Complex Molecular Etiology and Cellular Landscape of Hip Osteoarthritis

Recruiting

• Conditions: Osteoarthritis, Hip; Rheumatoid Arthritis
• Interventions: Procedure: Total hip arthroplasty

• Registration Number: NCT05278520
• Lead Sponsor: University of Turku

Brief Summary

The purpose of this study is to cast light on the highly complex etiology and cellular landscape of hip osteoarthritis by utilising single-cell and spatial omics.

Detailed Description

The specific objectives of this project are:

1. Using the latest single-cell RNA sequencing (scRNAseq) techniques the investigators aim to A) characterize what kind of cell populations are found in different synovial tissues and blood derived samples of OA patients, B) determine how the cell composition differs between arthritic and corresponding non-arthritic tissues, C) map the transcriptional and regulatory landscape of the cells mentioned in A and B focusing on the inflammatory responses, D) determine what are the key molecular pathways activated in OA.

2. To determine if some of the blood-derived immune cell populations or their products could be used as biomarkers for OA.

3. To map the whole transcriptome and proteome of OA and non-arthritic control tissue while keeping the morphological context with spatial omics technologies.

4. Further differentiation and identification of OA endotypes utilizing the single-cell and spatial omics data.

The project includes a Rheumatoid sub-study where the main objective is to compare arthritic tissue and peripheral blood constituents between OA and rheumatoid arthritis patients to explore the differences in the disease mechanisms.

Study Timeline

• Study First Submitted: 2022-03-03
• Study First Submitted QC: 2022-03-03
• Study First Posted: 2022-03-14
• Study Start: 2023-01-11
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-30
• Last Update Posted: 2024-12-04
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

Not provided

Exclusion Criteria

• The body mass index must be below 35
• Age < 18 or > 74
• The OA patients may not have diabetes, rheumatoid arthritis (RA), or metabolic syndrome.

For the Rheumatoid sub-study, the exclusion criteria are the same as above except for the RA.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Non-arthritic controls	Total hip arthroplasty	Fifteen adult patients who go through trauma-based emergency total hip arthroplasty and do not have arthritis.
RA cases	Total hip arthroplasty	Twenty-five adult patients who have rheumatoid arthritis in the hip joint.
OA cases	Total hip arthroplasty	Twenty-five adult patients who have hip osteoarthritis.

Primary Outcome Measures

Name	Time	Method
Characterization of cell populations in OA	Starting during the first quarter of 2025, ending by the last quarter of 2026.	Characterization of cell populations found in different synovial tissues and blood derived samples of OA patients utilising single-cell RNA sequencing solutions.
Comparison of cell populations between OA cases and controls	Starting during the first quarter of 2025, ending by the last quarter of 2026.	The investigators will determine how the cell composition differs between arthritic and corresponding non-arthritic tissues utilising single-cell RNA sequencing solutions.
Cellular landscape in OA	Starting during the last quarter of 2024, ending by the last quarter of 2026.	The investigators will map the transcriptional, regulatory and protein landscape of OA at single-cell and tissue (spatial) level.
Key molecular pathways of OA	Starting during the last quarter of 2025, ending by the last quarter of 2027.	The investigators will determine what are the key molecular pathways activated in OA.
Comparison of disease mechanisms between RA and OA	Starting during the last quarter of 2024, ending by the last quarter of 2028.	In the Rheumatoid sub-study the investigators will explore the differences in the disease mechanisms between OA and RA by comparing synovial tissues and peripheral blood sample constituents.

Secondary Outcome Measures

Name	Time	Method
Biomarkers for OA	Starting during the second half of 2026, ending by the last quarter of 2028.	The investigators will investigate if some of the blood-derived immune cell populations or their products could be used as biomarkers for OA.
OA endotypes	Starting during the first half of 2025, ending by the second half of 2027.	The investigators aim to identify and further differentiate OA endotypes by utilizing the single-cell and spatial data.

Trial Locations

Locations (4)

Helsinki University Hospital; 🇫🇮 Espoo, Uusimaa, Finland

PET-centre, University of Turku; 🇫🇮 Turku, Varsinais-Suomi, Finland

Turku Bioscience, University of Turku; 🇫🇮 Turku, Varsinais-Suomi, Finland

Turku University Hospital; 🇫🇮 Turku, Varsinais-Suomi, Finland