## Protocol Section
### Identification Module
**NCT ID:** NCT06428006

**Acronym:** CALM

**Brief Title:** Efficacy of Cognitive Behavioral Therapy for Insomnia to Treat Insomnia Symptoms in Individuals With Multiple Sclerosis

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

#### Organization Study ID Info
**ID:** STUDY00160476
#### Organization
**Class:** OTHER
**Full Name:** University of Kansas Medical Center
### Status Module
#### Completion Date
**Date:** 2027-05-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-22

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-05-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Kansas Medical Center

#### Responsible Party

**Investigator Affiliation:** University of Kansas Medical Center

**Investigator Full Name:** Catherine Siengsukon, PT, PhD

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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).

### Conditions Module

**Conditions:**

- Multiple Sclerosis

- Insomnia

**Keywords:**

- Cognitive behavioral therapy for insomnia

- CBT-I

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 70

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Behavioral: Cognitive behavioral therapy for insomnia

**Label:** Cognitive behavioral therapy for insomnia

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Behavioral: Sleep and lifestyle education

**Label:** Sleep and lifestyle education

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cognitive behavioral therapy for insomnia

**Description:** 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

**Name:** Cognitive behavioral therapy for insomnia

**Type:** BEHAVIORAL

#### Intervention 2

**Arm Group Labels:**

- Sleep and lifestyle education

**Description:** 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

**Name:** Sleep and lifestyle education

**Type:** BEHAVIORAL

### Outcomes Module

#### Other Outcomes

**Description:** 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).

**Measure:** Patient-Determined Disability Steps (PDDS)

**Time Frame:** baseline

**Description:** 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.

**Measure:** Patient Health Questionnaire (PHQ-9)

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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

**Measure:** Generalized Anxiety Disorder Assessment (GAD-7)

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** Adherence to CBT-I intervention

**Time Frame:** Each CBT-I session Week 1-6

**Description:** 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")

**Measure:** Diet quality

**Time Frame:** baseline

**Description:** 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.

**Measure:** Eating regularity

**Time Frame:** baseline, Week 6, Month 6

**Description:** Participants will mark on the sleep log the number of times they wake up to void their bladder during the sleep opportunity window.

**Measure:** Nighttime urination frequency

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** PainDetect

**Time Frame:** baseline, Week 6, Month 6

**Description:** Fibromyalgia Survey Questionnaire includes the assessment of the number of painful body regions. Scores ranges from 0-31. A higher score indicates worse symptoms.

**Measure:** Fibromyalgia Survey Questionnaire

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** PROMIS SF v.1.0 - Pain Intensity

**Time Frame:** baseline, Week 6, Month 6

#### Primary Outcomes

**Description:** 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.

**Measure:** Insomnia Severity Index (ISI)

**Time Frame:** baseline, Week 6, Month 6

#### Secondary Outcomes

**Description:** 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.

**Measure:** Pittsburgh Sleep Quality Index (PSQI)

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** Epworth Sleepiness Scale (ESS)

**Time Frame:** baseline, Week 6, Month 6

**Description:** This assessment is a 10 item Likert-scale self-report questionnaire. Higher scores indicate more dysfunctional beliefs.

**Measure:** Dysfunctional Beliefs About Sleep

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** Positive Affect and Negative Affect Schedule (PANAS)

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** Sleep Self-Efficacy Scale (SESS)

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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

**Measure:** Actigraphy

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** Modified Fatigue Impact Scale (MFIS)

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** Fatigue Severity Scale (FSS)

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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

**Measure:** Multiple Sclerosis Impact Scale (MSIS-29)

**Time Frame:** baseline, Week 6, Month 6

**Description:** 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.

**Measure:** Cognitive Failures Questionnaire (CFQ)

**Time Frame:** baseline, Week 6, Month 6

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** enelson5@kumc.edu

**Name:** Eryen Nelson, MPH

**Phone:** 913-945-7349

**Role:** CONTACT

**Contact 2:**

**Email:** csiengsukon@kumc.edu

**Name:** Catherine Siengsukon, PhD

**Phone:** 913-588-6913

**Role:** CONTACT

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000020278

- Term: Demyelinating Autoimmune Diseases, CNS

- ID: D000020274

- Term: Autoimmune Diseases of the Nervous System

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000003711

- Term: Demyelinating Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000007154

- Term: Immune System Diseases

- ID: D000020919

- Term: Sleep Disorders, Intrinsic

- ID: D000020920

- Term: Dyssomnias

- ID: D000012893

- Term: Sleep Wake Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

### Condition Browse Module - Browse Leaves

- ID: M8364

- Name: Fatigue

- Relevance: LOW

- As Found: Unknown

- ID: M15415

- Name: Sclerosis

- Relevance: HIGH

- As Found: Sclerosis

- ID: M12060

- Name: Multiple Sclerosis

- Relevance: HIGH

- As Found: Multiple Sclerosis

- ID: M10356

- Name: Sleep Initiation and Maintenance Disorders

- Relevance: HIGH

- As Found: Insomnia

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22098

- Name: Demyelinating Autoimmune Diseases, CNS

- Relevance: LOW

- As Found: Unknown

- ID: M22094

- Name: Autoimmune Diseases of the Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M6909

- Name: Demyelinating Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22242

- Name: Parasomnias

- Relevance: LOW

- As Found: Unknown

- ID: M22654

- Name: Sleep Disorders, Intrinsic

- Relevance: LOW

- As Found: Unknown

- ID: M22655

- Name: Dyssomnias

- Relevance: LOW

- As Found: Unknown

- ID: M15696

- Name: Sleep Wake Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009103

- Term: Multiple Sclerosis

- ID: D000007319

- Term: Sleep Initiation and Maintenance Disorders

- ID: D000012598

- Term: Sclerosis

### Intervention Browse Module - Browse Branches

- Abbrev: CNSSti

- Name: Central Nervous System Stimulants

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M5373

- Name: Caffeine

- Relevance: LOW

- As Found: Unknown

- ID: T370

- Name: Caffeine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
