Clinical trial NCT06435299: Efficacy and Tolerance of Cannabidiol in Patients with Severe Pruritus: a Multicenter, Double-blind, Randomized, Placebo-controlled Study
Official title: Efficacy and Tolerance of Cannabidiol in Patients with Severe Pruritus: a Multicenter, Double-blind, Randomized, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Pruritus
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
First posted: 2024-05-30
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Pruritus is defined as an unpleasant sensation leading to the need to scratch. Medications for pruritus are much less effective than those used for pain and it is imperative to find new therapeutic options.

Over the last 20 years, the understanding of the pathophysiology of pruritus has progressed significantly, opening new possible therapeutic fields. Among these, cannabinoids seem very promising because the physiological inhibitory role of endocannabinoids, mainly produced by neurons, has been well demonstrated. Data from the literature suggest that the antipruritic effects of cannabinoids are due to a combination of effects on neuronal activation, transmission along the afferent pathway, and local modulation of keratinocytes and mast cells. The antipruritic effect is peripheral and central, through modulation of CB1, CB2 or TRPV1 channels. CB1 and CB2 receptors are specific cannabinoid receptors, CB1 being present at the central and peripheral level while CB2 is only peripheral and very present in the skin. Cannabinoids can also bind to TRPV1, and thus inhibit neurogenic inflammation by antagonizing or stabilizing this ion channel, which prevents neuronal activation by pruritogenic mediators. Phytocannabinoids are derived from cannabis and are used for a variety of purposes, with their development for medical purposes expanding rapidly. The two best known are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC binds to TRPV1, CB2 and CB1, the activation of the latter being at the origin of parallel psychotropic effects. CBD binds mainly to TRPV1, which allows us to expect very favorable effects on pruritus, neurogenic inflammation and skin pain, without fearing side effects of this type.

A limited number of studies suggest that cannabinoids may be useful topically or systemically, in humans or animals, but no comparative study with placebo has been performed. These encouraging results have been observed in cases of induced pruritus, idiopathic pruritus, eczema, uremic pruritus, cholestatic pruritus, prurigo, sensitive skin or even epidermolysis bullosa.

Currently, the ANSM is conducting an evaluation of the effects of medical cannabis on severe pain. We propose to evaluate the effects on severe pruritus in a randomized placebo-controlled study one of the products chosen by the ANSM in this context, the oil LITTLE GREEN PHARMA, which we choose for its dominant CBD ratio (THC \< 5 mg/ml, CBD \> 5 mg/ml).


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Severe pruritus, defined by a mean WI-NRS score ≥7/10 (evaluated on one week before inclusion, regardless of the cause of the pruritus
* Insufficient relief (WI-NRS ≥7/10 ) or poor tolerance (adverse effects) of accessible drug and non-drug therapies
* Stable treatment (for treatment of the prurit) for at least 6 weeks
* Affiliated or benefiting of a social security
* Informed consent (personally dated and) signed by the participant or any representatives (impartial witness/trusted person)

Exclusion Criteria:

* Patients unable to consent.
* Patients refusing to participate in research.
* Patients under guardianship or conservatorship.
* Personal history of psychotic disorders.
* Severe hepatic impairment, defined as prothrombin level \<50% or with predictive biological impairment.
* Moderate to severe renal impairment, with an estimated glomerular filtration rate ≤ 44 mL/min/1.73 m².
* Severe cardiovascular or cerebrovascular disease, including history of myocardial infarction or stroke.
* Pregnant or breastfeeding women.
* Lack of understanding of questionnaires or inability to follow up.
* Women of childbearing potential unwilling to use appropriate contraception.
* Cannabinoid use outside the clinical trial
* Use of cannabis or its derivatives less than one week before inclusion
* History of hypersensitivity or allergy to any cannabinoid product.
* Allergy to nuts.

Primary outcomes:
measure: WI-NRS change
timeFrame: Week 0
measure: WI-NRS change
timeFrame: Week 6
Secondary outcomes:
measure: WI-NRS change from W0 to W2
timeFrame: Week 0
measure: WI-NRS change from W0 to W2
timeFrame: Week 2
measure: WI-NRS change from W2 to W6
timeFrame: Week 2
measure: WI-NRS change from W2 to W6
timeFrame: Week 6
measure: ItchyQoL change from W0 to W2
timeFrame: Week 0
measure: ItchyQoL change from W0 to W2
timeFrame: Week 2
measure: ItchyQoL change from W2 to W6
timeFrame: Week 2
measure: ItchyQoL change from W2 to W6
timeFrame: Week 6
measure: Chronic Itch Burden Scale change from W0 to W2
timeFrame: Week 0
measure: Chronic Itch Burden Scale change from W0 to W2
timeFrame: Week 2
measure: Chronic Itch Burden Scale change from W2 to W6
timeFrame: Week 2
measure: Chronic Itch Burden Scale change from W2 to W6
timeFrame: Week 6
measure: Treatment adverse events
timeFrame: Week 0
measure: Treatment adverse events
timeFrame: Week 2
measure: Treatment adverse events
timeFrame: Week 4
measure: Treatment adverse events
timeFrame: Week 6
measure: Treatment adverse events
timeFrame: Week 8
measure: Treatment Observance Rate
timeFrame: Week 6
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: La Roche Sur Yon
country: France
facility: CHD Vendée
city: La Rochelle
country: France
facility: Groupe Hospitalier La Rochelle
city: Nantes
country: France
facility: CHU de Nantes
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rennes
country: France
facility: CHU de Rennes
city: Tours
country: France
facility: CHRU de Tours
Study officials:
References: