Efficacy of Cognitive Behavioral Therapy for Insomnia to Treat Insomnia Symptoms in Individuals With Multiple Sclerosis (CALM)

Efficacy of Cognitive Behavioral Therapy for Insomnia to Treat Insomnia Symptoms and Fatigue in Individuals With Multiple Sclerosis

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).

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Insomnia
• Intervention / Treatment: Behavioral: Cognitive behavioral therapy for insomnia; Behavioral: Sleep and lifestyle education

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Catherine Siengsukon, PhD; Phone Number: 913-588-6913; Email: csiengsukon@kumc.edu
• Study Contact Backup: Name: Eryen Nelson, MPH; Phone Number: 913-945-7349; Email: enelson5@kumc.edu

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-65 years old
• Diagnosis of relapsing-remitting or secondary progressive MS based on established guidelines20 and verified by their neurologist
• Mild-to-moderately severe disability (≤ 6 on Patient Determined Disability Steps (PDDS) scale)
• Report of difficulty falling asleep, maintaining sleep, or waking up too early at least 3 nights/week for the past 3 months with significant distress and impact on function despite adequate opportunity for sleep and not due to other sleep disorders as indicated in the DSM-5
• ≥10 on Insomnia Severity Index
• English speaking
• ≥31 on modified Telephone Interview of Cognitive Status23
• Has a high school diploma or equivalent to serve as a proxy measurement of reading ability to ensure adequate reading ability to participate in the study
• Report having access to internet service or a data plan and access to a computer, tablet, or smart phone

Exclusion Criteria:

• Known untreated sleep disorder (such as sleep apnea or restless legs syndrome)
• >3 on STOP BANG indicating increased risk of sleep apnea
• Restless legs syndrome as determined by RLS-Diagnosis Index
• Circadian rhythm sleep-wake disorder as determined by the Sleep Disorders-Revised
• Parasomnia as determined by the Sleep Disorders-Revised
• Currently taking benzodiazepines, non-benzodiazepines, or melatonin supplements or agonists for insomnia
• Score of ≥20 on the Patient Health Questionnaire (PHQ-9) indicating severe depression or endorsement of suicidal ideation (answer 1, 2 or 3 on #9 of the PHQ-9)
• Score of ≥15 on the Generalized Anxiety Disorder (GAD-7) indicating severe anxiety
• Current or history (up to 2 years) of alcohol or drug or alcohol abuse as indicated by DSM-5 criteria
• History of other nervous system disorder such as stroke or Parkinson's disease
• Currently pregnant or intending to become pregnant in the next 6 months
• Severe mental illness such as schizophrenia or bipolar disorder
• Severe neurological or sensory impairments that would interfere significantly with testing
• Relapse and/or corticosteroid use in the past 8 weeks
• History of (within 5 years) or currently conducting overnight shift work including hours of midnight-4am
• Currently receiving a behavioral sleep health intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive behavioral therapy for insomnia; 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.	Behavioral: Cognitive behavioral therapy for insomnia; The general sessions outlines are as follows with each session: Session 1: determine treatment plan, set up sleep schedule and stimulus control, discuss strategies for how to stay awake to prescribed hour and what to do if wake up in middle of night, sleep hygiene education Session 2: continue upward titration of total sleep time, review sleep hygiene; introduce diaphragmatic breathing Session 3: continue upward titration of total sleep time, introduce mindfulness Session 4: continue upward titration of total sleep time, introduce progressive muscle relaxation Session 5: continue upward titration of total sleep time, discuss negative sleep beliefs Session 6: assess global treatment gains, discuss relapse prevention
Active Comparator: Sleep and lifestyle education; 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.	Behavioral: Sleep and lifestyle education; The general sessions outlines are as follows with each session: Session 1: Basic sleep education, stretching exercises Session 2: Sleep hygiene education (environmental factors & sleep positions), stretching exercises Session 3: Sleep hygiene education (lifestyle factors), stretching exercises Session 4: Diet recommendations, stretching exercises Session 5: Exercises recommendations, stretching exercises Session 6: Discus maintaining achievements & preventing relapses, stretching exercises

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insomnia Severity Index (ISI)	The ISI consists of 7 questions, each rated on a 0-4 scale. The range of scores on the ISI is 0-28, with a score of ≥ 10 suggesting clinical insomnia. The lower the score the less severe insomnia.	baseline, Week 6, Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pittsburgh Sleep Quality Index (PSQI)	The PSQI consists of 9 items within 7 sleep categories. The 7 sleep category scores are summed to form a single global score ranging from 0-21. A global score of >5 reflects poor sleep quality.	baseline, Week 6, Month 6
Epworth Sleepiness Scale (ESS)	Consists of eight scenarios of daily activity, and participants use a four-point Likert scale to rate how likely they are to doze. Score ranges 0-24 with a higher score indicating daytime sleepiness.	baseline, Week 6, Month 6
Dysfunctional Beliefs About Sleep	This assessment is a 10 item Likert-scale self-report questionnaire. Higher scores indicate more dysfunctional beliefs.	baseline, Week 6, Month 6
Positive Affect and Negative Affect Schedule (PANAS)	is a 20-item self-report questionnaire used to measure positive and negative emotions. There are two subscales (Positive Affect and Negative Affect) with 10 items each. The respondent scores how applicable a list of emotions are on a 5-point Likert scale with 1 = "Very slightly or not at all" to 5 = "Extremely". A higher score on the Positive Affect subscale indicates greater intensity of positive emotions, and a high score on Negative Affect indicate greater intensity of negative emotions.	baseline, Week 6, Month 6
Sleep Self-Efficacy Scale (SESS)	Sleep Self-Efficacy is a 9 item self-report Likert-scale questionnaire use to identify sleep self-efficacy. Scores range from 0-45 and a higher score indicates higher sleep self-efficacy.	baseline, Week 6, Month 6
Actigraphy	Participants will wear an actigraph on their non-dominant wrist for 7 nights to assess sleep/wake cycle. Mains variables of interest are sleep regularity, timing, efficiency, and duration	baseline, Week 6, Month 6
Modified Fatigue Impact Scale (MFIS)	The MFIS assesses the impact of fatigue on daily activities for the month prior. The MFIS consists of 21 items with 3 subscales: physical, cognitive, and psychosocial. The score on the 21 items are scored with a range of 0-84 with a higher score indicating a greater impact of fatigue.	baseline, Week 6, Month 6
Fatigue Severity Scale (FSS)	The FSS assesses the impact of fatigue on activities for the week prior and consists of 9 questions. The mean of the 9 scores is calculated with a range of 0-7.	baseline, Week 6, Month 6
Multiple Sclerosis Impact Scale (MSIS-29)	Quality of life will be assessed using the Multiple Sclerosis Impact Scale (MSIS-29). MSIS-29 is total of 29 items scale, with subscales of physical (20 items) and psychological (9 items). Responses computed in a range from 0-100, and higher scores indicating a worse quality of life due to physical and physiological impacts of MS	baseline, Week 6, Month 6
Cognitive Failures Questionnaire (CFQ)	Cognitive Failures Questionnaire (CFQ) assesses perception of cognitive abilities over the past 6 months. consists of 25 items that the individual rates on a 5-point Likert scale with 0 = "never" and 4 = "Very Often" with a summary score of 0-100 with a higher score indicating poorer perceived cognitive abilities.	baseline, Week 6, Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Determined Disability Steps (PDDS)	Disability will be assessed using the PDDS scale which is a single-item 9 point scale ranging from "normal" (score of 0) to "bedridden" (score of 8).	baseline
Patient Health Questionnaire (PHQ-9)	Depressive symptoms will be assessed using the 9-item Patient Health Questionnaire (PHQ-9), with a score of ≥20 suggesting severe depression. It consists of 9 items with a score ranging from 0-27.	baseline, Week 6, Month 6
Generalized Anxiety Disorder Assessment (GAD-7)	Anxiety symptoms will be assessed using the 7-item GAD-7, with a score of ≥15 indicating severe anxiety. This questionnaire consists of 7 items, and the score from each item is summed for an overall score ranging from 0-21 with a higher score indicating a higher level of anxiety	baseline, Week 6, Month 6
Adherence to CBT-I intervention	To assess adherence to the CBT-I intervention, the sleep log will be used to assess number of mornings/week got out of bed at agreed upon time and the number of times got out of bed if unable to sleep. A total percentage will be calculated and used as the outcome of interest.	Each CBT-I session Week 1-6
Diet quality	Participants will be asked "In general, how healthy is your overall diet?" and will rate on a 5-point Likert scale (5 = "excellent", 4 = "very good", 3 = "good", 2 = "fair", 1 = "poor")	baseline
Eating regularity	Participants will mark on the sleep log at each assessment period the time period for eating breakfast, lunch, and dinner. Variability in mealtime will be quantified as the standard deviation from the individual's mean meal start time.	baseline, Week 6, Month 6
Nighttime urination frequency	Participants will mark on the sleep log the number of times they wake up to void their bladder during the sleep opportunity window.	baseline, Week 6, Month 6
PainDetect	PainDetect includes 13 items that assesses neuropathic pain. A total score ranges from -1 to 38, with higher scores indicating higher levels of neuropathic pain.	baseline, Week 6, Month 6
Fibromyalgia Survey Questionnaire	Fibromyalgia Survey Questionnaire includes the assessment of the number of painful body regions. Scores ranges from 0-31. A higher score indicates worse symptoms.	baseline, Week 6, Month 6
PROMIS SF v.1.0 - Pain Intensity	Measures max and average pain intensity during past 7 days. The T-score value, with a mean of 50 and standard deviation of 10 representing the rescaled raw score, will be reported.	baseline, Week 6, Month 6

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 22, 2024
• First Posted (Actual): May 24, 2024

Study Record Updates

• Last Update Posted (Actual): July 20, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: CBT-I; Cognitive behavioral therapy for insomnia
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Multiple Sclerosis; Sclerosis; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: STUDY00160476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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