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

NCT06435299 | Not Yet Recruiting Phase 3

• 1 other identifier: 29BRC23.0164
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 7

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (18)

• WI-NRS change from W0 to W2

  Week 0

• WI-NRS change from W0 to W2

  Week 2

• WI-NRS change from W2 to W6

  Week 2

• WI-NRS change from W2 to W6

  Week 6

• ItchyQoL change from W0 to W2

  Week 0

Study Arms (2)

Cannabis oil

EXPERIMENTAL

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.

Drug: Cannabis oil

PLACEBO

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Cannabis oil 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)

Cannabis oil

Placebo 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)

PLACEBO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• 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)

You may not qualify if:

• 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
• History of hypersensitivity or allergy to any cannabinoid product.
• Allergy to nuts.

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (7)

CHU Angers

Angers, France, 49000, France

Location

CHD Vendée

La Roche-sur-Yon, France, 85925, France

Location

Groupe Hospitalier La Rochelle

La Rochelle, France, 17300, France

Location

CHU de Nantes

Nantes, France, 44093, France

Location

CHU de Poitiers

Poitiers, France, 86000, France

Location

CHU de Rennes

Rennes, France, 35033, France

Location

CHRU de Tours

Tours, France, 37044, France

Location

MeSH Terms

Conditions

Pruritus

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Laurent MISERY, PU-PH

CONTACT

laurent.misery@chu-brest.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2024
• First Posted: May 30, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 5, 2025

Record last verified: 2025-02

Locations

FR (7)