Efficacy and Tolerance of Cannabidiol in Patients with Severe Pruritus: a Multicenter, Double-blind, Randomized, Placebo-controlled Study

Phase 3Not Yet RecruitingNCT06435299

University Hospital, Brest218 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (7)

CHU Angers

Angers, France, France

CHD Vendée

La Roche-sur-Yon, France, France

Groupe Hospitalier La Rochelle

La Rochelle, France, France

CHU de Nantes

Nantes, France, France

CHU de Poitiers

Poitiers, France, France

CHU de Rennes

Rennes, France, France

CHRU de Tours

Tours, France, France

Outcomes

Primary Outcomes

WI-NRS change

Binary outcome (success or failure). Success is defined by a reduction of 30% in WINRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) from the inclusion visit to week 6.

Time frame: Week 0

WI-NRS change

Time frame: Week 6

Secondary Outcomes

WI-NRS change from W0 to W2

\- Proportion of patients achieving at least a weekly mean reduction of 4 points in WI-NRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) score from inclusion visit to week 2

Time frame: Week 0

WI-NRS change from W0 to W2

Time frame: Week 2

WI-NRS change from W2 to W6

Proportion of patients achieving at least a weekly mean reduction of 4 points in WI-NRS (Worst Itching Intensity Numerical Rating Scale - On a scale of 0 (no itch) to 10 (worst itch imaginable)) score from week 2 to week 6.

Time frame: Week 2

WI-NRS change from W2 to W6

Time frame: Week 6

ItchyQoL change from W0 to W2

\- Change in ItchyQoL score from inclusion (= Week 0) visit to week 2 (The ItchyQoL questionnaire contains 22 items, and each item is rated on a 5-point scale, ranging from 1 = never to 5 = all the time)

Time frame: Week 0

ItchyQoL change from W0 to W2

Time frame: Week 2

ItchyQoL change from W2 to W6

\- Percent change in ItchyQoL score from Week 2 visit to week 6 (The ItchyQoL questionnaire contains 22 items, and each item is rated on a 5-point scale, ranging from 1 = never to 5 = all the time)

Time frame: Week 2

ItchyQoL change from W2 to W6

\- Change in ItchyQoL score from Week 2 visit to week 6.(The ItchyQoL questionnaire contains 22 items, and each item is rated on a 5-point scale, ranging from 1 = never to 5 = all the time)

Time frame: Week 6

Chronic Itch Burden Scale change from W0 to W2

\- Change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 2 (10 questions rated from "Not at all" to "Very much" on patient itching)

Time frame: Week 0

Chronic Itch Burden Scale change from W0 to W2

\- Change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 2 (10 questions rated from "Not at all" to "Very much" on patient itching)

Time frame: Week 2

Chronic Itch Burden Scale change from W2 to W6

\- Percent change in Chronic Itch Burden Scale - 10 from Week 2 visit to week 6 (10 questions rated from "Not at all" to "Very much" on patient itching)

Time frame: Week 2

Chronic Itch Burden Scale change from W2 to W6

\- Percent change in Chronic Itch Burden Scale - 10 from Week 2 visit to week 6 (10 questions rated from "Not at all" to "Very much" on patient itching)

Time frame: Week 6

Treatment adverse events