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

NCT ID: NCT06435299

Last Updated: 2025-02-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 218 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-01
• Study Completion Date: 2027-07-01

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).

Conditions

Pruritus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Cannabis oil

Cannabis oil 50mg/mL arm :

An auto-titration phase will take place during the first 14 days of treatment: 0.2 ml on the first day then increase of 0.2 ml every 2 days in 2 daily doses, that is to say 1.4 ml/day maximum.

If any tolerable side-effects occurred, patients were advised not to increase the dose; if intolerable side-effects occurred, dose reduction was advised.

After initial titration, the dose will then be maintained for 4 consecutive weeks.

Group Type: EXPERIMENTAL

Cannabis oil

Intervention Type: DRUG

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

Placebo arm :

An auto-titration phase will take place during the first 14 days of treatment: 0.2 ml on the first day then increase of 0.2 ml every 2 days in 2 daily doses, that is to say 1.4 ml/day maximum.

If any tolerable side-effects occurred, patients were advised not to increase the dose; if intolerable side-effects occurred, dose reduction was advised.

After initial titration, the dose will then be maintained for 4 consecutive weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

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)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Brest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Countries

France

Central Contacts

Laurent MISERY, PU-PH

Role: CONTACT

laurent.misery@chu-brest.fr

Facility Contacts

YANNICK LE CORRE, MD

Role: primary

yalecorre@chu-angers.fr

02 41 35 34 19

Carole POIRAUD, MD

Role: primary

Carole.poiraud@ght85.fr

02 51 44 61 83

Cécile FRENARD, MD

Role: primary

Cecile.frenard@ght-atlantique17.fr

05 45 45 51 83

Sebastien BARBAROT, MD-PHD

Role: primary

sebastien.barbarot@chu-nantes.fr

02 40 08 40 86

Ewa HAINAUT, MD

Role: primary

Ewa.HAINAUT@chu-poitiers.fr

05 49 44 44 59

Maxime FOUCHARD, MD

Role: primary

maxime.fouchard@chu-rennes.fr

02 99 28 43 49

Laurent MACHET, MD-PHD

Role: primary

machet@univ-tours.fr

02 47 47 87 73

Other Identifiers

29BRC23.0164

Identifier Type: -

Identifier Source: org_study_id