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Indigo Naturalis in Treating Atopic Dermatitis Topically

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02669888
Recruitment Status : Completed
First Posted : February 1, 2016
Last Update Posted : February 14, 2017
Sponsor:
Collaborator:
Ministry of Science and Technology, Taiwan
Information provided by (Responsible Party):
Chang Gung Memorial Hospital

Tracking Information
First Submitted Date  ICMJE December 28, 2015
First Posted Date  ICMJE February 1, 2016
Last Update Posted Date February 14, 2017
Actual Study Start Date  ICMJE October 2015
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2017)
Percentage change in Eczema Area Severity Index (EASI) scores from baseline to week 6 [ Time Frame: 6 weeks ]
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%
Original Primary Outcome Measures  ICMJE
 (submitted: January 29, 2016)
The mean percentage change in the Eczema Area Severity Index (EASI) scores (range 0-72) from baseline to week 6 [ Time Frame: 6 weeks ]
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. The EASI is determined by multiplying the disease severity score by the disease area score and then multiplied by a factor of 0.1 for head/neck, 0.2 for upper limbs, 0.3 for trunk and 0.4 for lower limbs. The scores are summed to determine the total EASI score, ranging from 0 to a maximum 72. The mean percentage change in EASI = (EASIbaseline-EASIpost-treat) / EASIbaseline x 100%
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2017)
  • Proportion of subjects who have achieved EASI-50, EASI-75, and EASI-90 after 6 weeks of treatment [ Time Frame: 6 weeks ]
    It is defined as at least 50%, 75%, and 90% reduction in EASI score relative to the baseline.
  • Proportion of subjects with a change in Investigator's Global Assessment (IGA, range 0-5) from baseline to week 6. [ Time Frame: 6 weeks ]
    1. Proportion of subjects with an IGA score of 0 (clear) or 1 (almost clear) at week 6.
    2. Proportion of subjects with ≥ 2 point improvement in IGA at week 6.
  • The mean percentage change in Total Body Surface Area involved with AD (BSA, range 0%-100%) from baseline to week 6. [ Time Frame: 6 weeks ]
    BSA is total Body Surface Area involved, ranging from 0% (none) to 100% (total body surface involved)
  • The mean change in pruritus score (10-cm visual analogue scale) from baseline to week 6. [ Time Frame: 6 weeks ]
    Visual Analogue Scale (VAS) for pruritus severity rates from 0 (no itching) to 10 (very severe itching)
  • 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. [ Time Frame: 6 weeks ]
    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.
  • The mean change in Dermatology Life Quality Index (DLQI)from baseline to week 6 [ Time Frame: 6 weeks ]
    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.
  • Physician's Global Assessment (PGA ) at week 6. [ Time Frame: 6 weeks ]
    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
  • Subject's Global Assessment (SGA) at week 6. [ Time Frame: 6 weeks ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2016)
  • Percentage of subjects with change in Investigator's Global Assessment (IGA) [ Time Frame: 6 weeks ]
    1. Percentage of subjects with IGA scores improved, maintained, or worsened at week 6.
    2. Percentage of subjects with IGA score of clear (0) or almost clear (1) at week 6.
    IGA score is a 6-point scale, ranging from 0 (clear) to 5 (very severe disease)
  • The mean change of improvement in the total Body Surface Area involved (BSA) [ Time Frame: 6 weeks ]
    BSA is total Body Surface Area involved, ranging from 0% (none) to 100% (total body surface involved)
  • The mean percentage change in scores for the severity of pruritus [ Time Frame: 6 weeks ]
    Visual Analogue Scale (VAS) for pruritus severity rates from 0 (no itching) to 10 (very severe itching)
  • Clincal-immunological correlation of treatment outcome in patients with atopic dermatitis CRP IgE Eosinophils Cytokines (IL-1β, IL-6, TNF-α…) [ Time Frame: 6 weeks ]
    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.
  • The mean change of in the Dermatology Life Quality Index (DLQI) and Children's DLQI (CDLQI) [ Time Frame: 6 weeks ]
    The DLQI is a self-administered 10-item questionnaire, calculated by summing the scores of each question resulting in 0 to 30. 0-1 = no effect at all on patient's life; 2-5 = small effect on patient's life; 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life; 21-30 = extremely large effect on patient's life
  • The Overall Assessment including Physician's and Subject's Global Assessment (PGA and SGA, respectively) [ Time Frame: 6 weeks ]
    PGA and SGA are on a 6-point scale, ranging from 0 to 5: 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 30-49%
    4. = No appreciable improvement of 0-29%
    5. = Worsening of the condition
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Indigo Naturalis in Treating Atopic Dermatitis Topically
Official Title  ICMJE Efficacy and Safety of Topical Indigo Naturalis in Treating Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial
Brief Summary

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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Atopic Dermatitis
Intervention  ICMJE
  • 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 Name: Lindioil ointment
  • 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.
Study Arms  ICMJE
  • Experimental: Indigo naturalis ointment
    1. Form: ointment
    2. Dose: each gram of ointment contains 200µg of indirubin
    3. Dosing schedule: apply 0.5g of ointment per 10 x 10 dermatitis lesion twice daily
    Intervention: Drug: Indigo naturalis ointment
  • Placebo Comparator: Placebo
    1. Form: ointment
    2. Dose: vehicle
    3. Dosing schedule: apply 0.5g of ointment per 10 x 10 dermatitis lesion twice daily
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 13, 2017)
48
Original Estimated Enrollment  ICMJE
 (submitted: January 29, 2016)
112
Actual Study Completion Date  ICMJE February 2017
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02669888
Other Study ID Numbers  ICMJE MOST 104-2325-B-182A-005
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Chang Gung Memorial Hospital
Study Sponsor  ICMJE Chang Gung Memorial Hospital
Collaborators  ICMJE Ministry of Science and Technology, Taiwan
Investigators  ICMJE
Principal Investigator: Yin-Ku Lin, MD., PhD. Chang Gung Memorial Hospital
PRS Account Chang Gung Memorial Hospital
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP