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临床试验/NCT03562429
NCT03562429Unknown2 期

The Efficacy of TGF for Treating Osteoarthritis of the Knee: A Randomized Double-blind Controlled Trial

China Medical University Hospital0 个研究点目标入组 180 人开始时间: 2018年8月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
2 期
入组人数
180
主要终点
Visual Analogue Scale for pain

研究概览

简要总结

This study is to evaluate the efficacy of herbal formula TGF treating knee joint osteoarthritis(KOA) and its biochemical mechanism. The study design is a parallel randomized, placebo-controlled, double-blind clinical trial includes 180 patients with KOA. The patients are random allocated into study group(taking TGF) and control group(taking 1/20 TGF). After the 12 weeks treatment course, another 4 weeks is to follow-up the condition without medication. Assessments will be performed before and after treatment and the end of follow-up period.

The inclusion criteria are (1) age between 50~75 years old, (2) diagnosis of osteoarthritis: The Clinical/Radiographic classification criteria of American College of Rheumatology, American College of Rheumatology, (3) chronic knee pain over 3 months. The exclusion criteria are (1) the past history with systemic joint disease, such as autoimmune disease, (2) the patient with history of knee surgery or waiting for the total knee replacement, (3) any disease that affect the function of lower extremities, such as trauma, tumor or compensation of abnormal posture, (4) the condition that cannot participate this study, (5) the subjects non-compliance with the protocol.

The Assessments including primarily the WOMAC (VAS version, 3.1), VAS and the used dosage of Celebrex before and after treatment. The secondary assessments are (1) X ray, (2) Constitution in Chinese Medicine Questionnaire, (3) Short From-36, (4) erythrocyte sedimentation rate and C reactive protein, (5) Biomarkers: C-telopeptide of type II collagen, cartilage oligomeric matrix protein, Osteocalcin, Leptin, Interleukin-1, Interleukin-6, matrix metalloproteinase-3, matrix metalloproteinase-13, ADAMTS-4, transglutaminase-2, and (6) metabolomics.

详细描述

Introduction Knee osteoarthritis is a common disease of joint degeneration. Chronic inflammation is the major cause of this disease. One-third of the people over 65 years of age have Knee OA and the prevalence in women is more than in men. One-third of the people over 65 years of age have Knee OA and the prevalence in women is more than in men. The risk factors include age, weight, genetic factor, sex, bone density, and the past history of trauma or work. The more important risk factors are age and weight. These multiple factors make the change of knee joint, like chronic inflammation, joint remodeling and loss of function that make the change of joint homeostasis.

The diagnosis criteria of knee OA is based on two groups. In 1957, Kellgren and Lawrence established the criteria of radiological assessment and in 1986, Altman's group created the criteria of classification of idiopathic knee OA. In the beginning, only four pictures presented the four grade of knee OA without description. In 1963, Lawrence wrote the original description. Altman and his team used clinical signs combined with laboratory or radiography to established the diagnosis criteria. Now, the most used method is clinical and radiographic examination. In the clinical part, the patient should have knee pain with at least one of three items: age over than 50 years, the time of morning stiffness is less than 30 minutes or crepitus. In the radiography, the patient's X ray should show the definite osteophytes. The sensitivity can reach 91 percent and the specificity can reach 86 percent.

Knee joint is a diarthrodial joint. Two adjacent bones are covered by a layer of specialized articular cartilage and are encased in a connective tissue capsule lined by a synovial membrane, consisting of a thin cell layer of macrophages and fibroblasts. The main structural elements of knee include the articular cartilage (with chondrocytes), tidemark (separating the calcified and articular cartilage), calcified cartilage, and subchondral cortical and trabecular bone. The advanced osteoarthritic changes characterized by fissuring and fragmentation of the articular cartilage, chondrocyte proliferation and hypertrophy, duplication and advancement of the tidemark, expansion of the zone of calcified cartilage, thickening of the subchondral cortical plate and vascular invasion of the bone and calcified cartilage.

The signaling of cytokine is an important part of progression of knee OA. The initial is inflammation, maybe from cartilage or synovium. Then the hypertrophic chondrocyte and the macrophage of synovium will secret IL-1, 4, 13, TNF-α,β, MMP1,13 and ADAMTS 4, 5. The major function of MMP and ADAMTS is to degrade the articular cartilage.

The treatment of knee OA by OARSI (Osteoarthritis Research Society International) has one core treatment and four recommend treatment by different OA types. The core treatment includes strength training and exercise, weight management and education. The recommend treatment includes NSAIDs by oral or topical, acetaminophen, corticosteroid and duloxetine.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围
50 Years 至 75 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • age between 50~75 years old
  • diagnosis of osteoarthritis: The Clinical/Radiographic classification criteria of American College of Rheumatology, ACR
  • chronic knee pain over 3 months.

排除标准

  • the past history with systemic joint disease, such as autoimmune disease
  • the patient with history of knee surgery or waiting for the total knee replacement
  • any disease that affect the function of lower extremities, such as trauma, tumor or compensation of abnormal posture
  • the condition that cannot participate this study
  • the subjects non-compliance with the protocol

研究组 & 干预措施

TGF group (study group)

Experimental

Use TGF to treat osteoarthritis of the knee, 5g/time, 3 times a day, for 12 weeks.

干预措施: TGF (Drug)

TGFP group (placebo group)

Placebo Comparator

Use TGFP to treat osteoarthritis of the knee, 5g/time, 3 times a day, for 12 weeks.

干预措施: TGFP (Drug)

结局指标

主要结局

Visual Analogue Scale for pain

时间窗: Change from Baseline Visual Analogue Scale for pain at 4 months

To evaluate the status of knee pain when check point. Using 0-100 mm scale is to evaluate knee pain by visual analogue scale. "0" is no pain and "100" is the worst pain that subjects had experienced before. The subject gives the value under the moment of check point.

the used dosage of Celebrex

时间窗: Change from Baseline the used dosage of Celebrex at 4 months

To evaluate the dosage of Celebrex when check point

Western Ontario & McMaster Universities Osteoarthritis Index

时间窗: Change from Baseline WOMAC VAS version 3.1 at 4 months

This scale is the VAS version, 3.1 and divided into three sub-scales -- pain, stiffness and function. Pain (5 items): during walking, using stairs, in bed, sitting or lying, and standing. Stiffness (2 items): after first waking and later in the day. Physical Function (17 items): stair use, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy household duties, light household duties. Each item has 0-100 mm to evaluate the status and the higher values represent a worse outcome. These three sub-scales were summed to a total score (0-2400 mm).

次要结局

  • WHOQOL-BREF(Change from Baseline WHOQOL at 3 months)
  • CTX-II(Change from Baseline biomarkers at 4 months)
  • Osteocalcin(Change from Baseline biomarkers at 4 months)
  • MMP-13(Change from Baseline biomarkers at 4 months)
  • ADAMTS-4(Change from Baseline biomarkers at 4 months)
  • TG-2(Change from Baseline biomarkers at 4 months)
  • Mitochondria research--the expression of messenger ribonucleic acid in mtTFA(Change from Baseline the expression of mRNA in mtTFA at 4 months)
  • MMP-3(Change from Baseline biomarkers at 4 months)
  • Mitochondria research--the expression of protein in Nuclear respiratory factor 1(Change from Baseline the expression of protein in NRF1 at 4 months)
  • Mitochondria research--anti-oxidant capacity(Change from Baseline anti-oxidant capacity at 4 months)
  • hsCRP(Change from Baseline CRP at 4 months)
  • X ray(Change from Baseline X ray at 4 months)
  • Constitution in Chinese Medicine Questionnaire, CCMQ(Change from Baseline CCMQ at 4 months)
  • WHOQOL(Change from Baseline WHOQOL at 4 months)
  • IL-1(Change from Baseline biomarkers at 4 months)
  • Leptin(Change from Baseline biomarkers at 4 months)
  • Metabolomics(Change from Baseline metabolomics at 4 months)
  • Mitochondria research--mtDNA copy number(Change from Baseline mtDNA copy number at 4 months)
  • Mitochondria research--the expression of protein in Peroxisome proliferator-activated receptor-γ coactivator-1α(Change from Baseline the expression of protein in PGC-1α at 4 months)
  • Mitochondria research--the expression of protein in mtTFA(Change from Baseline the expression of protein in mtTFA at 4 months)
  • ESR(Change from Baseline ESR at 4 months)
  • COMP(Change from Baseline biomarkers at 4 months)
  • IL-6(Change from Baseline biomarkers at 4 months)
  • Mitochondria research--the expression of messenger ribonucleic acid in Peroxisome proliferator-activated receptor-γ coactivator-1α(Change from Baseline the expression of mRNA in PGC-1α at 4 months)
  • Mitochondria research--the expression of messenger ribonucleic acid in Nuclear respiratory factor 1(Change from Baseline the expression of mRNA in NRF1 at 4 months)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Hen-Hong Chang

Professor

China Medical University Hospital

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