Efficacy and Tolerance of THC 25: CBD 25 in Patients With Severe Pruritus: a Multicenter, Double-blind, Randomized, Placebo-controlled Study

Phase 2Not Yet RecruitingNCT06435299

University Hospital, Brest218 enrolled

Overview

Chronic pruritus affects 10-20% of the population and causes a major reduction in quality of life, comparable to pain, with significant psychological, social, and functional consequences. Current treatments are often insufficient, highlighting the urgent need for new therapeutic options. Recent advances in the pathophysiology of itch have shown the involvement of the endocannabinoid system (CB1, CB2, and TRPV1 receptors) in modulating itch signal transmission and cutaneous inflammation. Cannabinoids, particularly the balanced CBD:THC combination, appear promising as they provide both central and peripheral antipruritic effects, while CBD helps mitigate the psychotropic side effects of THC. Preclinical studies and limited clinical data suggest efficacy across various forms of pruritus (dermatological, uremic, cholestatic), though robust controlled trials are still lacking. Evidence from nabiximols (1:1 CBD:THC spray) in other conditions such as neuropathic pain and spasticity further supports the rationale for this approach. Therefore, sublingual LGP THC25:CBD25 oil has been selected for its balanced ratio, simple administration route, and expected tolerability, to evaluate its efficacy and safety in the treatment of chronic pruritus.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

218

Conditions

Pruritus

Interventions

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.

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