Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited

Knee Osteoarthritis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05218122
• Other study ID #: 2021DZMEC-139-03
• Status: Recruiting
• Start date: December 24, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2022
• Source: Dongzhimen Hospital, Beijing
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee
• Syndrome
• Traditional Chinese Medicine

Intervention

Other:
• cross-sectional study without intervention
cross-sectional study without intervention

Locations

Country	Name	City	State
China	Dongzhimen Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Dongzhimen Hospital, Beijing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the differences of metabonomics	The differences of metabonomics in blood, urine and tongue coating will be detected by metabonomics in LKD group, PBS group and NC group.	3 years
Primary	the differences of metabonomics in the cell models of disease-TCM syndrome	The differences of metabonomics in the cell models of disease-TCM syndrome will be detected by metabonomics.	3 years
Primary	the differences of proteomics in the cell models of disease-TCM syndrome	The differences of proteomics in the cell models of disease-TCM syndrome will be detected by proteomics.	3 years
Primary	the differences of proteomics	The differences of proteomics in blood, urine and tongue coating will be detected by proteomics in LKD group, PBS group and NC group.	3 years
Primary	the differences of transcriptomics	The differences of transcriptomics in blood, urine and tongue coating will be detected by transcriptomics in LKD group, PBS group and NC group.	3 years
Primary	the differences of transcriptomics in the cell models of disease-TCM syndrome	The differences of transcriptomics in the cell models of disease-TCM syndrome will be detected by transcriptomics.	3 years
Primary	the related indexes of TGF- ß/ Smad signaling pathway and inflammatory response	Histological and pathological examination is used to detect the related indexes of TGF- ß/ Smad signaling pathway and inflammatory response.	3 years
Primary	The clinical TCM scores of LKD	The minimum value is 0 and maximum value is 38, and higher scores mean a worse outcome.	3 years
Primary	The clinical TCM scores of PBS	The minimum value is 0 and maximum value is 41, and higher scores mean a worse outcome.	3 years
Primary	The grading scores of Kellgren Lawrence (K-L)	The minimum value is 0 and maximum value is 4, and higher scores mean a worse outcome.	3 years
Primary	The grading scores of Yulish	The minimum value is 0 and maximum value is 4, and higher scores mean a worse outcome.	3 years
Primary	Clinical data	Collect clinical data and formulate a unified questionnaire, including the name, age, gender, outpatient / inpatient number, past history, current medical history, imaging images and other relevant data of patients with knee osteoarthritis.	3 years
Primary	Concentration of BLC (CXCL13)	Concentration of BLC (CXCL13) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of BLC (CXCL13) in the cell models of disease-TCM syndrome	Concentration of BLC (CXCL13) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of Eotaxin-1 (CCL11)	Concentration of Eotaxin-1 (CCL11) will be detected by ELISA will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of Eotaxin-1 (CCL11) in the cell models of disease-TCM syndrome	Concentration of Eotaxin-1 (CCL11) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of Eotaxin-2 (MPIF-2/CCL24)	Concentration of Eotaxin-2 (MPIF-2/CCL24) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of Eotaxin-2 (MPIF-2/CCL24) in the cell models of disease-TCM syndrome	Concentration of Eotaxin-2 (MPIF-2/CCL24) will be detected by ELISA in the cell models of disease-TCM.	3 years
Primary	Concentration of GCSF	Concentration of GCSF will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of GCSF in the cell models of disease-TCM syndrome	Concentration of GCSF will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of GM-CSF	Concentration of GM-CSF will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of GM-CSF in the cell models of disease-TCM syndrome	Concentration of GM-CSF will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of I-309 (TCA-3/CCL1)	Concentration of I-309 (TCA-3/CCL1) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of I-309 (TCA-3/CCL1) in the cell models of disease-TCM syndrome	Concentration of I-309 (TCA-3/CCL1) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of ICAM-1(CD54)	Concentration of ICAM-1(CD54) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of ICAM-1(CD54) in the cell models of disease-TCM syndrome	Concentration of ICAM-1(CD54) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IFN-gamma	Concentration of IFN-gamma will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IFN-gamma in the cell models of disease-TCM syndrome	Concentration of IFN-gamma will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-1 alpha (IL-1 F1)	Concentration of IL-1 alpha (IL-1 F1) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-1 alpha (IL-1 F1) in the cell models of disease-TCM syndrome	Concentration of IL-1 alpha (IL-1 F1) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-1 beta (IL-1 F2)	Concentration of IL-1 beta (IL-1 F2) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-1 beta (IL-1 F2) in the cell models of disease-TCM syndrome	Concentration of IL-1 beta (IL-1 F2) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-1 ra (IL-1 F3)	Concentration of IL-1 ra (IL-1 F3) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-1 ra (IL-1 F3) in the cell models of disease-TCM syndrome	Concentration of IL-1 ra (IL-1 F3) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-2	Concentration of IL-2 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-2 in the cell models of disease-TCM syndrome	Concentration of IL-2 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-4	Concentration of IL-4 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-4 in the cell models of disease-TCM syndrome	Concentration of IL-4 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-5	Concentration of IL-5 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-5 in the cell models of disease-TCM syndrome	Concentration of IL-5 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-6	Concentration of IL-6 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-6 in the cell models of disease-TCM syndrome	Concentration of IL-6 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-6R	Concentration of IL-6R will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-6R in the cell models of disease-TCM syndrome	Concentration of IL-6R will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-7	Concentration of IL-7 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-7 in the cell models of disease-TCM syndrome	Concentration of IL-7 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-8(CXCL8)	Concentration of IL-8(CXCL8) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-8(CXCL8) in the cell models of disease-TCM syndrome	Concentration of IL-8(CXCL8) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-10	Concentration of IL-10 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-10 in the cell models of disease-TCM syndrome	Concentration of IL-10 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-11	Concentration of IL-11 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-11 in the cell models of disease-TCM syndrome	Concentration of IL-11 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-12 p40	Concentration of IL-12 p40 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-12 p40 in the cell models of disease-TCM syndrome	Concentration of IL-12 p40 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-12 p70	Concentration of IL-12 p70 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-12 p70 in the cell models of disease-TCM syndrome	Concentration of IL-12 p70 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-13	Concentration of IL-13 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-13 in the cell models of disease-TCM syndrome	Concentration of IL-13 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-15	Concentration of IL-15 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-15 in the cell models of disease-TCM syndrome	Concentration of IL-15 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-16	Concentration of IL-16 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-16 in the cell models of disease-TCM syndrome	Concentration of IL-16 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of IL-17A	Concentration of IL-17A will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of IL-17A in the cell models of disease-TCM syndrome	Concentration of IL-17A will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of MCP-1 (CCL2)	Concentration of MCP-1 (CCL2) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of MCP-1 (CCL2) in the cell models of disease-TCM syndrome	Concentration of MCP-1 (CCL2) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of M-CSF	Concentration of M-CSF will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of M-CSF in the cell models of disease-TCM syndrome	Concentration of M-CSF will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of MIG (CXCL9)	Concentration of MIG (CXCL9) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of MIG (CXCL9) in the cell models of disease-TCM syndrome	Concentration of MIG (CXCL9) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of MIP-1	Concentration of MIP-1 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of MIP-1 in the cell models of disease-TCM syndrome	Concentration of MIP-1 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of alpha (CCL3) in the cell models of disease-TCM syndrome	Concentration of alpha (CCL3) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of alpha (CCL3)	Concentration of alpha (CCL3) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of MIP-1 beta (CCL4)	Concentration of MIP-1 beta (CCL4) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of MIP-1 beta (CCL4) in the cell models of disease-TCM syndrome	Concentration of MIP-1 beta (CCL4) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of MIP-1 delta (CCL15)	Concentration of MIP-1 delta (CCL15) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of MIP-1 delta (CCL15) in the cell models of disease-TCM syndrome	Concentration of MIP-1 delta (CCL15) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of PDGF-BB	Concentration of PDGF-BB will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of PDGF-BB in the cell models of disease-TCM syndrome	Concentration of PDGF-BB will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of RANTES (CCL5)	Concentration of RANTES (CCL5) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of RANTES (CCL5) in the cell models of disease-TCM syndrome	Concentration of RANTES (CCL5) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of TIMP-1	Concentration of TIMP-1 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of TIMP-1 in the cell models of disease-TCM syndrome	Concentration of TIMP-1 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of TIMP-2	Concentration of TIMP-2 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of TIMP-2 in the cell models of disease-TCM syndrome	Concentration of TIMP-2 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of TNF alpha	Concentration of TNF alpha will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of TNF alpha in the cell models of disease-TCM syndrome	Concentration of TNF alpha will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of TNF beta (TNFSF1B)	Concentration of TNF beta (TNFSF1B) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of TNF beta (TNFSF1B) in the cell models of disease-TCM syndrome	Concentration of TNF beta (TNFSF1B) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of TNF RI (TNFRSF1A)	Concentration of TNF RI (TNFRSF1A) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of TNF RI (TNFRSF1A) in the cell models of disease-TCM syndrome	Concentration of TNF RI (TNFRSF1A) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of TNF RII(TNFRSF1B)	Concentration of TNF RII(TNFRSF1B) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Primary	Concentration of TNF RII(TNFRSF1B) in the cell models of disease-TCM syndrome	Concentration of TNF RII(TNFRSF1B) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Primary	Concentration of Signaling pathway indicator	Concentration of Signaling pathway indicator will be detected by ELISA, metabonomics, proteomics, transcriptomics in LKD group, PBS group and NC group.	3 years
Primary	Concentration of Signaling pathway indicator in the cell models of disease-TCM syndrome	Concentration of Signaling pathway indicator will be detected by ELISA, metabonomics, proteomics, transcriptomics in the cell models of disease-TCM syndrome.	3 years
Primary	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)	LKD group, PBS group and NC group's Routine Blood Examination will be detect by automated hematology analyzer.	3 years
Primary	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)	LKD group, PBS group and NC group's Blood Biochemistry will be detect by automatic biochemical analyzer.	3 years
Primary	Concentration of Routine Urine Examination (Concentration of LEU, NIT, PRO, GLU-U, KET, URO, BIL, PH-U, SG, BLU)	LKD group, PBS group and NC group's Routine Urine Examination will be detect by Urine analyzer.	3 years