Clinical trial NCT05295979: Chinese Medicine for Patients With Psoriasis
Official title: Development of a Novel Chinese Medicine Formula for the Treatment of Psoriasis: A Randomized, Double-blinded, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Psoriasis
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-03-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Psoriasis is an inflammatory skin disease with huge negative impact on the quality of life of the patients, and has an overall prevalence of 2% to 3% in the general population. Plaques psoriasis is the most common type of the disease and presents red, well demarcated, and silvery plaques mainly localized in the umbilical and lumbosacral area as well as in the elbows, knees, and scalp.

Currently, pharmacological treatments such as retinoids, corticosteroids, vitamin D analogs and biologics remain the main options for most psoriasis patients. However, side effect and high cost barred many ordinary psoriasis patients.

A Chinese medicine formula "Inflammatory skin disease formula (ISDF)" was prescribed by Prof. Lin for many years and observed to be effective in relieving atopic dermatitis and psoriasis patients' clinical manifestations.

In this study, subjects with psoriasis will be randomized into treatment group of "ISDF" or placebo group for 12 weeks.

Detailed description: Psoriasis is an inflammatory skin disease with huge negative impact on the quality of life of the patients, and has an overall prevalence of 2% to 3% in the general population. Plaques psoriasis is the most common type of the disease and presents red, well demarcated, and silvery plaques mainly localized in the umbilical and lumbosacral area as well as in the elbows, knees, and scalp. The major histological features of psoriasis include epidermal hyperplasia with aberrant keratinocyte differentiation, pronounced inflammatory cell infiltration and increased vascularization. Currently, pharmacological treatments such as retinoids, corticosteroids, and vitamin D analogs remain the main options for most psoriasis patients. However, the efficacy of conventional drugs is limited because of adverse side effects and the development of pharmacoresistance. Recently, biologics have become available for the treatment of acute and subacute plaque psoriasis with excellent response rate. However, the high costs involved with the biologics have barred many ordinary psoriasis patients from benefiting from this new class of anti-psoriatic medication. Natural products are valuable sources in novel drug development. Inflammatory skin disease formula (ISDF) is an empirical formula of the Principal Investigator (Prof. Zhi-Xiu Lin), a highly experienced Registered Chinese Medicine Practitioner and Chinese medicine dermatologist working at the School of Chinese Medicine, The Chinese University of Hong Kong. ISDF has been prescribed in clinic in Hong Kong for many years and observed to be effective in relieving atopic dermatitis and psoriasis patients' clinical manifestations. ISDF contains nine Chinese herbal medicines, including Rehmanniae Radix (Dihuang) 20.0 g, Paeoniae Radix Rubra (Chiyao) 10.0 g, Scutellariae Radix (Huangqin) 10.0 g, Phellodendri Cortex (Huangbai) 10.0 g, Forsythiae Fructus (Lianqiao) 12.0 g, Plantaginis Semen (Cheqianzi) 10.0 g, Vignae Semen (Chixiaodou) 10.0 g, Dictamni Cortex (Baixianpi) 10.0 g and Kochiae Fructus (Difuzi) 10.0 g. Among them, Rehmanniae Radix is frequently used for the treatment of psoriasis in Chinese medicine. Paeoniflorin, the major active ingredients of Paeoniae Radix Rubra, has been reported to inhibit imiquimod (IMQ)-induced psoriasis in mice by regulating Th17 cell response and cytokine secretion. Baicalin, the active components of Scutellariae Radix, was able to improve the psoriasis-like skin lesions induced by IMQ or 2,4-dinitrofluorobenzene (DNCB) in mice. Berberine, the main alkaloid of Phellodendri Cortex, could inhibit IMQ-induced psoriasis-like skin lesions and upregulation of CDC6 and p-STAT3 in mice.

Recent study demonstrated that ISDF (named SZF in the study) markedly decreased the epidermal thickening and infiltration of mast cells in the ears and dorsal skin of the DNCB-treated mice via inhibition of inflammation through inactivation of NF-κB p65 pathway. The ISDF was found to contain baicalin (4.92%, w/w), berberine (2.90%, w/w), paeoniflorin (0.26%, w/w) and phillyrin (0.10%, w/w). Recent preliminary data revealed that ISDF significantly improved the psoriatic-like symptoms and reduced the epidermal thickening in the dorsal skin of IMQ-stimulated mice via inhibition of the inflammation response. The results on its acute toxicity demonstrated that ISDF at up to the dose of 37.8 g/kg, which was the maximum tolerable dose of ISDF in mice, did not exert any overt toxicity. Based on these positive findings of pilot study, the investigators therefore hypothesize that ISDF is an effective herbal formula with anti-psoriatic effects. In Chinese medicine (CM) theory, psoriasis may be classified into different subtypes or "syndromes", including syndrome of wind-heat and blood heat, which is also known as blood heat syndrome or syndrome of wind-heat and blood dryness; syndrome of blood deficiency and wind-dryness; syndrome of blood stasis in the skin; and dampness-heat syndrome. Each of these syndromes represents a different pathogenesis in CM and corresponds to a different stage or manifestation of psoriasis. ISDF is composed of herbal medicines that can clear heat to cool the blood, clear heat and dry dampness, clear heat and drain dampness, disperse wind-heat, and is suitable for treating psoriasis with wind-heat, blood heat or dampness-heat. A randomized, double-blinded, placebo-controlled trial will be conducted to evaluate the efficacy of ISDF on psoriasis patients. Clinical evidence for the anti-psoriatic effects of ISDF, and is a necessary step towards developing this Chinese medicine formula into an anti-psoriatic pharmaceutical agent.

Eligibility criteria: Inclusion Criteria:

* Mild to moderate chronic plaque psoriasis (PASI score 3 to 12).
* Willingness to give informed consent.

Exclusion Criteria:

* Pustular or generalized erythrodermic psoriasis.
* Psoriatic arthritis with syndrome of spleen-kidney yang deficiency according to Chinese medicine theory.
* Systemic therapy for psoriasis 6 months prior to baseline.
* Use topical medications for psoriasis 14 days prior to baseline such as retinoids, corticosteroids, vitamin D analogues, tazarotene and tacrolimus.
* Has taken any antibiotics, probiotics and prebiotics 30 days prior to baseline.
* UV light therapy 30 days prior to baseline.
* Clinically significant laboratory abnormality in blood, liver or renal functions (≥1.5 times the upper limit of reference range).
* History of allergy to Chinese herbs.
* Unwillingness to comply with study protocol.
* Any other condition that in the opinion of the investigators could compromise the study.

Primary outcomes:
measure: Psoriasis Area and Severity Index (PASI)
timeFrame: Week 12
measure: Static Physician Global Assessment score (sPGA)
timeFrame: Week 12
Secondary outcomes:
measure: Psoriasis Area and Severity Index (PASI)
timeFrame: Week 6
measure: Psoriasis Area and Severity Index (PASI)
timeFrame: Week 18
measure: Static Physician Global Assessment score (sPGA)
timeFrame: Week 6
measure: Static Physician Global Assessment score (sPGA)
timeFrame: Week 18
measure: Impact of Psoriasis Questionnaire (IPSO)
timeFrame: Week 12
measure: Short Form 36 survey (SF36)
timeFrame: Week 12
measure: Use of rescue therapy
timeFrame: Up to Week 18
measure: Adverse events
timeFrame: Up to Week 18
measure: Serum markers (IL-17A, IL-22, IL-23, CRP and BD-2)
timeFrame: Week 12
measure: Oral and Gut microbiota composition in saliva and stools
timeFrame: Week 12
measure: Psoriasis Itch Visual Analog Scale (Itch VAS)
timeFrame: Week 12
measure: Psoriasis-involved body surface area (BSA)
timeFrame: Week 6
measure: Psoriasis-involved body surface area (BSA)
timeFrame: Week 12
measure: Psoriasis-involved body surface area (BSA)
timeFrame: Week 18
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Hong Kong Institute of Integrative Medicine
Study officials:
affiliation: Hong Kong Institute of Integrative Medicine
name: Zhixiu Lin, PhD
role: PRINCIPAL_INVESTIGATOR
References: