Short and Long-Term Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis (Sleep-HD)

• ClinicalTrials.gov Identifier: NCT03534284
• Recruitment Status: Recruiting
• First Posted: May 23, 2018
• Last Update Posted: October 18, 2018
• Sponsor: University of Washington
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Rajnish Mehrotra, University of Washington

Study Description

Brief Summary:

Insomnia is a common and distressing symptom for patients on hemodialysis (HD), and there is evidence for a much larger impact on the health of patients. Chronic insomnia is disrupted sleep that occurs at least three nights per week and lasts at least three months.

The SLEEP-HD study is a randomized open-label clinical trial to compare two types of treatment for insomnia in participants who have end-stage renal disease on HD, and who have been diagnosed with chronic insomnia. The two types of treatment involved in the study are Cognitive Behavioral Therapy for Insomnia (CBT-I) or treatment with a drug (trazodone vs placebo).

125 participants will be enrolled who are undergoing HD in two study locations (Seattle, Washington and Albuquerque, New Mexico).

Condition or disease	Intervention/treatment	Phase
Insomnia; End Stage Renal Disease	Behavioral: Cognitive Behavioral Therapy for Insomnia; Drug: Trazodone; Drug: Placebo	Phase 3

Detailed Description:

Most HD patients have significant impairments in quality of life, largely from the high frequency of disabling symptoms. Insomnia is one of the most frequently reported symptoms and studies of HD patients and/or other populations suggest that it is a significant contributor to other common symptoms and poor health outcomes. There are unique contributors to chronic insomnia in HD patients and these include the biologic effects of residual uremia after partial correction as is achieved with current dialysis technology, maladaptation to treatment schedules, and patients' napping during treatments.

There is a compelling need to identify effective treatments for insomnia in HD patients and the interventions being studied in this clinical trial, telehealth cognitive behavioral therapy for insomnia (CBT-I) and trazodone, have a strong scientific premise. If telehealth (web-based) CBT-I is effective for insomnia in HD patients, it will make a treatment that is presently inaccessible available to patients. Trazodone is widely used but the data on efficacy for insomnia are limited; no such data exist for HD patients.

SLEEP-HD is a parallel group randomized controlled trial wherein 125 HD patients with chronic insomnia, treated in community-based dialysis facilities in Seattle and Albuquerque, will be randomized 1:1:1 over 31 months to 6-week treatment with telehealth CBT-I, trazodone, or medication placebo.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: SLEEP-HD is a parallel group randomized controlled trial wherein 125 HD patients with chronic insomnia, treated in community-based dialysis facilities in Seattle and Albuquerque, will be randomized 1:1:1 over 31 months to 6-week treatment with telehealth CBT-I, trazodone, or medication placebo.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: The investigator, the participant, and the care provider will be blinded to the drug assignment (trazodone vs. placebo) for those subjects randomized into the medication intervention arm.
• Primary Purpose: Treatment
• Official Title: Short and Long-Term Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis (Sleep-HD)
• Actual Study Start Date: September 19, 2018
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: August 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: CBT-I; Cognitive Behavioral Therapy for Insomnia sessions: a 30-minute treatment session once weekly for six weeks.	Behavioral: Cognitive Behavioral Therapy for Insomnia; Once weekly treatment sessions for 6 weeks. The content of each of these sessions will be adapted to include changes in behavior during HD treatments (such as napping) and to help patients better adjust to treatment schedules. The CBT-I sessions will be delivered by a therapist face-to-face with the patient via a fully interactive video telehealth platform.; Other Name: CBT-I
Active Comparator: Medication- Trazodone; Trazodone (50-100 mg):	Drug: Trazodone; trazodone tablet; Other Name: Desyrel
Placebo Comparator: Medication- Placebo; Placebo (for trazodone)	Drug: Placebo; Inactive pill manufactured to mimic trazodone tablets.; Other Name: Placebo (for trazodone)

Outcome Measures

Primary Outcome Measures :

1. Insomnia Severity Index (ISI) Short-term [ Time Frame: Week 7 ]
   summary score obtained from the ISI, measuring insomnia, range from 0 to 28. Higher score indicates greater insomnia, at Week 7 describing the short-term effect of the intervention
2. Insomnia Severity Index (ISI) Long-term [ Time Frame: Week 25 ]
   summary score obtained from the ISI, measuring insomnia, range from 0 to 28. Higher score indicates greater insomnia, at Week 25 describing the long-term effect of the intervention

Secondary Outcome Measures :

1. Patient-reported Outcomes (PRO) - Pittsburgh Sleep Quality Index - Short-term [ Time Frame: Week 7 ]
   Score from Pittsburgh Sleep Quality Index, measuring sleep quality, range 0 to 21. Higher scores indicates worse sleep quality: at Week 7 describing the short-term effect of the intervention
2. Patient-reported Outcomes (PRO) - Pittsburgh Sleep Quality Index - Long-term [ Time Frame: Week 25 ]
   Score from Pittsburgh Sleep Quality Index, measuring sleep quality, range 0 to 21. Higher scores indicates worse sleep quality: at Week 25 describing the long-term effect of the intervention
3. Patient-reported Outcomes (PRO) - Epworth Sleepiness Scale - Short-term [ Time Frame: Week 7 ]
   Score from Epworth Sleepiness Scale, measuring sleepiness, range 0 to 24. Higher scores indicates greater sleepiness: at Week 7 describing the short-term effect of the intervention
4. Patient-reported Outcomes (PRO) - Epworth Sleepiness Scale - Long-term [ Time Frame: Week 25 ]
   Score from Epworth Sleepiness Scale, measuring sleepiness, range 0 to 24. Higher scores indicates greater sleepiness: at Week 25 describing the long-term effect of the intervention
5. Patient-reported Outcomes (PRO) - FACIT Fatigue Scale- Short-term [ Time Frame: Week 7 ]
   Score from FACIT Fatigue Scale, measuring fatigue, range 0 to 52. Higher scores indicates greater fatigue: at Week 7 describing the short-term effect of the intervention
6. Patient-reported Outcomes (PRO) - FACIT Fatigue Scale- Long-term [ Time Frame: Week 25 ]
   Score from FACIT Fatigue Scale, measuring fatigue, range 0 to 52. Higher scores indicates greater fatigue: at Week 25 describing the long-term effect of the intervention
7. Patient-reported Outcomes (PRO) - Two-Item Graded Chronic Pain scale - Short-term [ Time Frame: Week 7 ]
   Score from Two-Item Graded Chronic Pain scale, measuring pain, range 0 to 10. Higher scores indicates greater pain: at Week 7 describing the short-term effect of the intervention
8. Patient-reported Outcomes (PRO) - Two-Item Graded Chronic Pain scale - Long-term [ Time Frame: Week 25 ]
   Score from Two-Item Graded Chronic Pain scale, measuring pain, range 0 to 10. Higher scores indicates greater pain: at Week 25 describing the long-term effect of the intervention
9. Patient-reported Outcomes (PRO) - Patient Health Questionnaire 9 - Short-term [ Time Frame: Week 7 ]
   Score from Patient Health Questionnaire 9, measuring depression, range 0 to 27. Higher scores indicates greater depression: at Week 7 describing the short-term effect of the intervention
10. Patient-reported Outcomes (PRO) - Patient Health Questionnaire 9 - Long-term [ Time Frame: Week 25 ]
    Score from Patient Health Questionnaire 9, measuring depression, range 0 to 27. Higher scores indicates greater depression: at Week 25 describing the long-term effect of the intervention
11. Patient-reported Outcomes (PRO) - Generalized Anxiety Disorder 7 Scale - Short-term [ Time Frame: Week 7 ]
    Score from Generalized Anxiety Disorder 7 Scale, measuring anxiety, range 0 to 21. Higher scores indicates greater anxiety: at Week 7 describing the short-term effect of the intervention
12. Patient-reported Outcomes (PRO) - Generalized Anxiety Disorder 7 Scale - Long-term [ Time Frame: Week 25 ]
    Score from Generalized Anxiety Disorder 7 Scale, measuring anxiety, range 0 to 21. Higher scores indicates greater anxiety: at Week 25 describing the long-term effect of the intervention
13. Patient-reported Outcomes (PRO) - Quality of Life Short Form 12 scale - Short-term [ Time Frame: Week 7 ]
    Score from Quality of Life Short Form 12 scale, measuring quality of life, range 0 to 100. Higher scores indicates better quality of life: at Week 7 describing the short-term effect of the intervention
14. Patient-reported Outcomes (PRO) - Quality of Life Short Form 12 scale - Long-term [ Time Frame: Week 25 ]
    Score from Quality of Life Short Form 12 scale, measuring quality of life, range 0 to 100. Higher scores indicates better quality of life: at Week 25 describing the long-term effect of the intervention
15. Cumulative Weekly use of Sedatives/Hypnotics - Short-term [ Time Frame: Week 7 ]
    This will be defined, as the number of days that the patient took a drug to help sleep, range from 0 to 7: at Week 7 describing the short-term effect of the intervention
16. Cumulative Weekly use of Sedatives/Hypnotics - Long-term [ Time Frame: Week 25 ]
    This will be defined, as the number of days that the patient took a drug to help sleep, range from 0 to 7: at Week 25 describing the long-term effect of the intervention
17. Objective Measure of Sleep - Short-term [ Time Frame: Week 6 ]
    Actigraphy measurement of average nighttime sleep efficiency (percent time asleep of time in bed): at Week 6 describing the short-term effect of the intervention
18. Objective Measure of Sleep - Long-term [ Time Frame: Week 25 ]
    Actigraphy measurement of average nighttime sleep efficiency (percent time asleep of time in bed): at Week 25 describing the long-term effect of the intervention

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Undergoing thrice-weekly maintenance hemodialysis for ≥ 3 months
• Able to speak English
• ISI score ≥ 10 at pre-screening with sleep disturbances for ≥ 3 nights per week for ≥ 3 months

Exclusion Criteria:

• Severe cognitive impairment on Mini-COG cognitive test (score < 3)
• Severe depression assessed by Patient Health Questionnaire (PHQ)-2 and if appropriate, PHQ-9
• Suicidal Ideation
• Alcohol abuse on CAGE alcohol assessment questionnaire (score ≥ 2) or substance abuse on Drug Abuse Screening Test (DAST)-10 questionnaire (score > 5)
• Severe restless leg syndrome
• Treatment with trazodone in the past one month
• Known allergy to trazodone (self-report or by chart review)
• Current treatment with monoamine oxidase inhibitors or in the preceding 14 days
• Current treatment with linezolid (self-report or by chart review)
• Current treatment with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), antipsychotic medications (ziprasidone, chlorpromazine, thioridazine), and quinolone antibiotics
• Pregnancy, or lactation, or women of childbearing potential not willing to use adequate birth control
• Life Expectancy < 3 months
• Expected to receive a kidney transplant or transition to home dialysis (peritoneal dialysis or home hemodialysis) within 6 months
• Any other condition that, in the opinion of the investigator, should preclude patient participation in the clinical trial

Contacts and Locations

Contacts

Contact: Lori Linke; 206-720-3835; llinke@nephrology.washington.edu

Contact: Carlyn Clark, MSW; 206-720-8811; cclark@nephrology.washington.edu

Locations

United States, Washington

Northwest Kidney Centers; Recruiting

Seattle, Washington, United States, 98122

Contact: Lori Linke, BA 206-720-3835 llinke@nephrology.washington.edu

Contact: Carlyn Clark, MSW 206-720-8811 cclark@nephrology.washington.edu

Sponsors and Collaborators

University of Washington

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Raj Mehrotra, MD; University of Washington

More Information

• Responsible Party: Rajnish Mehrotra, Section Head Nephrology, School of Medicine: Department of Medicine, University of Washington
• ClinicalTrials.gov Identifier: NCT03534284
• Other Study ID Numbers: STUDY00004678; R01DK115468 ( U.S. NIH Grant/Contract )
• First Posted: May 23, 2018
• Last Update Posted: October 18, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rajnish Mehrotra, University of Washington:

Hemodialysis; Kidney disease; Trazodone; Cognitive behavioral therapy

Additional relevant MeSH terms:

Sleep Initiation and Maintenance Disorders; Kidney Failure, Chronic; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Trazodone; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents