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

NCT05218122 | Unknown

• 1 other identifier: 2021DZMEC-139-03
• Study Type: observational
• Target: 340
• Locations: 1 country
• Sites: 1

Brief Summary

1. 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. 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. 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. 4.To establish a "disease and syndrome cell model" and test relevant indicators to support the above research.
5. 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.

Conditions

Knee Osteoarthritis; Syndrome; Traditional Chinese Medicine

Keywords

TGF-β/Smad signaling pathway; disease and syndrome cell model; knee osteoarthritis; syndrome; traditional Chinese medicine

Outcome Measures

Primary Outcomes (99)

• 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

• 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

• 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

• 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

• 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

• 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

• the related indexes of TGF- β/ Smad signaling pathway and inflammatory response

  Histological and pathological examination is used to detect the related indexes of TGF- β/ Smad signaling pathway and inflammatory response.

  3 years

• 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

• 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

• 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

• The grading scores of Yulish

  The minimum value is 0 and maximum value is 4, and higher scores mean a worse outcome.

  3 years

• 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

• Concentration of BLC (CXCL13)

  Concentration of BLC (CXCL13) will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• 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

• 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

• 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

• Concentration of GCSF

  Concentration of GCSF will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of GM-CSF

  Concentration of GM-CSF will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• 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

• 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

• 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

• Concentration of IFN-gamma

  Concentration of IFN-gamma will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Concentration of IL-2

  Concentration of IL-2 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-4

  Concentration of IL-4 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-5

  Concentration of IL-5 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-6

  Concentration of IL-6 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-6R

  Concentration of IL-6R will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-7

  Concentration of IL-7 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• 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

• Concentration of IL-10

  Concentration of IL-10 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-11

  Concentration of IL-11 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• 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

• 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

• 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

• Concentration of IL-13

  Concentration of IL-13 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-15

  Concentration of IL-15 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-16

  Concentration of IL-16 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of IL-17A

  Concentration of IL-17A will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• 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

• Concentration of M-CSF

  Concentration of M-CSF will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of MIG (CXCL9)

  Concentration of MIG (CXCL9) will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of MIP-1

  Concentration of MIP-1 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• Concentration of alpha (CCL3)

  Concentration of alpha (CCL3) will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• 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

• 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

• Concentration of PDGF-BB

  Concentration of PDGF-BB will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of RANTES (CCL5)

  Concentration of RANTES (CCL5) will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of TIMP-1

  Concentration of TIMP-1 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of TIMP-2

  Concentration of TIMP-2 will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• Concentration of TNF alpha

  Concentration of TNF alpha will be detected by ELISA in LKD group, PBS group and NC group.

  3 years

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

LKD syndrome

liver and kidney deficiency syndrome

Other: cross-sectional study without intervention

PBS syndrome

phlegm and blood stasis syndrome

Other: cross-sectional study without intervention

NC group

Normal Control group

Other: cross-sectional study without intervention

Interventions

cross-sectional study without intervention OTHER

cross-sectional study without intervention

LKD syndrome; NC group; PBS syndrome

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dongzhimen Hospital, Beijing: lead

Study Sites (1)

Dongzhimen Hospital

Beijing, Beijing Municipality, 100700, China

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Syndrome; Disease

Interventions

Cross-Sectional Studies; Methods

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epidemiologic Studies; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: February 1, 2022
• Study Start: December 24, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 1, 2022

Record last verified: 2022-01

Locations

CN (1)