responses Questionnaire - Short Form
Symptom Focusing at Pre-treatment
7.14 Units on a scale
Standard Deviation 3.34
6.43 Units on a scale
Standard Deviation 2.15
6.00 Units on a scale
Standard Deviation 2.65
Cognitive Behavioural Responses Questionnaire - Short Form
Symptom Focusing at Post-treatment
6.57 Units on a scale
Standard Deviation 3.10
4.00 Units on a scale
Standard Deviation 3.83
4.71 Units on a scale
Standard Deviation 2.21
Cognitive Behavioural Responses Questionnaire - Short Form
Resting or Avoidance of Activity at Pre-treatment
4.14 Units on a scale
Standard Deviation 3.24
6.00 Units on a scale
Standard Deviation 3.16
7.29 Units on a scale
Standard Deviation 3.59
Cognitive Behavioural Responses Questionnaire - Short Form
Resting or Avoidance of Activity at Post-treatment
4.14 Units on a scale
Standard Deviation 3.58
5.00 Units on a scale
Standard Deviation 2.71
7.57 Units on a scale
Standard Deviation 3.26
Cognitive Behavioural Responses Questionnaire - Short Form
All-or-nothing Behavior at Pre-treatment
9.00 Units on a scale
Standard Deviation 2.58
10.00 Units on a scale
Standard Deviation 2.16
9.29 Units on a scale
Standard Deviation 2.29
Cognitive Behavioural Responses Questionnaire - Short Form
All-or-nothing Behavior at Post-treatment
8.29 Units on a scale
Standard Deviation 2.36
7.00 Units on a scale
Standard Deviation 2.38
7.43 Units on a scale
Standard Deviation 3.10

SECONDARY outcome

Timeframe: Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).

This is a single-item self-report scale that assess the perceived intervention-related change in one's activity limitations, symptoms, emotions, and overall quality of life via 7-point Likert-type scale. The score ranges from 0 to 6 and a higher score indicates greater perceived change.

Outcome measures

Outcome measures
Measure
Relaxation Training
n=7 Participants
Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.
Behavioral Activation
n=7 Participants
Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).
Cognitive Therapy
n=7 Participants
Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).
Global Impression of Change
4.43 Units on a scale
Standard Deviation 0.98
4.29 Units on a scale
Standard Deviation 1.25
4.43 Units on a scale
Standard Deviation 1.13

Adverse Events

Behavioral Activation

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Relaxation Training

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Cognitive Therapy

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Lindsey Knowles

University of Washington

Phone: 2067449640

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place