Complex Molecular Etiology and Cellular Landscape of Hip Osteoarthritis (OASEQ)

Studies on the Complex Molecular Etiology and Cellular Landscape of Hip Osteoarthritis

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 transcriptomics.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Osteoarthritis, Hip
• Intervention / Treatment: Procedure: Total hip arthroplasty

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, D) determine what are the key molecular pathways activated in OA.
2. To determine if some of the blood-derived immune cell populations could be used as biomarkers for OA.
3. To map the whole transcriptome of OA and non-arthritic control tissue while keeping the morphological context with spatial transcriptomics technologies.
4. Further differentiation and identification of OA endotypes utilizing the single-cell and spatial 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 Type: Observational
• Enrollment (Estimated): 65

Contacts and Locations

• Study Contact: Name: Lea Mikkola, PhD; Phone Number: +358404143300; Email: limikk@utu.fi

Study Locations

• Finland
  • Uusimaa
    • Espoo, Uusimaa, Finland
      • Recruiting
      • Helsinki University Hospital
      • Contact: Anna Vasara, MD, PhD; Email: anna.vasara@hus.fi
      • Principal Investigator: Anna Vasara, MD, PhD
  • Varsinais-Suomi
    • Turku, Varsinais-Suomi, Finland
      • Active, not recruiting
      • PET-centre, University of Turku
    • Turku, Varsinais-Suomi, Finland
      • Active, not recruiting
      • Turku Bioscience, University of Turku
    • Turku, Varsinais-Suomi, Finland
      • Recruiting
      • Turku University Hospital
      • Contact: Pjotr Sarantsin, MD; Email: Pjotr.Sarantsin@tyks.fi
      • Principal Investigator: Pjotr Sarantsin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients of the HUS (Joint Authority of the Helsinki and Uusimaa Hospital District) Center of Arthroplasty and the Orto Surgical Hospital of Turku University.

Description

Inclusion Criteria for the main (OA) study:

Cases: Adult patients with osteoarthritis in the hip joint and who are going through an elective total hip arthroplasty.

Controls: Non-arthritis adult patients who are going through a trauma-based emergency total hip arthroplasty.

----

Inclusion Criteria for the Rheumatoid sub-study:

Adult patients with rheumatoid arthritis in the hip joint and who are going through an elective total hip arthroplasty.

----

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
OA cases; Twenty-five adult patients who have hip osteoarthritis.	Procedure: Total hip arthroplasty; Hip joint replacement surgery. Elective for RA and OA cases.
RA cases; Twenty-five adult patients who have rheumatoid arthritis in the hip joint.	Procedure: Total hip arthroplasty; Hip joint replacement surgery. Elective for RA and OA cases.
Non-arthritic controls; Fifteen adult patients who go through trauma-based emergency total hip arthroplasty and do not have arthritis.	Procedure: Total hip arthroplasty; Hip joint replacement surgery. Elective for RA and OA cases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of cell populations in OA	Characterization of cell populations found in different synovial tissues and blood derived samples of OA patients utilising scRNAseq solutions.	Starting during the last quarter of 2022, ending by the last quarter of 2024.
Comparison of cell populations between OA cases and controls	The investigators will determine how the cell composition differs between arthritic and corresponding non-arthritic tissues utilising scRNAseq solutions.	Starting during the last quarter of 2022, ending by the last quarter of 2024.
Cellular landscape in OA	The investigators will map the transcriptional and regulatory landscape of OA at single-cell and tissue (spatial) level.	Starting during the second quarter of 2023, ending by the last quarter of 2024.
Key molecular pathways of OA	The investigators will determine what are the key molecular pathways activated in OA.	Starting during the second quarter of 2023, ending by the last quarter of 2024.
Comparison of disease mechanisms between RA and OA	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.	Starting during the last quarter of 2022, ending by the last quarter of 2024.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers for OA	The investigators will investigate if some of the blood-derived immune cell populations could be used as biomarkers for OA.	Starting during the second half of 2023, ending by the first half of 2025.
OA endotypes	The investigators aim to identify and further differentiate OA endotypes by utilizing the single-cell and spatial data.	Starting during the first half of 2024, ending by the second half of 2025.

Collaborators and Investigators

• Sponsor: University of Turku
• Collaborators: Turku University Hospital; Helsinki University Central Hospital
• Investigators: Principal Investigator: Lea Mikkola, PhD, Turku Bioscience, University of Turku

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 14, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Osteoarthritis; Rheumatoid arthritis; Single-cell RNA sequencing; Spatial transcriptomics
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Osteoarthritis; Osteoarthritis, Hip
• Other Study ID Numbers: 2022OASEQ

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No