Grant: Project Grant - Priority Announcement: Patient-Oriented Research

Itching associated with kidney disease affects more than half of patients on dialysis. It is a top research priority because of its negative impact on quality of life. Why itching is so common in dialysis patients is not fully understood but it is likely due to changes in skin and the accumulation of toxins normally cleared by the kidney leading to nervous and immune system dysfunction. Several therapies have been studied to reduce itching in dialysis patients but most clinical trials evaluating these therapies have been small with design issues resulting in bias and uncertainty about how well these drugs actually work. Medications thought to be effective are limited by their side effects which are common even with appropriate dosing. Even with effective treatments, residual, bothersome itch is common. Cannabis has been used to treat other skin disorders such as eczema, psoriasis and chronic itch. It has been shown to decrease skin irritation and swelling by modulating the immune system and inhibiting itch pathways. DISCO-POT will compare oral nabilone and topical nabilone to placebos (non-active drugs that looks, smell and taste the same as their comparators) to determine if nabilone is safe and effective at reducing symptoms of itch in dialysis patients. Nabilone is a synthetic form of cannabis that mimics the actions of tetrahydrocannabinol (THC), the main drug in cannabis. The trial will use a "n-of-1" design in which individual patients are randomly assigned (like flipping a coin) to each treatment regimen multiple times in different orders. Patients and their physicians will not be aware of which treatment they are receiving (i.e. they are "blinded") until the end of the study where their results will be reviewed so a treatment decision can be made (unlike traditional clinical trials). N-of-1 trials will then be combined to estimate population-based treatment effects to inform clinical decision-making for patients outside of the clinical trial.