Evaluation of the Antipruritic Effect of Elidel (Pimecrolimus) in Non-atopic Pruritic Disease

Study Overview
=================
Brief Summary
-----------------
The development of the topical calcineurin inhibitor pimecrolimus resulted in a significant improvement in the treatment of atopic dermatitis. In addition, an excellent amelioration of pruritus could be regularly observed. Up to now, several itchy dermatoses such as chronic irritative hand dermatitis, rosacea, graft-versus-host-disease, lichen sclerosus, prurigo simplex, scrotal eczema, and inverse psoriasis were reported as single cases also to respond to a pimecrolimus treatment. In prurigo nodularis, pruritus is the main symptom and it is of immediate importance to find an effective antipruritic therapy. Pruritus is regularly severe and therapy refractory to topical steroids or systemic antihistamines. Capsaicin cream is one effective possibility to reduce the itch in these diseases. However, it has to be applied 3 to 6 times daily, rubs off on the clothing and induces burning in erosions. In addition, since no commercial preparation is available, it has to be prescribed in several concentrations. The application of pimecrolimus seems to be promising since it has to be applied twice daily only. Especially in prurigo nodularis we expect a good response as we could demonstrate in single patients. Furthermore it has been published recently that Tacrolimus, another calcineurin inhibitor has been successfully used in the treatment of six patients with prurigo nodularis. This study is designed to compare the efficacy and safety of pimecrolimus 1% cream and hydrocortisone 1% cream in prurigo nodularis and to investigate the mode of action of the antipruritic effect of the drugs.

Detailed Description
-----------------
Patients will be treated with pimecrolimus cream 1% and hydrocortisone cream 1% twice daily for 8 weeks on diseased skin in a double-blind, randomized within patient comparison (left arm pimecrolimus, right arm hydrocortisone or vice versa). Patients will then enter a 4-week treatment free follow-up period. The overall study duration is 12 months. The study population will consist of a representative group of 30 adult patients (18 - 70 years of age) with prurigo nodularis from one center in Germany. Inclusion criteria Age: 18 - 70 years Diagnosis: Prurigo nodularis Pruritus intensity above VAS 3 (Visual analogue scale 0 to 10) Nodules on arms and legs (target areas: arms) No effective current external or internal antipruritic medication Signed informed consent Exclusion criteria prurigo nodularis with massive excoriations and/or local infections atopic dermatitis, predisposition for atopic dermatitis Itch intensity below VAS 4 (visual analoge scale 0 to 10) Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG test. Pregnancy should be ruled out before stating the study by a b-subunit HCG test. Females of childbearing potential and not practicing a medically approved, highly effective (low failure rate) method of contraception during and up to at least 4 weeks after the end of treatment. 'Medically approved' contraception may include implants, injectables, combined oral contraceptives, some IUDs (e.g. intrauterine device), sexual abstinence or if the woman has a vasectomized partner. active psychosomatic and psychiatric diseases History of active malignancy of any organ system actual diseases which need therapy and may induce pruritus (e.g. deficiency of iron, zinc) Systemic immunosuppression Topical use of tacrolimus, pimecrolimus, steroids or capsaicin within 2 weeks prior to study entry current and past (within 2 weeks prior to study entry) systemic use of antihistamines, steroids, cyclosporin A and other immunosuppressants, paroxetin, fluvoxamine (selective serotonin reuptake- inhibitors, study possible in case of medication since 6 months due to depression without having any Antipruritic effect) naltrexone and UV-therapy. wound healing disturbances, disposition for keloids, current medication which leads to increased bleeding during procedure e.g. acetylsalicylic acid (ASS), marcumar (no suction blister possible) History of hypersensitivity to pimecrolimus 1% cream or hydrocortisone 1% cream Participation in other clinical studies within the last 4 weeks

Official Title
-----------------
Evaluation of the Antipruritic Effect of Elidel (Pimecrolimus) in Non-atopic Pruritic Disease

Conditions
-----------------
Prurigo Nodularis

Intervention / Treatment
-----------------
* Drug: Pimecrolimus
* Drug: Hydrocortisone
* Drug: Pimecrolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 18 - 70 years Diagnosis: Prurigo nodularis Pruritus intensity above VAS 3 (Visual analoge scale 0 to 10) Nodules on arms and legs (target areas: arms) No effective current external or internal antipruritic medication Signed informed consent Exclusion Criteria: prurigo nodularis with massive excoriations and/or local infections atopic dermatitis, predisposition for atopic dermatitis Itch intensity below VAS 4 (visual analoge scale 0 to 10) Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG test. Pregnancy should be ruled out before stating the study by a b-subunit HCG test. Females of childbearing potential and not practicing a medically approved, highly effective (low failure rate) method of contraception during and up to at least 4 weeks after the end of treatment. 'Medically approved' contraception may include implants, injectables, combined oral contraceptives, some IUDs (e.g. intrauterine device), sexual abstinence or if the woman has a vasectomized partner. active psychosomatic and psychiatric diseases History of active malignancy of any organ system actual diseases which need therapy and may induce pruritus (e.g. deficiency of iron, zinc) Systemic immunosuppression Topical use of tacrolimus, pimecrolimus, steroids or capsaicin within 2 weeks prior to study entry current and past (within 2 weeks prior to study entry) systemic use of antihistamines, steroids, cyclosporin A and other immunosuppressants, paroxetin, fluvoxamine (selective serotonin reuptake- inhibitors, study possible in case of medication since 6 months due to depression without having any Antipruritic effect) naltrexone and UV-therapy. wound healing disturbances, disposition for keloids, current medication which leads to increased bleeding during procedure e.g. acetylsalicylic acid (ASS), marcumar (no suction blister possible) History of hypersensitivity to pimecrolimus 1% cream or hydrocortisone 1% cream Participation in other clinical studies within the last 4 weeks

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: I<br>Interindividual design: active and comparator (one side each) applied twice daily | Drug: Pimecrolimus<br>* twice daily topical<br>* Other names: Elidel Cream 1%;Drug: Pimecrolimus<br>* topical application as a cream twice daily<br>* Other names: Elidel 1% Cream;|
| Active Comparator: II Hydrocortisone<br>Hydrocortisone, twice daily | Drug: Hydrocortisone<br>* twice daily topical<br>* Other names: Hydrocortisone HExal;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypothesis: pimecrolimus is superior in the reduction of the itch intensity on a visual analogue scale (VAS) compared to hydrocortisone cream 1%. H1: mean value VAS pimecrolimus < mean value VAS hydrocortisone |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of total symptom score (papule, nodules, excoriations, crusting, erythema) scored from 0-3 for each single symptom |  | 12 months | 
| Change of skin neuropeptide content in suction blisters |  | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prurigo nodularis