Indigo Naturalis in Treating Atopic Dermatitis Topically

Efficacy and Safety of Topical Indigo Naturalis in Treating Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that most commonly occurs in children. The aims of this project are:

1. To evaluate the efficacy of indigo naturalis ointment in treating AD topically;
2. To evaluate the safety of indigo naturalis ointment in treating AD topically;
3. To investigate whether indigo naturalis ointment treatment is associated with a change in total IgE, cytokines, eosinophils, and CRP in patients with AD;
4. To evaluate whether indigo naturalis ointment treatment improves the quality of life in patients with AD.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Indigo naturalis ointment; Drug: Placebo

Detailed Description

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that most commonly occurs in children. AD is characterized by itchy and dry skin that affects approximately 5 to 20% of children in the world. Currently, corticosteroids are the most widely prescribed medication in treating AD; however, there are concerns regarding the side effects such as skin atrophy, telangiectasia, striae, folliculitis and adrenocortical suppression that inhibits growth in children. Many patients and families seek complementary and alternative medications such as traditional Chinese medicine (TCM). In TCM, indigo naturalis has been used to treat various infectious and inflammatory skin diseases for hundreds of years. Ancient TCM literature has recorded that indigo naturalis is also effective in treating facial eczema (AD) in infants.

The aims of this project are: (1) To evaluate the efficacy of indigo naturalis ointment in treating AD topically; (2) To evaluate the safety of indigo naturalis ointment in treating AD topically; (3) To investigate whether indigo naturalis ointment treatment is associated with a change in total IgE, cytokines, eosinophils, and CRP in patients with AD; (4) To evaluate whether indigo naturalis ointment treatment improves the quality of life in patients with AD.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Kelung, Taiwan, 204
    • Chang Gung Memorial Hospital at Keelung
  • Taipei, Taiwan, 105
    • Chang Gung Memorial Hospital at Taipei
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital at Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Between 6 and 65 years old, female or male.
2. Atopic dermatitis fulfilling the diagnostic criteria of Williams et al.
3. Atopic dermatitis involving <40% of BSA. (Base on the BSA result of Screening)
4. An Investigator's Global Assessment (IGA) score of 2, 3 or 4 which corresponds to mild, moderate or severe disease. (Base on the IGA result of Screening)
5. Female patients of child-bearing age with negative pregnancy test at screening.
6. Female patients of child-bearing age that agree to continue using birth control measures approved by the investigator and agree not to lactate for the duration of the study.
7. Agree to only receive stable doses of an additive-free, basic bland emollient for at least 7 days before baseline (day0)
8. Willing to comply with study protocol and agree to sign an informed consent form.

Exclusion Criteria:

1. Having a history of topical or systematical hypersensitivity to indigo naturalis or its excipient (e.g. beeswax) in ointment
2. Undergoing phototherapy (e.g. UVB, PUVA) or systemic therapy (e.g. Immunosuppressive agents) within 30 days.
3. Having used topical therapy (e.g. topical corticosteroids) for dermatitis within 7 days before the first application of the study medication.
4. Having a significant concurrent disease, such as: significant abnormalities in hematology, severe uncontrolled metabolic syndrome (e.g., hypertension, diabetes mellitus, metabolic arthritis, hyperthyroidism), psychiatric disease, cancer or AIDS.
5. Having abnormal liver or renal function (AST/ALT >3 x ULN, creatinine >2.0 mg/dl).
6. Women who are lactating, pregnant or preparing to be pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Indigo naturalis ointment; Form: ointment; Dose: each gram of ointment contains 200µg of indirubin; Dosing schedule: apply 0.5g of ointment per 10 x 10 dermatitis lesion twice daily	Drug: Indigo naturalis ointment; Every 10 x 10 cm area of lesion requires 0.5 g of ointment, applied twice daily (morning and evening, separated by approximately 12±2 hours) for 6 weeks.; Other Names: Lindioil ointment
PLACEBO_COMPARATOR: Placebo; Form: ointment; Dose: vehicle; Dosing schedule: apply 0.5g of ointment per 10 x 10 dermatitis lesion twice daily	Drug: Placebo; Every 10 x 10 cm area of lesion requires 0.5 g of ointment, applied twice daily (morning and evening, separated by approximately 12±2 hours) for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in Eczema Area Severity Index (EASI) scores from baseline to week 6	The Eczema Area and Severity Index (EASI) is used to measure the disease severity of erythema, infiltration/papulation, excoriation, and lichenification each on a scale of 0 to 3 (none to severe) as well as the percentage of disease area on a scale of 0 to 6 for the head ⁄ neck, upper limb, trunk and lower limb body regions. Each body region score is calculated by multiplying the disease severity score by the disease area score and by the multiplier. The scores are summed to give the total EASI score, ranging from 0 to a maximum 72. The mean percentage change in EASI = (EASI baseline-EASI post-treat) / EASI baseline x 100%	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects who have achieved EASI-50, EASI-75, and EASI-90 after 6 weeks of treatment	It is defined as at least 50%, 75%, and 90% reduction in EASI score relative to the baseline.	6 weeks
Proportion of subjects with a change in Investigator's Global Assessment (IGA, range 0-5) from baseline to week 6.	Proportion of subjects with an IGA score of 0 (clear) or 1 (almost clear) at week 6.; Proportion of subjects with ≥ 2 point improvement in IGA at week 6.	6 weeks
The mean percentage change in Total Body Surface Area involved with AD (BSA, range 0%-100%) from baseline to week 6.	BSA is total Body Surface Area involved, ranging from 0% (none) to 100% (total body surface involved)	6 weeks
The mean change in pruritus score (10-cm visual analogue scale) from baseline to week 6.	Visual Analogue Scale (VAS) for pruritus severity rates from 0 (no itching) to 10 (very severe itching)	6 weeks
Clinical-immunological correlation between the treatment outcome and the changes in the level of immunoglobin E (IgE), cytokines, eosinophil count, and C-reactive protein (CRP) in the peripheral blood from baseline to week 6.	Measuring the correlations of treatment by EASI score and BSA, with the changes in IgE, eosinophils, cytokines (IL-1β, IL-6, TNF-α…) from baseline to week 6.	6 weeks
The mean change in Dermatology Life Quality Index (DLQI)from baseline to week 6	The DLQI is a self-administered 10-item questionnaire, ranges from 0 (best) to 30 (worst); the higher the score, the more quality of life is impaired. For subjects from age 6 to age 16, children's DLQI (CDLQI) will used.	6 weeks
Physician's Global Assessment (PGA ) at week 6.	0 = Symptoms cleared or excellent improvement of 90-100%; 1 = Marked improvement of 75-89%; 2 = Moderate improvement of 50-74%; 3 = Slight improvement of 3049%; 4 = No appreciable improvement of 029%; 5 = Worsening of the condition	6 weeks
Subject's Global Assessment (SGA) at week 6.	0 = Symptoms cleared or excellent improvement of 90-100%; 1 = Marked improvement of 75-89%; 2 = Moderate improvement of 50-74%; 3 = Slight improvement of 3049%; 4 = No appreciable improvement of 029%; 5 = Worsening of the condition	6 weeks

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Ministry of Science and Technology, Taiwan

Publications and helpful links

General Publications

• Lin YK, Chang SH, Yang CY, See LC, Lee BH, Shih IH. Efficacy and safety of indigo naturalis ointment in Treating Atopic Dermatitis: A randomized clinical trial. J Ethnopharmacol. 2020 Mar 25;250:112477. doi: 10.1016/j.jep.2019.112477. Epub 2019 Dec 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2015
• Primary Completion (ACTUAL): January 1, 2017
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: December 28, 2015
• First Submitted That Met QC Criteria: January 29, 2016
• First Posted (ESTIMATE): February 1, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 13, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Atopic Dermatitis; TCM; Indigo Naturalis
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: MOST 104-2325-B-182A-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO