Cognitive Behavioral Therapy for Multiple Sclerosis Fatigue

Overseen By Dawn Ehde, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Washington

Disqualifiers: MS relapse, Suicidal ideation, Psychotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 8-16 weeks

112 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different types of cognitive-behavioral therapy to determine which ones reduce fatigue in people with multiple sclerosis (MS). It includes treatments such as relaxation training, behavioral activation (encouraging more activities), and cognitive therapy (altering negative thoughts). Participants will engage in sessions via phone or video chat to develop these skills. The trial seeks individuals who have experienced MS-related fatigue for at least three months and find it challenging to manage. As an unphased trial, this study provides a unique opportunity to explore innovative therapies that could enhance quality of life.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have changed your disease modifying medications in the past three months to be eligible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that relaxation training can greatly reduce tiredness in people with multiple sclerosis (MS). Research also shows that these techniques improve sleep and lower anxiety. Reports indicate that these methods are usually well-tolerated, with no major side effects.

Research on behavioral activation, adapted for MS, suggests it can lessen tiredness and assist with daily activities. This approach is considered safe and encourages involvement in meaningful activities.

Cognitive therapy, particularly cognitive behavioral therapy (CBT), has offered moderate short-term benefits in reducing tiredness for MS patients. Its positive effects can last up to a year, and participants generally respond well to it.

Overall, these therapies are considered safe because they are non-invasive and use mental and behavioral strategies to manage tiredness. They have been used successfully in other studies without significant safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for multiple sclerosis fatigue because they leverage cognitive behavioral therapy (CBT) techniques in a telehealth format, offering a fresh approach to managing the condition. Unlike standard treatments that often involve medications like amantadine or behavioral strategies focused solely on energy conservation, these therapies combine relaxation training, cognitive therapy, and behavioral activation, which are all delivered remotely. This not only provides a comprehensive, holistic approach to managing fatigue but also makes it more accessible to patients who may have mobility challenges or limited access to in-person therapies. The integration of telehealth allows for flexible scheduling and potentially broader reach, which is particularly beneficial for those living in remote areas.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis fatigue?

This trial will evaluate different components of cognitive behavioral therapy (CBT) for reducing fatigue in people with multiple sclerosis (MS). Participants may receive various combinations of relaxation training, behavioral activation, and cognitive therapy. Studies have shown that these therapies can help reduce fatigue in MS patients. Specifically, research indicates that relaxation techniques, such as progressive muscle relaxation, can significantly lower fatigue levels and improve quality of life. Behavioral activation lessens mental health symptoms and enhances daily activities. Evidence also supports that cognitive therapy effectively reduces MS-related fatigue in both the short and long term. Overall, these therapies show promise in managing fatigue, offering potential benefits for those living with MS. ^{1 2 6 7 8}

Who Is on the Research Team?

Lindsey Knowles, PhD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for adults with multiple sclerosis who experience fatigue. It's not specified, but typically participants should be in stable health aside from their MS and fatigue symptoms.

Inclusion Criteria

I have been diagnosed with multiple sclerosis.

Able to fluently converse and read in English

Able to comply with study procedures and complete self-report measures

Exclusion Criteria

I have had an MS flare-up in the last 30 days.

Current suicidal ideation with intent or plan as indicated by a score of ≥1 on the Patient Health Questionnaire-9 suicide item and further assessment via the Columbia Suicide Severity Rating Scale (although individuals with suicidal ideation but no intent or plan will be considered eligible)

Currently participating in another research study that could impact fatigue such as intervention studies targeting mood, energy management, exercise/physical activity, and diet (although participants can be screened for eligibility again once they have completed the other research study)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive telehealth CBT components including Relaxation Training, Behavioral Activation, and Cognitive Therapy for multiple sclerosis fatigue

8-16 weeks

4 sessions per component, delivered via phone or videoconference

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Patient-reported outcome measures collected at 3-month follow-up

What Are the Treatments Tested in This Trial?

Interventions

• Behavioral Activation
• Cognitive Therapy
• Relaxation Training

Trial Overview The study tests three different short therapies: cognitive therapy to change thought patterns, relaxation training to reduce stress, and behavioral activation to increase engagement in activities. The goal is to see which helps most with MS-related fatigue.

How Is the Trial Designed?

Group I: Relaxation Training, Behavioral Activation, and Cognitive Therapy Experimental Treatment 3 Interventions

4 sessions of telehealth Relaxation Training, 4 sessions of telehealth Behavioral Activation, and 4 sessions of telehealth Cognitive Therapy for multiple sclerosis fatigue that are derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. Each intervention involves 4, 30-60-minute sessions delivered via phone or videoconference.

Group II: Relaxation Training only Experimental Treatment 1 Intervention

A 4-session telehealth Relaxation Training intervention for multiple sclerosis fatigue that is derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. The intervention is based on the cognitive behavioral model of fatigue in multiple sclerosis. The intervention involves 4, 30-60-minute sessions including the following content a) education about fatigue in multiple sclerosis and the cognitive behavioral model of multiple sclerosis fatigue, b) treatment rationale, c) didactic and experiential training in relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, and autogenic relaxation, and d) goal setting and problem-solving barriers to integrate relaxation practices into daily routine.

Group III: Relaxation Training and Cognitive Therapy Experimental Treatment 2 Interventions

4 sessions of telehealth Relaxation Training and 4 sessions of telehealth Cognitive Therapy for multiple sclerosis fatigue that are derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. Each intervention involves 4, 30-60-minute sessions delivered via phone or videoconference.

Group IV: Relaxation Training and Behavioral Activation Experimental Treatment 2 Interventions

4 sessions of telehealth Relaxation Training and 4 sessions of telehealth Behavioral Activation for multiple sclerosis fatigue that are derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. Each intervention involves 4, 30-60-minute sessions delivered via phone or videoconference.

Group V: Cognitive Therapy only Experimental Treatment 1 Intervention

A 4-session telehealth Cognitive Therapy intervention for multiple sclerosis fatigue that is derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. The intervention is based on the cognitive behavioral model of fatigue in multiple sclerosis. The intervention involves 4, 30-60-minute sessions including the following content a) education about fatigue in multiple sclerosis, the cognitive behavioral model of multiple sclerosis fatigue, self-monitoring thoughts, and core beliefs, b) treatment rationale, c) labeling thoughts as helpful, unhelpful, or neutral, d) using distraction to cope with unhelpful thoughts, e) challenging and changing unhelpful thoughts, f) problem-solving barriers to coping with or changing unhelpful thoughts.

Group VI: Behavioral Activation only Experimental Treatment 1 Intervention

A 4-session telehealth Behavioral Activation intervention for multiple sclerosis fatigue that is derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. The intervention is based on the cognitive behavioral model of fatigue in multiple sclerosis. The intervention involves 4, 30-60-minute sessions including the following content a) education about fatigue in multiple sclerosis, the cognitive behavioral model of multiple sclerosis fatigue, and self-monitoring activity and energy, b) treatment rationale, c) identification of values/priorities to guide activities, d) activity planning, e) goal setting and problem-solving barriers to engaging in activities.

Group VII: Behavioral Activation and Cognitive Therapy Experimental Treatment 2 Interventions

4 sessions of telehealth Behavioral Activation and 4 sessions of telehealth Cognitive Therapy for multiple sclerosis fatigue that are derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. Each intervention involves 4, 30-60-minute sessions delivered via phone or videoconference.

Group VIII: No Treatment Active Control 1 Intervention

Participants in the "No Treatment" condition will not complete any component sessions and will complete assessments at baseline (within 1 month of randomization), at approximately 2 months after randomization (the weighted average of weeks of treatment in the other conditions), and 3-month follow-up (dated from randomization). Upon study completion, these participants will be offered the opportunity to complete a component of their choice (Relaxation Training, Behavioral Activation, or Cognitive Therapy).

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Fatigue is the most common symptom reported by people with multiple sclerosis (MS) and significantly affects their quality of life, making its early detection and management crucial.

Rehabilitative interventions, particularly aerobic exercise, have shown positive effects on managing fatigue in MS, while medications like amantadine may offer some benefits, though their efficacy lacks strong evidence from randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue and multiple sclerosis. Béthoux, F.[2006]

Cognitive Behavioral Therapy (CBT) significantly improved cognitive and behavioral factors related to fatigue in multiple sclerosis patients compared to Relaxation Training (RT), with 70 participants involved in the study.

Changes in negative beliefs about fatigue were found to mediate the reduction in fatigue severity, indicating that addressing these beliefs is crucial for the effectiveness of CBT, independent of mood improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which cognitions and behaviours mediate the positive effect of cognitive behavioural therapy on fatigue in patients with multiple sclerosis? Knoop, H., van Kessel, K., Moss-Morris, R.[2022]

Over 80% of multiple sclerosis (MS) patients experience fatigue, which significantly impacts their quality of life and employment, yet effective pharmacological treatments are limited and poorly understood.

A comprehensive, individualized treatment strategy for MS-related fatigue should include identifying comorbid conditions, utilizing specific assessment scales, and considering therapies such as exercise, cognitive behavioral therapy, and medications like alfacalcidol or fampridine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Berlin Treatment Algorithm: recommendations for tailored innovative therapeutic strategies for multiple sclerosis-related fatigue. Veauthier, C., Hasselmann, H., Gold, SM., et al.[2020]

Cognitive Behavioral Therapy (CBT) significantly reduces fatigue in patients with Multiple Sclerosis (MS) during treatment, with improvements linked to better fatigue perceptions, increased physical activity, and enhanced physical functioning.

Post-treatment, maintaining low fatigue levels is associated with continued focus on physical activity, concentration, and managing sleepiness, suggesting these factors are crucial for sustaining the benefits of CBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal mediation analysis. van den Akker, LE., Beckerman, H., Collette, EH., et al.[2019]

Cognitive behavior therapy (CBT) significantly reduced fatigue in patients with multiple sclerosis (MS) more than relaxation training (RT) over an 8-month period, with a large effect size of 3.03 for CBT compared to 1.83 for RT.

Both CBT and RT were effective in reducing fatigue to levels comparable to those of healthy individuals, indicating that both therapies can provide meaningful relief for MS-related fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of cognitive behavior therapy for multiple sclerosis fatigue. van Kessel, K., Moss-Morris, R., Willoughby, E., et al.[2022]

Blended cognitive behavioural therapy (CBT), which combines online modules with therapist support, was found to be non-inferior to traditional face-to-face CBT in reducing fatigue severity in 166 patients with multiple sclerosis, demonstrating its effectiveness as an alternative treatment.

The blended approach not only maintained treatment efficacy but also significantly reduced the time therapists spent with patients, making it a more efficient option without any reported harm related to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blended versus face-to-face cognitive behavioural therapy for severe fatigue in patients with multiple sclerosis: A non-inferiority RCT. de Gier, M., Beckerman, H., Twisk, J., et al.[2023]

A pilot randomized controlled trial involving 40 patients with Multiple Sclerosis demonstrated that the Internet-based cognitive behavior therapy program, MS Invigor8, significantly reduced fatigue severity and impact compared to standard care, with large treatment effects (d=1.19 for severity and d=1.02 for impact).

Participants in the MS Invigor8 group also experienced notable improvements in anxiety, depression, and overall quality of life, suggesting that this online intervention could be a clinically effective and cost-effective option for managing MS-related fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot randomised controlled trial of an Internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue. Moss-Morris, R., McCrone, P., Yardley, L., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37648439/

Long-term effectiveness of a cognitive behavioural therapy ... Conclusions: A 6-week CBT-based programme with four booster sessions is superior to standard care alone to treat MS-related fatigue in the long term (12 months ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1474442224003545

Comparative effectiveness of cognitive behavioural therapy ... Modafinil, CBT, and combination therapy were associated with similar reductions in the effects of multiple sclerosis fatigue at 12 weeks.

3. neurology.org neurology.org/doi/abs/10.1212/WNL.0000000000210860

The Efficacy of Cognitive Behavioral Therapy in Reducing ... Conclusions: CBT programs can effectively reduce MS-associated fatigue and maintain their effects for at least 12 months. Nonetheless, they can ...

4. mdpi.com mdpi.com/2813-3064/3/2/12

Behavioral Activation Therapy for Multiple Sclerosis We suggest that MS-adapted BAT reduces neuropsychiatric symptoms, neurocognitive impairment, social isolation, and impairment of activities of daily living.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06809192

Factorial Optimization Trial to Test Cognitive Behavioral ... This randomized controlled factorial trial will examine whether and how relaxation training, behavioral activation, and cognitive therapy improve fatigue and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2910465/

Fatigue in Multiple Sclerosis: Mechanisms, Evaluation, and ... Fatigue is considered to be one of the main causes of impaired quality of life among MS patients, independent of depression or disability.

7. sciencedirect.com sciencedirect.com/science/article/pii/S221103482400484X

Cognitive behavioural therapy for fatigue in patients with ... The study provides secondary evidence that CBT has moderate short-term and small long-term effects in reducing fatigue in patients with MS.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03621761

Cognitive Behavioral Therapy, Modafinil, or Both for ... Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep ...