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

Pruritus Clinical Trial

— CANNABITCH  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06435299
• Other study ID #: 29BRC23.0164
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 1, 2024
• Est. completion date: September 28, 2024

Study information

• Verified date: May 2024
• Source: University Hospital, Brest
• Contact: Laurent MISERY, PU-PH
• Email: laurent.misery[@]chu-brest.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 218
• Est. completion date: September 28, 2024
• Est. primary completion date: September 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Exclusion Criteria:

• Inability of the patient to give free and informed consent

• Personal history of psychotic disorders

• Severe hepatic impairment (prothrombin level <50%)

• Moderate to severe renal impairment (estimated glomerular filtration rate = 44 mL/min/1.73 m2 ?)

• Disease or history of severe cardiovascular or cerebrovascular disorders (myocardial infraction, stroke)

• Pregnant or breastfeeding woman

• Lack of understanding of questionnaires or inability to follow up - Inability of the patient to give free and informed consent

• Personal history of psychotic disorders

• Severe hepatic impairment (prothrombin level >50%) or predictive biological impairment

• Severe renal impairment (Estimated glomerular filtration rate = 44 mL/min/1.73 m2 ? )

• Severe cardiovascular (myocardial infarction, cardiovascular accident) or cerebrovascular disease or history of such disease

• Pregnant or breastfeeding woman

• Lack of understanding of questionnaires or inability to follow up

• 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

Related Conditions & MeSH terms

• Pruritus

Intervention

Drug:
• Cannabis oil
Patients in this arm will have to take Cannabis oil (50mg/mL) twice a day with the daily dose estimated during auto titration phase (from W0 to W2)
• Placebo
Patients in this arm will have to take Placebo oil twice a day with the daily dose estimated during auto titration phase (from W0 to W2)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Brest

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 0
Primary	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.	Week 6
Secondary	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.	Week 0
Secondary	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 (= Week 0) visit to week 2.	Week 2
Secondary	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)	Week 0
Secondary	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)	Week 2
Secondary	ItchyQoL change from W0 to W2	- Percent 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)	Week 0
Secondary	ItchyQoL change from W0 to W2	- Percent 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)	Week 2
Secondary	ItchyQoL change from W0 to W6	- Change in ItchyQoL score from inclusion (= Week 0) 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)	Week 0
Secondary	ItchyQoL change from W0 to W6	- Change in ItchyQoL score from inclusion (= Week 0) 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)	Week 2
Secondary	ItchyQoL change from W0 to W6	- Change in ItchyQoL score from inclusion (= Week 0) 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)	Week 4
Secondary	ItchyQoL change from W0 to W6	- Change in ItchyQoL score from inclusion (= Week 0) 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)	Week 6
Secondary	ItchyQoL percent change from W0 to W6	- Percent change in ItchyQoL score from inclusion (= Week 0) 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)	Week 0
Secondary	ItchyQoL percent change from W0 to W6	- Percent change in ItchyQoL score from inclusion (= Week 0) 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)	Week 2
Secondary	ItchyQoL percent change from W0 to W6	- Percent change in ItchyQoL score from inclusion (= Week 0) 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)	Week 4
Secondary	ItchyQoL percent change from W0 to W6	- Percent change in ItchyQoL score from inclusion (= Week 0) 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)	Week 6
Secondary	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)	Week 0
Secondary	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)	Week 2
Secondary	Chronic Itch Burden Scale change from W0 to W2	- Percent 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)	Week 0
Secondary	Chronic Itch Burden Scale change from W0 to W2	- Percent 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)	Week 2
Secondary	Chronic Itch Burden Scale change from W0 to W6	- Change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 6.(10 questions rated from "Not at all" to "Very much" on patient itching)	Week 0
Secondary	Chronic Itch Burden Scale change from W0 to W6	- Change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 6.(10 questions rated from "Not at all" to "Very much" on patient itching)	Week 2
Secondary	Chronic Itch Burden Scale change from W0 to W6	- Change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 6.(10 questions rated from "Not at all" to "Very much" on patient itching)	Week 4
Secondary	Chronic Itch Burden Scale evolution from W0 to W6	- Change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 6. (10 questions rated from "Not at all" to "Very much" on patient itching)	Week 6
Secondary	Chronic Itch Burden Scale change from W0 to W6	- Percent change and percent change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 6.(10 questions rated from "Not at all" to "Very much" on patient itching)	Week 0
Secondary	Chronic Itch Burden Scale change from W0 to W6	- Percent change and percent change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 6.(10 questions rated from "Not at all" to "Very much" on patient itching)	Week 2
Secondary	Chronic Itch Burden Scale change from W0 to W6	- Percent change and percent change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 6.(10 questions rated from "Not at all" to "Very much" on patient itching)	Week 4
Secondary	Chronic Itch Burden Scale change from W0 to W6	- Percent change and percent change in Chronic Itch Burden Scale - 10 from inclusion (= Week 0) visit to week 6.(10 questions rated from "Not at all" to "Very much" on patient itching)	Week 6
Secondary	Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 0
Secondary	Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 2
Secondary	Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 4
Secondary	Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 6
Secondary	Treatment adverse events	- Incidence and severity of treatment-emergent adverse events.	Week 8