Clinical trial NCT03469232: Effectiveness and Clinical Mechanism of Huanglian-Jiedu Decoction in Patients With Intense-exuberant Stomach Fire Syndrome
Official title: Effectiveness and Clinical Mechanism of Huanglian-Jiedu Decoction in Patients With Intense-exuberant Stomach Fire Syndrome (Acute Pericoronitis, Minor Recurrent Aphthous Stomatitis and Recurrent Herpes Simplex Labialis)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Intense-exuberant Stomach Fire Syndrom
Acute Pericoronitis
Recurrent Aphthous Stomatitis
Recurrent Herpes Simplex Labialis
Lead sponsor: China Academy of Chinese Medical Sciences
Sponsor class: OTHER
First posted: 2018-03-19
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical research focus on evaluating the effectiveness of Huanglian-Jiedu Decoction in patients with intense-exuberant stomach fire syndrome (one of the common TCM syndrome)of acute pericoronitis,minor recurrent aphthous stomatitis and recurrent herpes simplex labialis,meanwhile, exploring the pharmacological mechanism and potential biomarkers of this traditional formula.

Detailed description: Huanglian-Jiedu Decoction, as a traditional Chinese medicine formula，includes 4 kinds of Chinese herbs as following: Huanglian (Rhizoma Coptidis), Huangbo (Cortex Phellodendri), Huangqin (Scutellaria baicalensis) and Zhizi (Scutellaria baicalensis). Huanglian-Jiedu Decoction has been recorded to be effective in many diseases that belong to the syndrome of intense-exuberant stomach fire from thousands years of clinical practice, just like acute pericoronitis, minor recurrent aphthous stomatitis and recurrent herpes simplex labialis,etc. While its clinical pharmacological mechanism has not been clearly illustrated. In this study, the investigators focus on evaluating the effectiveness of Huanglian-Jiedu Decoction in patients with intense-exuberant stomach fire syndrome (including three disease: acute pericoronitis, minor recurrent aphthous stomatitis and recurrent herpes simplex labialis), and exploring the pharmacological mechanism and potential biomarkers of this traditional formula.

Eligibility criteria: Inclusion Criteria:

* General inclusion criteria:

  1. Female or male patients.
  2. Age: 18 - 60 years.
  3. Meeting the diagnostic criteria of Intense-Exuberant Stomach Fire Syndrome according to the traditional Chinese medicine.
  4. Patient is willing to participate voluntarily and to sign a written patient informed consent.
* Disease-specific inclusion criteria for patients with acute pericoronitis:

  1. Patients with clinical diagnosis of acute pericoronitis and without treatment before the study began.
* Disease-specific inclusion criteria for patients with minor recurrent aphthous stomatitis:

  1. Patients with clinical diagnosis of minor recurrent aphthous stomatitis(MiRAS).
  2. A history of MiRAS for more than 6 months and an expectation that the ulcers normally take 5 or more days to resolve without treatment.
  3. Ulcer occurred less than 48h hours' duration without treatment.
* Disease-specific inclusion criteria for recurrent herpes simplex labialis

  1. Patients with clinical diagnosis of recurrent herpes simplex labialis.
  2. History of recurrent herpes labialis averaging 1 or more episodes per year.
  3. Onset of prodrome, erythema or vesicle within 48 hours without treatment.

Exclusion Criteria:

* General exclusion criteria:

  1. Patients with severe cardiac dysfunction on the grade of heart function over Ⅲ grade and/or liver function impairment with the value of ALT over 1.5-fold of normal value and/or renal dysfunction with the value over 133μmol/L.
  2. Patients who have serious, unstable, or clinically significant medical or psychological conditions, which, in the opinion of the investigator(s), would compromise the subject's participation in the study (including but not limited to arrhythmia, uncontrolled hypertension, diabetes, hepatitis, kidney failure, AIDS, cancer, etc.
  3. Women during pregnancy, lactation , breastfeeding or having child bearing potential without use an adequate method of birth control.
  4. Patients who known allergy to the study drug or the Huanglian (Rhizoma Coptidis), Huangbo (Cortex Phellodendri), Huangqin (Scutellaria baicalensis) and Zhizi (Scutellaria baicalensis ( Patients who are insufficiency of the spleen-yang according to the TCM should be exclude ).
  5. Patients participating in or having participated in other clinical studies in the 3 months prior to this clinical trial.
  6. Patients who are considered unreliable as to medication compliance or adherence to scheduled appointments.
* Disease-specific exclusion criteria for acute pericoronitis:

  1. Patients who smoked at least 20 cigarettes per day（heavy smokers）.
  2. Patients with fascial space infection of maxillofacial region or/and chronic periodontitis.
  3. Patients with periodontal disease in the region of the acute pericoronitis.
  4. Patients who had systemic administration of antibiotics within the past 4 weeks
* Disease-specific exclusion criteria for minor recurrent aphthous stomatitis(MiRAS):

  1. Patients with history of drug abuse within the past 6 months.
  2. Patients who smoked at least 20 cigarettes per day（heavy smokers）.
  3. Patients with ulcers as a manifestation of a systemic disease process such as ulcerative colitis, Behcet's syndrome, Reiter' s syndrome or immune deficiency.
  4. Patients who had systemic administration of antibiotics within the past 4 weeks or/ and had treatment with systemic steroid or immunomodulatory within 3 month before the study entry.
  5. Patients who had orthodontic braces or retainer that might contact with the ulcer.
* Disease-specific exclusion criteria for recurrent herpes simplex labialis:

  1. Patients with fever \> 38.5℃, and / or blood WBC\>11.0x109/L, and / or neutrophil \>85%.
  2. Patients who had systemic administration of antibiotics within the past 4 weeks or/ and had treatment with immunomodulatory within 3 month before the study entry.

Primary outcomes:
measure: Change from baseline in the Intense-Exuberant Stomach Fire Syndrome scores
timeFrame: Day 0,Day 3,Day 5
Secondary outcomes:
measure: Change from baseline of each symptom in Intense-Exuberant Stomach Fire Syndrome scores
timeFrame: Day 0,Day 3,Day 5
measure: The proportion of patients whose Intense-Exuberant Stomach Fire Syndrome were disappeared
timeFrame: Day 0,Day 5
measure: The proportion of patients who gain 50% reduction of Intense-Exuberant Stomach Fire Syndrome scores
timeFrame: Day 0,Day 5
measure: Change from baseline on toothache based on visual analogue scale(VAS)for acute pericoronitis
timeFrame: Day 0,Day 1,Day 2,Day 3,Day 4,Day 5
measure: Change from baseline on maximum mouth opening (MMO) for acute pericoronitis
timeFrame: Day 0,Day 3,Day 5
measure: Number of patients with trismu for acute pericoronitis
timeFrame: Day 0,Day 3,Day 5
measure: Change from baseline on OHIP-14 measures for acute pericoronitis
timeFrame: Day 0,Day 3,Day 5
measure: Change from baseline of VAS on the pain of ulcer for minor recurrent aphthous stomatitis
timeFrame: Day 0,Day 1,Day 2,Day 3,Day 4,Day 5
measure: The proportion of patients with ulcer healing for minor recurrent aphthous stomatitis
timeFrame: Day 0,Day 3,Day 5
measure: The sizes of ulcer for minor recurrent aphthous stomatitis
timeFrame: Day 0,Day 3,Day 5
measure: The number of days that the lesion was present (until loss of crust)for recurrent herpes simplex labialis
timeFrame: From the date of lesion or premonitory symptom present until the date of crust lose, which up to 28 days.
measure: The proportion of patients with lesion healing for recurrent herpes simplex labialis
timeFrame: Day 3,Day 5
measure: Change from baseline of VAS on the pain of lesions for recurrent herpes simplex labialis
timeFrame: Day 0,Day 1,Day 2,Day 3,Day 4,Day 5
Other outcomes:
measure: High-sensitivity C-reactive protein（hs-CRP）
timeFrame: Day 0,Day 5
measure: Evaluation of inflammatory cytokines
timeFrame: Day 0,Day 5
measure: Activity of sirtuins (SIRTs)
timeFrame: Day 0,Day 5
measure: GSH/GSSG ratios in plasma
timeFrame: Day 0,Day 5
measure: Evaluation of oxidative stress parameters：SOD
timeFrame: Day 0,Day 5
measure: Evaluation of oxidative stress parameters：MDA
timeFrame: Day 0,Day 5
measure: Pyruvate Acid / Uric Acid ratios in plasma
timeFrame: Day 0,Day 5
measure: Mass Spectrometry analyses for urine sample
timeFrame: Day 0,Day 5
measure: Proteomic analyses for blood sample
timeFrame: Day 0,Day 5
measure: Proteomic analyses for urine sample
timeFrame: Day 0,Day 5
Locations:
city: Beijing
country: China
facility: Third affiliated hospital of Beijing University of traditional Chinese medicine
state: Beijing
city: Beijing
country: China
facility: Dongfang Hospital Affiliated to Beijing University of traditional Chinese medicine
state: Beijing
city: Chengdu
country: China
facility: Affiliated Hospital to Chengdu University of traditional Chinese medicine
state: Sichuan
Study officials:
affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences
name: Zhong Wang
role: PRINCIPAL_INVESTIGATOR
References: