Dosage Determination Trial for Indigo Naturalis Extract in Oil Ointment

Study Overview
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Brief Summary
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The use of refined indigo naturalis (indigo naturalis extract in oil, INEO)ointment to treat psoriasis has been proven effective in our previous study. This study aims to evaluate the efficacy and safety of INEO ointment, and further determine the optimal concentration of INEO ointment (per gram of ointment containing either 200 μg, 100 μg, 50 μg or 10 μg of indirubin) in treatment of various local skin signs and thickness of psoriasis plaque.

Detailed Description
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The use of indigo naturalis ointment to treat psoriasis has been proven effective in our previous clinical studies which demonstrated the efficacy and safety of topical indigo naturalis ointment, showing its ability to provide significant improvement of psoriatic skin lesions. We developed a new formulation in which indigo naturalis powder is refined and reduces the blue discoloration of skin and clothes, making the treatment more user-friendly. We had observed an equivalent efficacy of the refined form of indigo naturalis (INEO) ointment on treating psoriasis as the crude form. However, it is necessary to determine an appropriate dosage of the refined form regarding its efficacy and safety. This is a double-blind, 4-arm parallel study. The aim of this study is To determine an appropriate dosage of indirubin in INEO ointment, regarding its efficacy and safety. To evaluate the efficacy of INEO ointment in different local skin signs of plaque lesions. To evaluate the efficacy of INEO in different traditional Chinese medicine clinical syndromes of psoriasis vulgaris. To investigate the effects of INEO ointment on the immune system. To evaluate the effects of INEO ointment in improving quality of life after treatment.

Official Title
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Evaluation of the Efficacy and Safety of Indigo Naturalis Extract in Oil in the Topical Therapy of Psoriasis Vulgaris: Dosage Determination

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: Indirubin 200μg/g
* Drug: Indirubin 100 μg/g
* Drug: Indirubin 50 μg/g
* Drug: Indirubin 10 μg/g


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 20 - 65 years, men or women. Diagnosed as mild to moderate plaque-type psoriasis by the dermatologist, with psoriasis for a minimum of 1 year. Plaque psoriasis involving <20% of BSA and with PASI <20. Female patients of child-bearing age with negative pregnancy test at screening. Female patients of childbearing age who have agreed to continue using birth control measures approved by the investigator and agree not to lactate for the duration of the study. Willingness to comply with study protocol. With signed informed consent form. Exclusion Criteria: With history of topically or systematically hypersensitive to indigo naturalis or its excipient in ointment. With history of sensitivity to Chinese herb. Received systematic treatment for psoriasis within 4 weeks. Received topical treatment for psoriasis within 2 weeks. With abnormal liver or renal function, clinically significant abnormalities in hematology, severe uncontrolled metabolic syndrome,psychiatric disease, cancer or AIDS. Patients with pustular or erythrodermic psoriasis.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Indirubin 200 μg/g<br>per gram of ointment contains 200 μg of indirubin | Drug: Indirubin 200μg/g<br>* Dosage form: Ointment Dose(s): Each gram of ointment containing 200 μg of indirubin Dosing schedule: apply 0.5 g of ointment per 10 x 10 cm psoriatic lesion twice daily<br>* Other names: INEO ointment: Indirubin 200 μg/g;|
| Active Comparator: Indirubin 100 μg/g<br>per gram of ointment contains 100 μg of indirubin | Drug: Indirubin 100 μg/g<br>* Dosage form: Ointment Dose(s): Each gram of ointment contains 100 μg of indirubin Dosing schedule: apply 0.5 g of ointment per 10 x 10 cm psoriatic lesion twice daily<br>* Other names: INEO ointment: Indirubin 100 μg/g;|
| Active Comparator: Indirubin 50 μg/g<br>per gram of ointment contains 50 μg of indirubin | Drug: Indirubin 50 μg/g<br>* Dosage form: Ointment Dose(s): Each gram of ointment contains 50 μg of indirubin Dosing schedule: apply 0.5 g of ointment per 10 x 10 cm psoriatic lesion twice daily<br>* Other names: INEO ointment: Indirubin 50 μg/g;|
| Active Comparator: Indirubin 10 μg/g<br>per gram of ointment contains 10 μg of indirubin | Drug: Indirubin 10 μg/g<br>* Dosage form: Ointment Dose(s): Each gram of ointment contains 10 μg of indirubin Dosing schedule: apply 0.5 g of ointment per 10 x 10 cm psoriatic lesion twice daily<br>* Other names: INEO ointment: Indirubin 10 μg/g;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the mean percentage change of Psoriasis Areas Severity Index (PASI) from baseline at week 8 between groups | Mean change of total score (range 0-72) Percentage change of PASI Individual scores of scaling, erythema, and elevation by sites Percentage of responder (>50% of improvement, defined as clinical meaningful) and non-responder (less then 50% of improvement) Percentage of subjects achieving clear or almost clear (defined as PASI >90% of improvement) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body surface area (BSA)involved | Compare the BSA involved change from baseline on target psoriatic lesion(cm2) Compare the percentage change from baseline on target psoriatic lesion | 8 weeks | 
| Psoriasis Severity Index (PSI) | Mean change of total score (range 0-12) of the target psoriatic plaque Percentage change of PSI score of the target psoriatic plaque Clearing percentage of target psoriatic plaque (the target plaque before treatment is defined as 100%, and the clearance of lesion is defined as 0%) | 8 weeks | 
| Efficacy in various local skin signs | Thickness: thin (<0.05 mm), intermediate (≥0.05 to <1.0 mm) or thick (≥1.0 mm) Size: small (<5 cm in diameter), large (>5 cm in diameter) or concurrent (i.e., two type sizes exist) Erythema (redness): light red (ruddier (light red) than peripheral normal skin) or dark red (redder (scarlet) than peripheral normal skin) | 8 weeks | 
| Efficacy in different traditional Chinese medicine (TCM) clinical syndromes of psoriasis by PASI/PSI: | Blood-heat (血熱) syndrome Blood-dryness (血燥) syndrome Blood-stasis (血瘀) syndrome | 8 weeks | 
| Physician's Global Assessment (PGA) | 0 = no sign of psoriasis, 1 = almost clear, 2 = mild, 3 = moderate, 4 = moderate to severe, and 5 = severe | 8 weeks | 
| Subject's Global Assessment (SGA) | 0 = cleared, 1 = excellent, 2 = good, 3 = fair, 4 = poor, and 5 = worse | 8 weeks | 
| Dermatology Life Quality Index (DLQI) questionnaire |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Indigo naturalis extract in oil