AzTrials
AzTrials

Atopic DermatitisPhase 2NCT03614221

Comparison of Lindioil (Indigo Naturalis Oil Extract) Ointment to Protopic® Ointment 0.1% in Treating Atopic Dermatitis

A Phase 2 study testing Lindioil ointment and Protopic ointment 0.1% in people with Atopic Dermatitis, run by Chang Gung Memorial Hospital at 2 sites in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The aims of this study are: 1. Compare the efficacy of Lindioil ointment and Protopic® ointment in treating atopic dermatitis. 2. Compare the safety of Lindioil ointment and Protopic® ointment in treating atopic dermatitis. 3. Read more about this study

Who is it for?
Ages 16 to 65 years
Conditions the study is for
Atopic Dermatitis
What is being tested?
Lindioil ointment and Protopic ointment 0.1%
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
2 sitesTaiwan
Study dates
3 Jun 2019to 6 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Between 16 and 65 years old, female or male.
  • Chronic or sub-acute atopic dermatitis fulfilling the United Kingdom (UK) diagnostic criteria of atopic dermatitis.
  • Atopic dermatitis involving 3-40% of BSA at screening and baseline.
  • An IGA score of 2 (mild) to 4 (severe) at screening and baseline.
  • Not supposed to or unwilling to use corticosteroids.
  • Female patients of child-bearing age agree to use effective birth control measures approved by the investigator.
  • Agree to avoid natural and artificial sunlight over-exposure during the study.
  • Willing to comply with study protocol and agree to sign an informed consent form

Who cannot join

  • Acute atopic dermatitis or concurrence of viral or bacterial infection on dermatitis lesion(s).
  • A history of topical or systematic hypersensitivity to indigo naturalis, tacrolimus, or the excipient(s) in the ointment(s).
  • Having received systemic therapy (e.g. immunosuppressive agents) within 14 days, or phototherapy (e.g.
  • ultraviolet B (UVB), psoralen and ultraviolet A (PUVA)) within 42 days before the first application of the study medication.
  • Having used topical therapy (e.g. corticosteroids) for dermatitis within 4 days before the first application of the study medication.
  • Having a significant concurrent disease such as severe uncontrolled chronic disease (e.g., hypertension, diabetes mellitus, metabolic arthritis, hyperthyroidism), psychiatric disease, cancer or AIDS.
  • Having significant abnormal liver or renal function (Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) >3 x upper limit of normal (ULN), creatinine >2.0 mg/dl) or clinically significant abnormal hematological lab result, according to investigator's judgment, on the safety lab test to be performed within 30 days before the baseline visit.
  • Women who are lactating, pregnant or planning to be pregnant during the study.

Trial locations and contacts

2 sites in 1 country.

Taiwan2 sites

  • Taipei Chang Gung Memorial Hospital

    Taipei, 10507

  • Linkou Chang Gung Memorial Hospital

    Taoyuan, 33305

Other trials in Taiwan

About this study

Official title: Comparison of the Efficacy and Safety of Lindioil (Indigo Naturalis Oil Extract) Ointment to Protopic® (Tacrolimus 0.1%) Ointment in Treating Atopic Dermatitis: A Randomized, Evaluator-blind, Crossover, Active-Controlled Trial

The aims of this study are:

  1. Compare the efficacy of Lindioil ointment and Protopic® ointment in treating atopic dermatitis.
  2. Compare the safety of Lindioil ointment and Protopic® ointment in treating atopic dermatitis.
  3. Compare the time to relapse after ceasing of treatment of Lindioil ointment and Protopic® ointment.
  4. Compare the change of skin microbiome before and after Lindioil ointment and Protopic® ointment treatment.
Read the detailed description

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by itchiness. Topical corticosteroids are typically used to treat AD. However, many patients have concerns about the safety of long-term use, and seek alternative therapies 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. The investigate also found that the results of indigo naturalis ointment treatment in other trial were comparable to the results of calcineurin inhibitor (such as Tacrolimus) treatment, and would like to verify this assertion. The aim of this study is to compare the efficacy of Lindioil ointment with that of Protopic® (Tacrolimus ointment 0.1%) in treating AD.

Being tested
Lindioil ointment, Protopic ointment 0.1%
Keywords
Atopic Dermatitis, Indigo naturalis, Tacrolimus
Medical subject headings
Dermatitis, Atopic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lindioil ointmentDrug

    Also called Indigo naturalis oil extract ointment

    Each gram contains 200µg of indirubin. Apply 0.5 g of ointment per 10 cm x 10 cm of affected skin areas twice daily for 6 weeks.

  • Protopic ointment 0.1%Drug

    Also called Tacrolimus ointment 0.1%

    Each gram contains (w/w) 0.1% of tacrolimus. Apply 0.1 g of ointment per 10 cm x 10 cm of affected skin areas twice daily for 6 weeks.

Study groups in NCT03614221
Study groupRoleWhat they receive
LindioilExperimentalLindioil ointment is applied twice daily for 6 weeks, followed by a washout period of 4 days to 8 weeks depending on the results of the first treatment period and the amount of time it takes the participant to relapse to IGA ≥ 2 and less than 1-point of change from baseline1ST IGA. If relapse to IGA ≥ 2 and less than 1-point of change from baseline1ST IGA is achieved, the patient is using Protopic ointment 0.1% twice daily for another 6 weeks. If the criteria for entering the 2nd treatment are not achievable after 8-week of ceasing 1st treatment, the subject will be followed up for another 6 weeks to the end of the study
Receives: Drug: Lindioil ointment; Drug: Protopic ointment 0.1%
ProtopicActive comparatorProtopic ointment 0.1% is applied twice daily for 6 weeks, followed by a washout period of 4 days to 8 weeks depending on the results of the first treatment period and the amount of time it takes the participant to relapse to IGA ≥ 2 and less than 1-point of change from baseline1ST IGA. If relapse to IGA ≥ 2 and less than 1-point of change from baseline1ST IGA is achieved, the patient is using Lindioil ointment twice daily for another 6 weeks. If the criteria for entering the 2nd treatment are not achievable after 8-week of ceasing 1st treatment, the subject will be followed up for another 6 weeks to the end of the study
Receives: Drug: Lindioil ointment; Drug: Protopic ointment 0.1%

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The mean percentage change from baseline to the end of week 6 of Eczema Area Severity Index (EASI) scores (range 0-72), for each of the two 6-week treatment periods.

    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 4 body regions: head ⁄ neck, upper limbs, trunk and lower limbs. Each body region score is calculated by multiplying the disease severity score by the disease area score and by the multiplier, 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 give the total EASI score, ranging from 0 to a maximum 72.

    Measured: 6-week, 12-week (the end of the second treatment period)

Secondary outcomes (9)

  1. Proportion of participants who have achieved a 50%, 75% and 90% improvement in EASI scores (EASI-50, EASI-75 and EASI-90, respectively) at the end of week 6 of each treatment period.

    It is defined as at least 50%, 75%, and 90% reduction in EASI score compare to the baseline.

    Measured: 6-week, 12-week (the end of the second treatment period)

  2. Proportion of participants with an Investigator's Global Assessment (IGA, 0-5) score of 0 (clear) or 1 (almost clear) at the end of week 6 of each treatment period.

    Investigator's Global Assessment (IGA) is a 6-points scale ranging from 0 (cleared) to 5 (Very severe) for evaluation of the severity of atopic dermatitis.

    Measured: 6-week, 12-week (the end of the second treatment period)

  3. The mean percentage change from baseline to the end of week 6 of the Body Surface Area (BSA, range 0%-100%) affected by AD, for each of the two 6-week treatment periods.

    BSA is total body surface area affected by atopic dermatitis, ranging from 0% (none) to 100% (total body surface affected).

    Measured: 6-week, 12-week (the end of the second treatment period)

  4. Number of days until relapse to IGA ≥ 2, after ceasing treatment, for subjects who achieved IGA 0 or 1 at the end of week 6 of each treatment period.

    Length of relapse free days after ceasing treatment

    Measured: 6-week, 12-week (the end of the second treatment period)

  5. The change from baseline to the end of week 6 of Numeric Rating Scale for pruritus (NRS, 0-10), for each of the two 6-week treatment periods.

    Numeric Rating Scale for pruritus (NRS) is a tool to evaluate itching intensity from 0 (no itch) to 10 (most imaginable itch)

    Measured: 6-week, 12-week (the end of the second treatment period)

  6. The change from baseline to the end of week 6 of Dermatology Life Quality Index (DLQI) for each of the two 6-week treatment periods.

    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.

    Measured: 6-week, 12-week (the end of the second treatment period)

  7. Proportion of participants with a Subject's Global Assessment (SGA, 0-6) score of 0 (much better) or 1 (better) at the end of week 6 of each treatment period.

    Subject's Global Assessment (SGA) is a self-evaluated the change from baseline of their AD condition as 'much better' (0), 'better' (1) , 'slightly better' (2), 'same' (3), 'slightly worse' (4), 'worse' (5) or 'much worse' (6).

    Measured: 6-week, 12-week (the end of the second treatment period)

  8. The participants' preference of using Lindioil ointment and Protopic® ointment treatment.

    Patients who completed the second treatment period will answer which ointment with better efficacy, which with more adverse events, and the adverse event bothering them most.

    Measured: 13 weeks (the end of the second treatment period)

  9. The change of skin microbiome before and after Lindioil ointment and Protopic® ointment treatment.

    Skin swabs of lesion and non-lesion will be obtained from patient before and after study treatment to analyze skin microbiome.

    Measured: 6-week, 12-week (the end of the second treatment period)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2018
  2. Study start3 Jun 2019
  3. Primary completion1 Dec 2021
  4. Study completion6 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03614221
Sponsor's protocol ID
MOST107-2320-B-182A-002 -MY3
Status last verified
Feb 2023
First submitted
31 Jul 2018
Last updated
10 Feb 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Al-Daraji WI, Grant KR, Ryan K, Saxton A, Reynolds NJ. Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of calcineurin/NFAT activation in human keratinocytes by cyclosporin A. J Invest Dermatol. 2002 May;118(5):779-88. doi: 10.1046/j.1523-1747.2002.01709.x.

    PubMed 11982754

  • Caproni M, Torchia D, Antiga E, Terranova M, Volpi W, del Bianco E, D'Agata A, Fabbri P. The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study. Br J Dermatol. 2007 Feb;156(2):312-9. doi: 10.1111/j.1365-2133.2006.07609.x.

    PubMed 17223872

  • Simon D, Vassina E, Yousefi S, Kozlowski E, Braathen LR, Simon HU. Reduced dermal infiltration of cytokine-expressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment. J Allergy Clin Immunol. 2004 Oct;114(4):887-95. doi: 10.1016/j.jaci.2004.05.066.

    PubMed 15480330

  • Furukawa H, Nakamura K, Zheng X, Tojo M, Oyama N, Akiba H, Nishibu A, Kaneko F, Tsunemi Y, Saeki H, Tamaki K. Enhanced TARC production by dust-mite allergens and its modulation by immunosuppressive drugs in PBMCs from patients with atopic dermatitis. J Dermatol Sci. 2004 Jun;35(1):35-42. doi: 10.1016/j.jdermsci.2004.02.008.

    PubMed 15194145

  • Chang KT, Lin HY, Kuo CH, Hung CH. Tacrolimus suppresses atopic dermatitis-associated cytokines and chemokines in monocytes. J Microbiol Immunol Infect. 2016 Jun;49(3):409-16. doi: 10.1016/j.jmii.2014.07.006. Epub 2014 Oct 12.

    PubMed 25315214

  • Vukmanovic-Stejic M, McQuaid A, Birch KE, Reed JR, Macgregor C, Rustin MH, Akbar AN. Relative impact of CD4+CD25+ regulatory T cells and tacrolimus on inhibition of T-cell proliferation in patients with atopic dermatitis. Br J Dermatol. 2005 Oct;153(4):750-7. doi: 10.1111/j.1365-2133.2005.06675.x.

    PubMed 16181456

  • Lan CC, Kao YH, Huang SM, Yu HS, Chen GS. FK506 independently upregulates transforming growth factor beta and downregulates inducible nitric oxide synthase in cultured human keratinocytes: possible mechanisms of how tacrolimus ointment interacts with atopic skin. Br J Dermatol. 2004 Sep;151(3):679-84. doi: 10.1111/j.1365-2133.2004.06109.x.

    PubMed 15377358

  • Paller AS, Lebwohl M, Fleischer AB Jr, Antaya R, Langley RG, Kirsner RS, Blum RR, Rico MJ, Jaracz E, Crowe A, Linowski GJ; US/Canada Tacrolimus Ointment Study Group. Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, comparative studies. J Am Acad Dermatol. 2005 May;52(5):810-22. doi: 10.1016/j.jaad.2004.12.038.

    PubMed 15858471

  • Breneman D, Fleischer AB Jr, Abramovits W, Zeichner J, Gold MH, Kirsner RS, Shull TF, Crowe AW, Jaracz E, Hanifin JM; Tacrolimus Ointment Study Group. Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. J Am Acad Dermatol. 2008 Jun;58(6):990-9. doi: 10.1016/j.jaad.2008.02.008. Epub 2008 Mar 21.

    PubMed 18359127

  • Lin YK, Chang CJ, Chang YC, Wong WR, Chang SC, Pang JH. Clinical assessment of patients with recalcitrant psoriasis in a randomized, observer-blind, vehicle-controlled trial using indigo naturalis. Arch Dermatol. 2008 Nov;144(11):1457-64. doi: 10.1001/archderm.144.11.1457.

    PubMed 19015420

  • Lin YK, Chang YC, Hui RC, See LC, Chang CJ, Yang CH, Huang YH. A Chinese Herb, Indigo Naturalis, Extracted in Oil (Lindioil) Used Topically to Treat Psoriatic Nails: A Randomized Clinical Trial. JAMA Dermatol. 2015 Jun;151(6):672-4. doi: 10.1001/jamadermatol.2014.5460. No abstract available.

    PubMed 25738921

  • Lin YK, See LC, Huang YH, Chang YC, Tsou TC, Lin TY, Lin NL. Efficacy and safety of Indigo naturalis extract in oil (Lindioil) in treating nail psoriasis: a randomized, observer-blind, vehicle-controlled trial. Phytomedicine. 2014 Jun 15;21(7):1015-20. doi: 10.1016/j.phymed.2014.02.013. Epub 2014 Mar 26.

    PubMed 24680615

  • Lin YK, See LC, Huang YH, Chi CC, Hui RC. Comparison of indirubin concentrations in indigo naturalis ointment for psoriasis treatment: a randomized, double-blind, dosage-controlled trial. Br J Dermatol. 2018 Jan;178(1):124-131. doi: 10.1111/bjd.15894. Epub 2017 Dec 14.

    PubMed 28815560

  • Hoessel R, Leclerc S, Endicott JA, Nobel ME, Lawrie A, Tunnah P, Leost M, Damiens E, Marie D, Marko D, Niederberger E, Tang W, Eisenbrand G, Meijer L. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat Cell Biol. 1999 May;1(1):60-7. doi: 10.1038/9035.

    PubMed 10559866

  • Marko D, Schatzle S, Friedel A, Genzlinger A, Zankl H, Meijer L, Eisenbrand G. Inhibition of cyclin-dependent kinase 1 (CDK1) by indirubin derivatives in human tumour cells. Br J Cancer. 2001 Jan;84(2):283-9. doi: 10.1054/bjoc.2000.1546.

    PubMed 11161389

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lindioil ointment and Protopic ointment 0.1% in people with Atopic Dermatitis, run by Chang Gung Memorial Hospital at 2 sites in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The mean percentage change from baseline to the end of week 6 of Eczema Area Severity Index (EASI) scores (range 0-72), for each of the two 6-week treatment periods. (time frame: 6-week, 12-week (the end of the second treatment period)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03614221, which also lists 30 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in