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

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

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).

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

Study Overview

• Status: Completed
• Conditions: Insomnia; End Stage Renal Disease
• Intervention / Treatment: Behavioral: Cognitive Behavioral Therapy for Insomnia; Drug: Trazodone; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98122
      • Northwest Kidney Centers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: CBT-I
Active Comparator: Medication- Trazodone; Trazodone (50-100 mg):	Drug: Trazodone; trazodone tablet; Other Names: Desyrel
Placebo Comparator: Medication- Placebo; Placebo (for trazodone)	Drug: Placebo; Inactive pill manufactured to mimic trazodone tablets.; Other Names: Placebo (for trazodone)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insomnia Severity Index (ISI) Short-term	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	Week 7
Insomnia Severity Index (ISI) Long-term	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	Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported Outcomes (PRO) - Pittsburgh Sleep Quality Index - Short-term	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	Week 7
Patient-reported Outcomes (PRO) - Pittsburgh Sleep Quality Index - Long-term	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	Week 25
Patient-reported Outcomes (PRO) - Epworth Sleepiness Scale - Short-term	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	Week 7
Patient-reported Outcomes (PRO) - Epworth Sleepiness Scale - Long-term	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	Week 25
Patient-reported Outcomes (PRO) - FACIT Fatigue Scale- Short-term	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	Week 7
Patient-reported Outcomes (PRO) - FACIT Fatigue Scale- Long-term	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	Week 25
Patient-reported Outcomes (PRO) - Patient Health Questionnaire 9 - Short-term	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	Week 7
Patient-reported Outcomes (PRO) - Patient Health Questionnaire 9 - Long-term	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	Week 25
Patient-reported Outcomes (PRO) - Generalized Anxiety Disorder 7 Scale - Short-term	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	Week 7
Patient-reported Outcomes (PRO) - Generalized Anxiety Disorder 7 Scale - Long-term	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	Week 25
Objective Measure of Sleep - Long-term	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	Week 25
Patient-reported Outcomes (PRO) - Graded Chronic Pain Scale - Short-term	Score from first 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	Week 7
Patient-reported Outcomes (PRO) - Graded Chronic Pain Scale - Long-term	Score from first 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	Week 25
Patient-reported Outcomes (PRO) - Graded Chronic Pain Scale - Interference - Short-term	Score from Second Item Graded Chronic Pain scale, measuring pain interference, range 0 to 10. Higher scores indicates greater interference from pain: at Week 7 describing the short-term effect of the intervention	Week 7
Patient-reported Outcomes (PRO) - Graded Chronic Pain Scale - Interference - Long-term	Score from Second Item Graded Chronic Pain scale, measuring pain interference, range 0 to 10. Higher scores indicates greater interference from pain: at Week 25 describing the long-term effect of the intervention	Week 25
Patient-reported Outcomes (PRO) - Quality of Life Short Form 12 Scale - Physical Component Score - Short-term	Score from Quality of Life Short Form 12 scale - Physical Component Score, 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	Week 7
Patient-reported Outcomes (PRO) - Quality of Life Short Form 12 Scale - Physical Component Score - Long-term	Score from Quality of Life Short Form 12 scale - Physical Component Score, 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	Week 25
Patient-reported Outcomes (PRO) - Quality of Life Short Form 12 Scale - Mental Component Score - Short-term	Score from Quality of Life Short Form 12 scale - Mental Component Score, 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	Week 7
Patient-reported Outcomes (PRO) - Quality of Life Short Form 12 Scale - Mental Component Score - Long-term	Score from Quality of Life Short Form 12 scale - Mental Component Score, 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	Week 25
Cumulative Weekly Use of Sedatives/Hypnotics - Short-term	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	Week 7
Cumulative Weekly Use of Sedatives/Hypnotics - Long-term	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	Week 25
Objective Measure of Sleep - Short-term	Actigraphy measurement of average nighttime sleep efficiency (percent time asleep of time in bed): at Week 7 describing the short-term effect of the intervention	Week 7

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Raj Mehrotra, MD, University of Washington

Publications and helpful links

General Publications

• Unruh M, Cukor D, Rue T, Abad K, Roumelioti ME, McCurry SM, Heagerty P, Mehrotra R. Sleep-HD trial: short and long-term effectiveness of existing insomnia therapies for patients undergoing hemodialysis. BMC Nephrol. 2020 Oct 20;21(1):443. doi: 10.1186/s12882-020-02107-x.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2018
• Primary Completion (Actual): October 17, 2022
• Study Completion (Actual): November 17, 2022

Study Registration Dates

• First Submitted: May 1, 2018
• First Submitted That Met QC Criteria: May 11, 2018
• First Posted (Actual): May 23, 2018

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Cognitive behavioral therapy; Hemodialysis; Kidney disease; Trazodone
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sleep Initiation and Maintenance Disorders; Kidney Failure, Chronic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Selective Serotonin Reuptake Inhibitors; Trazodone
• Other Study ID Numbers: STUDY00004678 (Other Identifier: Emory University Hospital/Winship Cancer Institute); R01DK115468 (U.S. NIH Grant/Contract)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No