Short and Long-Term Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis

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

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.

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

Conditions
-----------------
Insomnia, End Stage Renal Disease

Intervention / Treatment
-----------------
* Behavioral: Cognitive Behavioral Therapy for Insomnia
* Drug: Trazodone
* Drug: Placebo


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CBT-I<br>Cognitive Behavioral Therapy for Insomnia sessions: a 30-minute treatment session once weekly for six weeks. | Behavioral: Cognitive Behavioral Therapy for Insomnia<br>* 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.<br>* Other names: CBT-I;|
| Active Comparator: Medication- Trazodone<br>Trazodone (50-100 mg): | Drug: Trazodone<br>* trazodone tablet<br>* Other names: Desyrel;|
| Placebo Comparator: Medication- Placebo<br>Placebo (for trazodone) | Drug: Placebo<br>* Inactive pill manufactured to mimic trazodone tablets.<br>* 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) - Two-Item Graded Chronic Pain scale - Short-term | 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 | Week 7 | 
| Patient-reported Outcomes (PRO) - Two-Item Graded Chronic Pain scale - Long-term | 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 | 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 | 
| Patient-reported Outcomes (PRO) - Quality of Life Short Form 12 scale - Short-term | 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 | Week 7 | 
| Patient-reported Outcomes (PRO) - Quality of Life Short Form 12 scale - Long-term | 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 | 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 6 describing the short-term effect of the intervention | Week 6 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hemodialysis, Kidney disease, Trazodone, Cognitive behavioral therapy