Mechanistic Study of Indigo Naturalis in Treating Psoriasis

NCT ID: NCT02088281

Last Updated: 2014-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2013-07-31

Brief Summary

The potential effect of indigo naturalis on the immune system is unknown. The investigators hypothesize that the therapeutic effect of indigo naturalis in psoriasis may involve inhibiting the activation of Th1 and Th17 cells that produce pro-inflammatory cytokines, thereby regulating the hyperplasia of epidermis induced by Th1/Th17 related cytokines.

Detailed Description

Psoriasis is a chronic inflammatory dermatosis induced by altered interactions between the immune system and skin and characterized by hyperplasia of the epidermis (acanthosis), infiltration of leukocytes into both the dermis and epidermis, and dilation and growth of blood vessels. Our previous studies have shown that topical application of indigo naturalis significantly improves psoriatic symptoms and demonstrated that the anti-psoriatic effects of indigo naturalis are mediated by promoting differentiation and inhibiting proliferation of epidermal keratinocytes. However, the potential effect of indigo naturalis on the immune system is unknown.

Currently, growing evidence demonstrates that activated T cells are the primary modulators in the pathogenesis of psoriasis and psoriasis is believed to be a mixed Th1/Th17 disease with strong IL-17 and interferon-γ (IFN-γ) signatures. The identification of elevated levels of IFN-γ, tumor necrosis factor (TNF-α), IL-12, IL-17 and IL 22 in cutaneous lesions and in the serum of psoriatic patients supports the theory that these Th1/Th17-related cytokines directly or indirectly act on keratinocytes leading to their activation and hyperproliferation. The investigators suppose the therapeutic effect of indigo naturalis in psoriasis may involve inhibiting the activation of Th1 and Th17 cells that produce pro-inflammatory cytokines, thereby regulating the hyperplasia of epidermis induced by Th1/Th17 related cytokines.

The aim of this study is:

1. To investigate whether the effect of indigo naturalis in improving psoriatic symptoms is associated with the function of Th1/Th17 cells expressing IFN-γ and IL-17 in peripheral blood of patients with psoriasis before and after therapy.

2. To investigate whether the effect of indigo naturalis in improving psoriatic symptoms is associated with the production of pro-inflammatory cytokines in peripheral blood of patients with psoriasis before and after therapy.

3. To investigate whether the effect of indigo naturalis in improving psoriatic symptoms is associated with histopathological change in psoriatic lesions and whether these pathological changes are different from the change in inflammatory and immune reactions in patients with psoriasis.

4. To investigate the effects of Th1/Th17-related cytokines and immunological factors in patients with indigo naturalis treatment on epidermal keratinocytes.

5. To detect the effect of indigo naturalis on the function of releasing cytokines (IFN-γ, IL-17, and IL-23, etc.) from monocytes in patients with psoriasis.

6. To analyze the concentration of indirubin in peripheral blood and to clarify whether the effect of indigo naturalis in improving psoriatic symptoms is: (A) a systemic effect that affects the metabolism and immune system through absorption and transdermal delivery into body. (B) a direct effect on the epidermal keratinocytes alone.

Conditions

Psoriasis Vulgaris

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Indigo naturalis extract in oil ointment

Indigo naturalis extract in oil ointment: each gram of ointment contains 200 μg±20 μg of indirubin.

Group Type: EXPERIMENTAL

Indigo naturalis extract in oil ointment

Intervention Type: DRUG

Apply 0.5 g of INEO ointment per 10 x 10 cm psoriasis lesion twice daily.

Interventions

Indigo naturalis extract in oil ointment

Apply 0.5 g of INEO ointment per 10 x 10 cm psoriasis lesion twice daily.

Intervention Type: DRUG

Other Intervention Names

INEO ointment

Eligibility Criteria

Inclusion Criteria

• Aged 20 - 65 years, men or women
• Diagnosed as plaque-type psoriasis by the dermatologist.
• Plaque psoriasis involving <20% of the body surface area (BSA) and the psoriasis area and severity index (PASI) <20
• If of child-bearing age, negative pregnancy test at screening, agreement to continue using birth control measures approved by the investigator for the duration of the study.
• Willingness to comply with study protocol and signed informed consent form.

Exclusion Criteria

• A history of topically or systematically sensitivity to indigo naturalis or any component in excipient.
• Systematic therapy for psoriasis within 4 weeks of baseline including Methotrexate (MTX), immunosuppressive agents (e.g. cyclosporine), retinoid (vitamin A derivatives), biologics (e.g. Etanercept, Alefacept, Infliximab), vitamin D3 analogs and phototherapy.
• Topical therapy for psoriasis within 2 weeks of baseline including tar, corticosteroid, vitamin D3 analogs, retinoid.
• Pustular or generalized erythrodermic psoriasis.
• With abnormal liver or renal function (e.g. liver cirrhosis, hepatitis B/C, renal failure, creatinine >2.0 mg/dL, AST/ALT >3 x ULN), clinically significant abnormalities in hematology, severe uncontrolled metabolic syndrome (e.g., hypertension, diabetes mellitus, metabolic arthritis, hyperthyroidism), psychiatric disease, cancer or AIDS.
• Women who are lactating, are pregnant or are planning to become pregnant.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Science and Technology Council, Taiwan

OTHER_GOV

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

YIn-Ku Lin, MD., PhD.

Role: PRINCIPAL_INVESTIGATOR

Department Traditional Chinese Medicine, Chang Gung Memorial Hospital at Keelung

Locations

Chang Gung Medical Foundation, Chang Gung University

Taoyuan District, , Taiwan

Countries

Taiwan

Other Identifiers

NSC 101-2320-B-182-021-MY3

Identifier Type: -

Identifier Source: org_study_id