Clinical trial NCT05218122: Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited
Official title: To Explore the Characteristics of LKD Syndrome and PBS Syndrome of Knee Osteoarthritis Which Based on the Enhancement of Inflammatory Response Caused by the Inhibition of TGF-β/Smad Signal Pathway
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Knee Osteoarthritis
Syndrome
Traditional Chinese Medicine
Keywords: TGF-β/Smad signaling pathway
disease and syndrome cell model
knee osteoarthritis
syndrome
traditional Chinese medicine
Lead sponsor: Dongzhimen Hospital, Beijing
Sponsor class: OTHER
First posted: 2022-02-01
Enrollment: 340
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Among the outpatients and inpatients in Dongzhimen Hospital of Beijing University of traditional Chinese medicine from December 2021 to August 2024, 150 cases of liver and kidney deficiency syndrome and 300 cases of phlegm and blood stasis syndrome were taken respectively. All patients met the diagnosis of knee osteoarthritis and met the inclusion criteria. Another 40 cases of normal control group were taken.

Brief summary: 1. Through research and analysis, the levels of upstream and downstream factors related to TGF-β/Smad signaling pathway and inflammatory response factor related factors in serum, blood cells, articular fluid, urine, tongue covering and discarded tissues after surgery of patients with LKD syndrome and PBS syndrome of knee osteoarthritis were obtained, and the syndrome characteristics were further obtained.
2. Through research and analysis, the index levels of multiple omics detection in serum, blood cells, joint fluid, urine, tongue coating and discarded tissues of patients with LKD syndrome and PBS syndrome of knee osteoarthritis were obtained, and the syndrome characteristics were further obtained.
3. The severity of syndrome was quantified by syndrome score scale and the correlation between the above results and the syndrome score of patients with knee osteoarthritis with LKD syndrome and PBS syndrome was studied in combination with imaging characteristics.
4. To establish a "disease and syndrome cell model" and test relevant indicators to support the above research.
5. Through the analysis of the above research results, the possible mechanism is analyzed to provide an objective basis for the biological basis of the syndrome and relevant evidence for the clinical diagnosis and treatment of knee osteoarthritis with traditional Chinese medicine.

Detailed description: 1. Through research and analysis, the levels of upstream and downstream factors related to TGF-β/Smad signaling pathway and inflammatory response factor related factors in serum, blood cells, articular fluid, urine, tongue covering and discarded tissues after surgery of patients with liver and kidney deficiency syndrome and phlegm and blood stasis syndrome of knee osteoarthritis were obtained, and the syndrome characteristics were further obtained.
2. Through research and analysis, the index levels of multiple omics detection in serum, blood cells, joint fluid, urine, tongue coating and discarded tissues of patients with liver and kidney deficiency syndrome and phlegm and blood stasis syndrome of knee osteoarthritis were obtained, and the syndrome characteristics were further obtained.
3. The severity of syndrome was quantified by syndrome score scale and the correlation between the above results and the syndrome score of patients with knee osteoarthritis with liver and kidney deficiency syndrome and phlegm and blood stasis syndrome was studied in combination with imaging characteristics.
4. To establish a "disease and syndrome cell model" and test relevant indicators to support the above research.
5. Through the analysis of the above research results, the possible mechanism is analyzed to provide an objective basis for the biological basis of the syndrome and relevant evidence for the clinical diagnosis and treatment of knee osteoarthritis with traditional Chinese medicine.

Eligibility criteria: Inclusion Criteria:

1. Inclusion criteria of liver and kidney deficiency syndrome and phlegm and blood stasis syndrome in knee osteoarthritis

   * Age 20-80 years old, in line with the diagnostic criteria of Western medicine;
   * In accordance with the diagnostic criteria of TCM syndromes, it belongs to liver and kidney deficiency syndrome and phlegm and blood stasis syndrome;
   * Patients who are willing to participate in the survey and have good compliance;
   * Voluntary signing of informed consent;
2. Inclusion criteria of normal control group

   * Age 20-80 years old.
   * Patients who are willing to participate in the survey and have good compliance.
   * It does not meet the diagnostic criteria of knee osteoarthritis.
   * Voluntarily sign informed consent.

Exclusion Criteria:

* Complications affecting joints, such as psoriasis, syphilitic neuropathy, brown yellow disease, metabolic bone disease, etc;
* There were rheumatoid arthritis and ankylosing spondylitis;
* Late disabled and incapacitated;
* Pregnant or lactating women;
* Mentally ill.
* As long as one of the above 5 articles is met, it shall be excluded.

Primary outcomes:
measure: the differences of metabonomics
timeFrame: 3 years
measure: the differences of metabonomics in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: the differences of proteomics in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: the differences of proteomics
timeFrame: 3 years
measure: the differences of transcriptomics
timeFrame: 3 years
measure: the differences of transcriptomics in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: the related indexes of TGF- β/ Smad signaling pathway and inflammatory response
timeFrame: 3 years
measure: The clinical TCM scores of LKD
timeFrame: 3 years
measure: The clinical TCM scores of PBS
timeFrame: 3 years
measure: The grading scores of Kellgren Lawrence (K-L)
timeFrame: 3 years
measure: The grading scores of Yulish
timeFrame: 3 years
measure: Clinical data
timeFrame: 3 years
measure: Concentration of BLC (CXCL13)
timeFrame: 3 years
measure: Concentration of BLC (CXCL13) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of Eotaxin-1 (CCL11)
timeFrame: 3 years
measure: Concentration of Eotaxin-1 (CCL11) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of Eotaxin-2 (MPIF-2/CCL24)
timeFrame: 3 years
measure: Concentration of Eotaxin-2 (MPIF-2/CCL24) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of GCSF
timeFrame: 3 years
measure: Concentration of GCSF in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of GM-CSF
timeFrame: 3 years
measure: Concentration of GM-CSF in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of I-309 (TCA-3/CCL1)
timeFrame: 3 years
measure: Concentration of I-309 (TCA-3/CCL1) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of ICAM-1(CD54)
timeFrame: 3 years
measure: Concentration of ICAM-1(CD54) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IFN-gamma
timeFrame: 3 years
measure: Concentration of IFN-gamma in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-1 alpha (IL-1 F1)
timeFrame: 3 years
measure: Concentration of IL-1 alpha (IL-1 F1) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-1 beta (IL-1 F2)
timeFrame: 3 years
measure: Concentration of IL-1 beta (IL-1 F2) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-1 ra (IL-1 F3)
timeFrame: 3 years
measure: Concentration of IL-1 ra (IL-1 F3) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-2
timeFrame: 3 years
measure: Concentration of IL-2 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-4
timeFrame: 3 years
measure: Concentration of IL-4 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-5
timeFrame: 3 years
measure: Concentration of IL-5 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-6
timeFrame: 3 years
measure: Concentration of IL-6 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-6R
timeFrame: 3 years
measure: Concentration of IL-6R in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-7
timeFrame: 3 years
measure: Concentration of IL-7 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-8(CXCL8)
timeFrame: 3 years
measure: Concentration of IL-8(CXCL8) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-10
timeFrame: 3 years
measure: Concentration of IL-10 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-11
timeFrame: 3 years
measure: Concentration of IL-11 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-12 p40
timeFrame: 3 years
measure: Concentration of IL-12 p40 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-12 p70
timeFrame: 3 years
measure: Concentration of IL-12 p70 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-13
timeFrame: 3 years
measure: Concentration of IL-13 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-15
timeFrame: 3 years
measure: Concentration of IL-15 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-16
timeFrame: 3 years
measure: Concentration of IL-16 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of IL-17A
timeFrame: 3 years
measure: Concentration of IL-17A in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of MCP-1 (CCL2)
timeFrame: 3 years
measure: Concentration of MCP-1 (CCL2) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of M-CSF
timeFrame: 3 years
measure: Concentration of M-CSF in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of MIG (CXCL9)
timeFrame: 3 years
measure: Concentration of MIG (CXCL9) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of MIP-1
timeFrame: 3 years
measure: Concentration of MIP-1 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of alpha (CCL3) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of alpha (CCL3)
timeFrame: 3 years
measure: Concentration of MIP-1 beta (CCL4)
timeFrame: 3 years
measure: Concentration of MIP-1 beta (CCL4) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of MIP-1 delta (CCL15)
timeFrame: 3 years
measure: Concentration of MIP-1 delta (CCL15) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of PDGF-BB
timeFrame: 3 years
measure: Concentration of PDGF-BB in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of RANTES (CCL5)
timeFrame: 3 years
measure: Concentration of RANTES (CCL5) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of TIMP-1
timeFrame: 3 years
measure: Concentration of TIMP-1 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of TIMP-2
timeFrame: 3 years
measure: Concentration of TIMP-2 in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of TNF alpha
timeFrame: 3 years
measure: Concentration of TNF alpha in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of TNF beta (TNFSF1B)
timeFrame: 3 years
measure: Concentration of TNF beta (TNFSF1B) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of TNF RI (TNFRSF1A)
timeFrame: 3 years
measure: Concentration of TNF RI (TNFRSF1A) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of TNF RII(TNFRSF1B)
timeFrame: 3 years
measure: Concentration of TNF RII(TNFRSF1B) in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of Signaling pathway indicator
timeFrame: 3 years
measure: Concentration of Signaling pathway indicator in the cell models of disease-TCM syndrome
timeFrame: 3 years
measure: Concentration of Routine Blood Examination （Concentration of WBC, LYMPH%, MONO, NEUT%, LYMPH, MONO%, NEUT, BASO%, BASO, MCH, MCHC,ROW-CV, MPV, PLT, PDW, EO%, P-LCR, RBC, Hb, HCT）
timeFrame: 3 years
measure: Concentration of Blood Biochemistry (Concentration of TC, TG, HDL-C, LDL-C, Urea, Cr, UA, GLu, ALT, AST, TP, ALB, ALP, GGT, TBIL, DBIL, Mg, K, Na, Cl, Ca, P, Fe, CO2)
timeFrame: 3 years
measure: Concentration of Routine Urine Examination (Concentration of LEU, NIT, PRO, GLU-U, KET, URO, BIL, PH-U, SG, BLU)
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Dongzhimen Hospital
state: Beijing
Study officials:
References: