DIalysis Symptom COntrol-Pruritus Outcome Trial

Study Overview
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Brief Summary
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The purpose of this study is to test whether or not a medication called nabilone, which is a synthetic (non-natural) medication derived from cannabis, compared to placebo improves symptoms of itch in hemodialysis as measured by visual analog scales.

Detailed Description
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Several different types of medications are effective in treating uremic pruritus, but even with effective treatments, residual symptoms are common and some medications are not well tolerated. Standard of care treatments include emollients which are lotions that keep the skin hydrated and a variety of pills that target the itch pathways implicated in the disease. The objective of the study is to determine the proportion of patients with kidney failure for whom oral nabilone provides important benefit in reducing uremic pruritis without important adverse effects. The hypothesis is that there is a substantial proportion of patients in whom oral nabilone are safe and effective beyond placebo effects. Nabilone is currently used to treat conditions other that uremic pruritus including chronic nerve pain as well as nausea and vomiting due to chemotherapy. It has never been studied in the setting of kidney disease. DISCO-POT is a blinded, placebo-controlled crossover trial in which participants will be followed for 11 weeks including two 4 week treatment crossover periods with a 2 week washout period in between them and an end of study visit after 1 week off study drugs. Patients that are eligible will be randomly assigned to a crossover treatment sequence of two treatments: nabilone 0.5 mg orally at night for 1 week increased to nabilone 0.5mg orally twice a day for 3 weeks (over-encapsulated) placebo 1 capsule orally at night for 1 week increased to placebo 2 capsules twice a day for 3 weeks (over-encapsulated)

Official Title
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Dialysis Symptom Control-Pruritus Outcome Trial: A Randomized Blinded Placebo Controlled Crossover Trial

Conditions
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End Stage Renal Disease, Pruritus

Intervention / Treatment
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* Drug: Nabilone 0.5 MG Oral Capsule
* Drug: Placebo Nabilone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age>25 years In-center or home hemodialysis at least two times weekly or peritoneal dialysis at least once daily for >90 days Generalized uremic pruritus with a mean worst VAS>40mm over the previous week (with at least 5/7 patient diary days completed) ALT less or equal to 3x upper limit of normal and bilirubin less than or equal to 2x upper limit of normal in the last 90 days Able to provide informed consent and complete patient reported outcome measurements without a language barrier or cognitive impairment Exclusion Criteria: Etiology of pruritus (in the opinion of the treating physician) thought to be secondary to primary dermatologic condition, liver disease, hematologic malignancy or allergy Use of recreational or medical cannabis in the last 4 weeks (THC, CBD, nabilone, Sativex, Epidiolex) Women of childbearing potential as assessed by their clinician regardless of abstinence from sex or the use of contraception Planned kidney transplantation, travel or relocation in the next 3 months Unstable psychiatric illness (the presence of a lifetime diagnosis of a psychotic disorder, bipolar disorder, substance use disorder or current suicidal ideation) Symptomatic hypotension in the last 2 weeks defined as a systolic blood pressure (SBP) less than 90mmHg during or in between dialysis requiring an intervention (i.e. administration of crystalloid or colloid, termination of dialysis, change in pharmacologic therapy such as withdrawal of anti-hypertensive therapy or initiation/titration of midodrine, increase in dry weight) History of hypersensitivity to any cannabinoid Presence of any clinically significant or unstable medical conditions, including cardiovascular, liver, pulmonary disease

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nabilone 0.5mg<br>Subjects will receive nabilone 0.5 mg orally at night for 1 week increased to nabilone 0.5mg orally twice a day for 3 weeks (over-encapsulated). Drug will be dispensed from a central site to other sites and pharmacy personnel will dispense the study medications directly to research personnel or participants. Drug dispensation will coincide with study visits at randomization and crossover and will allow research personnel to reinforced adherence. The study oral medications may be taken at any time of day with food or water, but we will request that participants take it at the same time each day, preferably at night when uremic pruritus symptoms are usually at the worst. If participants have any side effects or intolerability to study drugs, they may decrease the frequency of nabilone or placebo to 1 capsule by mouth once daily, preferably taken at night. | Drug: Nabilone 0.5 MG Oral Capsule<br>* This intervention will consist of subjects receiving nabilone 0.5 mg orally at night for 1 week increased to nabilone 0.5mg orally twice a day for 3 weeks. Duration of the intervention will be 4 weeks.<br>* Other names: TEVA-Nabilone;|
| Placebo Comparator: Oral placebo<br>Subjects will receive placebo 1 capsule orally at night for 1 week increased to placebo 2 capsules twice a day for 3 weeks (over-encapsulated). Drug will be dispensed from a central site to other sites and pharmacy personnel will dispense the study medications directly to research personnel or participants. Drug dispensation will coincide with study visits at randomization and crossover and will allow research personnel to reinforced adherence. The study oral medications may be taken at any time of day with food or water, but we will request that participants take it at the same time each day, preferably at night when uremic pruritus symptoms are usually at the worst. If participants have any side effects or intolerability to study drugs, they may decrease the frequency of nabilone or placebo to 1 capsule by mouth once daily, preferably taken at night. | Drug: Placebo Nabilone<br>* This intervention will consist of subjects receiving placebo 1 capsule orally at night for 1 week increased to placebo 2 capsules twice a day for 3 weeks. Duration of the intervention will be 4 weeks.<br>* Other names: TEVA-Nabilone Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in worst uremic pruritis severity rating between treatment arms relative to MID | Measured using Visual Analogue Scale (VAS) | Measured at study baseline and weeks 1,2,3,4,5,6,7,8,9,10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with safety outcomes including adverse events related to study drug | serious adverse events, adverse events leading to drug discontinuation, hospitalization or emergency room visit for altered level of consciousness, fall, fracture, death, symptomatic hypotension requiring an intervention | Measured at study baseline and weeks 1,2,3,4,5,6,7,8,9,10,11 | 
| Change in uremic pruritis severity | Measured as change from baseline in mean Visual Analogue Scale (VAS) | Measured at study baseline and weeks 1,2,3,4,5,6,7,8,9,10 | 
| Change in uremic pruritis severity | Measured as change from baseline in mean Verbal Rating Scale (VRS) | Measured at study baseline and weeks 1,2,3,4,5,6,7,8,9,10 | 
| Change in health-related quality of life | Measured using the Dermatology Quality of Life Index (DLQI) | Measured at study baseline and weeks 3 and 4 of each crossover | 
| Change in health-related quality of life | Measured using the EQ-5D 5 Level (EQ-5D-5L) | Measured at study baseline and weeks 3 and 4 of each crossover | 
| Change in health-related quality of life | Measured using the Patient Global Impression (PGI) | Measured at study baseline and weeks 3 and 4 of each crossover | 
| Effect of nabilone on sleep quality | Measured using the Pittsburgh Sleep Quality Index (PSQI) | Measured at study baseline and weeks 3 and 4 of each crossover | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uremic, Pruritis, Itch, End Stage Renal Disease, Dialysis, Nabilone