Cognitive Behavioral Therapy for Insomnia in Multiple Sclerosis

(CALM Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Kansas Medical Center

Must not be taking: Benzodiazepines, Non-benzodiazepines, Melatonin

Disqualifiers: Sleep apnea, Severe depression, Severe anxiety, Alcohol abuse, Schizophrenia, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The incidence of insomnia is estimated to be as high as 90% in individuals with MS due to insomnia being underdiagnosed. Sleep disturbances in people with MS have been associated with reduced cognitive performance, physical function, psychological well-being, quality of life, and occupational function, as well as increased prevalence of fatigue, pain, depression, and anxiety. The objective of the proposed study is to determine the efficacy of cognitive behavioral therapy for insomnia (CBT-I) to improve insomnia symptoms (Aim 1) fatigue, and health-related quality of life (Aim 2) in individuals with multiple sclerosis compared to an active control group, and to determine the characteristics of participants that predict improvement in sleep outcomes (Exploratory Aim 3).

Do I need to stop my current medications for this trial?

The trial requires that you are not currently taking benzodiazepines, non-benzodiazepines, or melatonin supplements or agonists for insomnia. If you are taking these, you would need to stop before participating.

What data supports the effectiveness of the treatment Cognitive Behavioral Therapy for Insomnia (CBT-I) in individuals with Multiple Sclerosis (MS)?

Research shows that Cognitive Behavioral Therapy for Insomnia (CBT-I) is effective in improving sleep quality and reducing fatigue in individuals with Multiple Sclerosis (MS). Digital versions of CBT-I (dCBT-I) have also been found to be effective, making it easier for people with MS to access the treatment, especially those with mobility issues or living in remote areas. ^{1 2 3 4 5}

Is Cognitive Behavioral Therapy for Insomnia safe for humans?

Cognitive Behavioral Therapy for Insomnia (CBT-I), including its digital version (dCBT-I), has been studied in various trials and is generally considered safe for humans. It is recommended as a first-line treatment for insomnia and has been shown to improve sleep quality without significant safety concerns. ^{1 3 5 6 7}

How is Cognitive Behavioral Therapy for Insomnia (CBT-I) different from other treatments for insomnia in multiple sclerosis?

CBT-I is unique because it can be delivered through a web-based application, making it accessible for individuals with multiple sclerosis who have mobility issues, experience fatigue, or live in rural areas. This digital approach allows for flexible and convenient treatment, which is particularly beneficial for those with MS. ^{1 2 4 8 9}

Research Team

Eligibility Criteria

This trial is for individuals aged 18-65 with relapsing-remitting or secondary progressive Multiple Sclerosis who experience insomnia symptoms at least three nights a week for the past three months. Participants should have mild-to-moderate disability, be English-speaking, and have internet access plus a suitable device.

Inclusion Criteria

≥31 on modified Telephone Interview of Cognitive Status

Has a high school diploma or equivalent

≥10 on Insomnia Severity Index

Exclusion Criteria

Current or history (up to 2 years) of alcohol or drug abuse as indicated by DSM-5 criteria

Severe mental illness such as schizophrenia or bipolar disorder

Severe neurological or sensory impairments that would interfere significantly with testing

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cognitive behavioral therapy for insomnia (CBT-I) or sleep and lifestyle education once a week for 6 weeks via video conferencing

6 weeks

6 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at baseline, Week 6, and Month 6

6 months

Treatment Details

Interventions

• Cognitive Behavioral Therapy for Insomnia (Behavioural Intervention)

Trial Overview The study aims to test if Cognitive Behavioral Therapy for Insomnia (CBT-I) can improve sleep, reduce fatigue, and enhance quality of life in MS patients compared to an active control group that receives only sleep and lifestyle education.

Participant Groups

Group I: Cognitive behavioral therapy for insomnia Experimental Treatment 1 Intervention

1x/week, 6-week 45-60 min one-one-one manualized program via video conferencing (HIPAA-compliant Zoom) with a trained research assistant that includes time in bed restriction, stimulus control, relaxation strategies, cognitive restructuring, and sleep health promotion education.

Group II: Sleep and lifestyle education Active Control 1 Intervention

1x/week, 6 weekly 45-60 min one-on-one program via video conferencing (HIPAA-compliant Zoom) with a trained research assistant that includes gentle stretching activities for major muscle groups accompanied by sleep and lifestyle education.

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Dr. Steve Stites

University of Kansas Medical Center

Chief Executive Officer

MD from University of Kansas School of Medicine

Dr. Matthias Salathe

University of Kansas Medical Center

Chief Medical Officer

MD from University of Kansas School of Medicine

Findings from Research

A study involving 41 individuals with multiple sclerosis (MS) demonstrated that a 6-week Web-based cognitive behavioral therapy for insomnia (CBT-I) program significantly improved insomnia severity, sleep quality, and anxiety, making it a feasible treatment option for those with mobility issues or living in remote areas.

The Web-based CBT-I program was effective in enhancing sleep outcomes, with notable improvements in depression and fatigue observed only in the group that received the program without additional telephone support, suggesting that the online format alone can be beneficial for managing insomnia in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Treatment Effect of a Web-Based Cognitive Behavioral Therapy for Insomnia Program in Individuals with Multiple Sclerosis: A Pilot Randomized Controlled Trial. Siengsukon, CF., Beck, ES., Drerup, M.[2022]

Cognitive Behavioral Therapy for Insomnia (CBT-I) improved sleep efficiency and reduced time in bed for individuals with multiple sclerosis, as measured by both sleep logs and actigraphy in a study of 25 participants.

The results suggest that CBT-I can enhance sleep outcomes in people with MS, but further research with a larger sample size is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Cognitive Behavioral Therapy for Insomnia on Sleep Log and Actigraphy Outcomes in People with Multiple Sclerosis: A Secondary Analysis. Williams-Cooke, C., LeSuer, L., Drerup, M., et al.[2022]

Digital cognitive behavioral therapy (dCBT) significantly improves functional health, psychological well-being, and sleep-related quality of life in individuals with insomnia, based on a study of 1711 participants over 24 weeks.

The reduction in insomnia symptoms was a key factor mediating these improvements, highlighting that dCBT effectively addresses both daytime and nighttime issues related to poor sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Digital Cognitive Behavioral Therapy for Insomnia on Health, Psychological Well-being, and Sleep-Related Quality of Life: A Randomized Clinical Trial. Espie, CA., Emsley, R., Kyle, SD., et al.[2023]

Individuals with multiple sclerosis (MS) experience sleep disorders, particularly insomnia, at a rate 3-5 times higher than the general population, which significantly contributes to fatigue, a major symptom of MS.

Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for insomnia in MS patients, and this review discusses how to adapt standard insomnia treatments to better suit the unique needs of individuals with MS, considering their level of disability and other health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Approaches to Insomnia and Fatigue in Patients with Multiple Sclerosis. Drerup, M., Roth, A., Kane, A., et al.[2021]

Digital cognitive behavior therapy for insomnia (dCBT-I) significantly improves sleep quality in patients with insomnia, particularly in those with anxiety disorders, as shown in a study of 6,002 patients over a 12-week period.

Patients receiving dCBT-I monotherapy and those with combined therapy showed notable improvements in sleep quality, with the most significant changes observed in the anxiety group, indicating that dCBT-I is a practical and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Digital cognitive behavior therapy for insomnia improving sleep quality: a real-world study. Liang, S., Mao, H., Yang, J., et al.[2022]

Digital cognitive behavioural therapy for insomnia (dCBT-I) significantly reduces insomnia severity, with a mean difference of -5.00 on the Insomnia Severity Index (ISI) immediately after treatment, based on a meta-analysis of 33 studies involving nearly 9,400 participants.

The benefits of dCBT-I are sustained over time, showing continued improvement at both short-term (4 weeks to 6 months) and 1-year follow-ups, making it a promising alternative to traditional face-to-face therapy, which, while slightly more effective, falls within a non-inferiority margin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of digital cognitive behavioural therapy for insomnia: a meta-analysis of randomised controlled trials. Soh, HL., Ho, RC., Ho, CS., et al.[2021]

Cognitive Behavioral Therapy for Insomnia (CBT-I) is feasible for individuals with multiple sclerosis (MS) and shows promising improvements in insomnia severity, sleep quality, and symptoms of fatigue and depression, based on a pilot study with 33 participants.

The study found that while all groups improved their insomnia symptoms, only the CBT-I group showed significant enhancements in sleep self-efficacy and depression, suggesting that CBT-I may offer unique benefits beyond general sleep education.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and treatment effect of cognitive behavioral therapy for insomnia in individuals with multiple sclerosis: A pilot randomized controlled trial. Siengsukon, CF., Alshehri, M., Williams, C., et al.[2021]

In a study of 127 multiple sclerosis patients with depression, the prevalence of insomnia was found to be very high at 78% before treatment, but significantly decreased to 43% after a 16-week psychotherapy intervention, indicating that targeted therapy can effectively reduce insomnia symptoms.

Insomnia was closely linked to depression and anxiety, and patients with ongoing insomnia after treatment were more likely to experience severe multiple sclerosis symptoms and lower quality of life, suggesting that additional treatments specifically for insomnia may be necessary alongside psychological interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of psychotherapy on insomnia symptoms in patients with depression and multiple sclerosis. Baron, KG., Corden, M., Jin, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Feasibility and Treatment Effect of a Web-Based Cognitive Behavioral Therapy for Insomnia Program in Individuals with Multiple Sclerosis: A Pilot Randomized Controlled Trial. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

The Impact of Cognitive Behavioral Therapy for Insomnia on Sleep Log and Actigraphy Outcomes in People with Multiple Sclerosis: A Secondary Analysis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effect of Digital Cognitive Behavioral Therapy for Insomnia on Health, Psychological Well-being, and Sleep-Related Quality of Life: A Randomized Clinical Trial. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Therapeutic Approaches to Insomnia and Fatigue in Patients with Multiple Sclerosis. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Digital cognitive behavior therapy for insomnia improving sleep quality: a real-world study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Digital Cognitive Behavioral Therapy vs Medication Therapy Among Patients With Insomnia. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of digital cognitive behavioural therapy for insomnia: a meta-analysis of randomised controlled trials. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Feasibility and treatment effect of cognitive behavioral therapy for insomnia in individuals with multiple sclerosis: A pilot randomized controlled trial. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Impact of psychotherapy on insomnia symptoms in patients with depression and multiple sclerosis. [2022]