Clinical trial NCT05180968: DIalysis Symptom COntrol-Pruritus Outcome Trial
Official title: Dialysis Symptom Control-Pruritus Outcome Trial: A Randomized Blinded Placebo Controlled Crossover Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: End Stage Renal Disease
Pruritus
Keywords: Uremic
Pruritis
Itch
End Stage Renal Disease
Dialysis
Nabilone
Lead sponsor: University of Manitoba
Sponsor class: OTHER
Collaborators: name: Population Health Research Institute
First posted: 2022-01-06
Enrollment: 14
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in worst uremic pruritis severity rating between treatment arms relative to MID
timeFrame: Measured at study baseline and weeks 1,2,3,4,5,6,7,8,9,10
Secondary outcomes:
measure: Number of participants with safety outcomes including adverse events related to study drug
timeFrame: Measured at study baseline and weeks 1,2,3,4,5,6,7,8,9,10,11
measure: Change in uremic pruritis severity
timeFrame: Measured at study baseline and weeks 1,2,3,4,5,6,7,8,9,10
measure: Change in uremic pruritis severity
timeFrame: Measured at study baseline and weeks 1,2,3,4,5,6,7,8,9,10
measure: Change in health-related quality of life
timeFrame: Measured at study baseline and weeks 3 and 4 of each crossover
measure: Change in health-related quality of life
timeFrame: Measured at study baseline and weeks 3 and 4 of each crossover
measure: Change in health-related quality of life
timeFrame: Measured at study baseline and weeks 3 and 4 of each crossover
measure: Effect of nabilone on sleep quality
timeFrame: Measured at study baseline and weeks 3 and 4 of each crossover
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: Seven Oaks General Hospital
state: Manitoba
Study officials:
affiliation: University of Manitoba
name: David Collister, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: