## Protocol Section
### Identification Module
**NCT ID:** NCT06435299

**Acronym:** CANNABITCH

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

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

#### Organization Study ID Info
**ID:** 29BRC23.0164
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Brest
### Status Module
#### Completion Date
**Date:** 2024-09-28

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-29

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-09-14

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-03-27
**Study First Submit QC Date:** 2024-05-29
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Brest

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Pruritus

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** TRIPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

**Primary Purpose:** SUPPORTIVE_CARE

#### Enrollment Info

**Count:** 218

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: Cannabis oil

**Label:** Cannabis oil

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Drug: Placebo

**Label:** PLACEBO

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cannabis oil

**Description:** 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)

**Name:** Cannabis oil

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- PLACEBO

**Description:** 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)

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** WI-NRS change

**Time Frame:** Week 0

**Description:** 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.

**Measure:** WI-NRS change

**Time Frame:** Week 6

#### Secondary Outcomes

**Description:** - 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.

**Measure:** WI-NRS change from W0 to W2

**Time Frame:** Week 0

**Description:** - 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.

**Measure:** WI-NRS change from W0 to W2

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** ItchyQoL change from W0 to W2

**Time Frame:** Week 0

**Description:** - 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)

**Measure:** ItchyQoL change from W0 to W2

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** ItchyQoL change from W0 to W2

**Time Frame:** Week 0

**Description:** - 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)

**Measure:** ItchyQoL change from W0 to W2

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** ItchyQoL change from W0 to W6

**Time Frame:** Week 0

**Description:** - 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)

**Measure:** ItchyQoL change from W0 to W6

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** ItchyQoL change from W0 to W6

**Time Frame:** Week 4

**Description:** - 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)

**Measure:** ItchyQoL change from W0 to W6

**Time Frame:** Week 6

**Description:** - 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)

**Measure:** ItchyQoL percent change from W0 to W6

**Time Frame:** Week 0

**Description:** - 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)

**Measure:** ItchyQoL percent change from W0 to W6

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** ItchyQoL percent change from W0 to W6

**Time Frame:** Week 4

**Description:** - 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)

**Measure:** ItchyQoL percent change from W0 to W6

**Time Frame:** Week 6

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W2

**Time Frame:** Week 0

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W2

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W2

**Time Frame:** Week 0

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W2

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W6

**Time Frame:** Week 0

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W6

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W6

**Time Frame:** Week 4

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale evolution from W0 to W6

**Time Frame:** Week 6

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W6

**Time Frame:** Week 0

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W6

**Time Frame:** Week 2

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W6

**Time Frame:** Week 4

**Description:** - 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)

**Measure:** Chronic Itch Burden Scale change from W0 to W6

**Time Frame:** Week 6

**Description:** - Incidence and severity of treatment-emergent adverse events.

**Measure:** Treatment adverse events

**Time Frame:** Week 0

**Description:** - Incidence and severity of treatment-emergent adverse events.

**Measure:** Treatment adverse events

**Time Frame:** Week 2

**Description:** - Incidence and severity of treatment-emergent adverse events.

**Measure:** Treatment adverse events

**Time Frame:** Week 4

**Description:** - Incidence and severity of treatment-emergent adverse events.

**Measure:** Treatment adverse events

**Time Frame:** Week 6

**Description:** - Incidence and severity of treatment-emergent adverse events.

**Measure:** Treatment adverse events

**Time Frame:** Week 8

### Eligibility Module

**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

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

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** laurent.misery@chu-brest.fr

**Name:** Laurent MISERY, PU-PH

**Role:** CONTACT

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012871

- Term: Skin Diseases

- ID: D000012877

- Term: Skin Manifestations

### Condition Browse Module - Browse Branches

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M14396

- Name: Pruritus

- Relevance: HIGH

- As Found: Pruritus

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15680

- Name: Skin Manifestations

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000011537

- Term: Pruritus

### Intervention Browse Module - Browse Branches

- Abbrev: AntiConv

- Name: Anticonvulsants

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M5445

- Name: Cannabidiol

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
