DIalysis Symptom COntrol-Pruritus Outcome Trial (DISCO-POT)

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

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.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; Pruritus
• Intervention / Treatment: Drug: Nabilone 0.5 MG Oral Capsule; Drug: Placebo Nabilone

Detailed Description

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:

1. nabilone 0.5 mg orally at night for 1 week increased to nabilone 0.5mg orally twice a day for 3 weeks (over-encapsulated)
2. placebo 1 capsule orally at night for 1 week increased to placebo 2 capsules twice a day for 3 weeks (over-encapsulated)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2P4
      • University of Alberta Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2V 3M3
      • Seven Oaks General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age>25 years
2. In-center or home hemodialysis at least two times weekly or peritoneal dialysis at least once daily for >90 days
3. Generalized uremic pruritus with a mean worst VAS>40mm over the previous week (with at least 5/7 patient diary days completed)
4. 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
5. Able to provide informed consent and complete patient reported outcome measurements without a language barrier or cognitive impairment

Exclusion Criteria:

1. Etiology of pruritus (in the opinion of the treating physician) thought to be secondary to primary dermatologic condition, liver disease, hematologic malignancy or allergy
2. Use of recreational or medical cannabis in the last 4 weeks (THC, CBD, nabilone, Sativex, Epidiolex)
3. Women of childbearing potential as assessed by their clinician regardless of abstinence from sex or the use of contraception
4. Planned kidney transplantation, travel or relocation in the next 3 months
5. Unstable psychiatric illness (the presence of a lifetime diagnosis of a psychotic disorder, bipolar disorder, substance use disorder or current suicidal ideation)
6. 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)
7. History of hypersensitivity to any cannabinoid
8. Presence of any clinically significant or unstable medical conditions, including cardiovascular, liver, pulmonary disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nabilone 0.5mg; 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; 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.; Other Names: TEVA-Nabilone
Placebo Comparator: Oral placebo; 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; 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.; Other Names: TEVA-Nabilone Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Population Health Research Institute
• Investigators: Principal Investigator: David Collister, MD, PhD, University of Manitoba

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Actual): August 11, 2023
• Study Completion (Actual): August 11, 2023

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: December 18, 2021
• First Posted (Actual): January 6, 2022

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; Itch; Dialysis; Pruritis; Nabilone; Uremic
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Skin Manifestations; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Pruritus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antiemetics; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol; Nabilone
• Other Study ID Numbers: B2021:096

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: No
• Studies a U.S. FDA-regulated device product: No