OSTEOMICS: Identifying Regulators of Bone Homeostasis

Osteoarthritis Clinical Trial

— OSTEOMICS  

Official title:

OSTEOMICS: Identifying Regulators of Bone Homeostasis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05732870
• Other study ID #: RRx-Profiling-001
• Status: Recruiting
• Start date: January 12, 2023
• Est. completion date: December 2032

Study information

• Verified date: February 2024
• Source: Relation Therapeutics
• Contact: Jake Taylor-King, DPhil
• Phone: 447387227904
• Email: jake[@]relationrx.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Diseases of bone associated with ageing, including osteoporosis (OP) and osteoarthritis (OA), reduce bone mass, bone strength and joint integrity. Current non-surgical approaches are limited to pharmaceutical agents that are not disease modifying and have poor patient tolerability due to side effect profiles. Developing a fundamental understanding of cellular bone homeostasis, including how key cell types affect tissue health, and offering novel therapeutic targets for prevention of bone disease is therefore essential. This is the focus of OSTEOMICS.

A number of factors have been linked to increased risk of bone disease, including genetic predisposition, diet, smoking, ageing, autoimmune disorders and endocrine disorders. In our study, we will recruit patients undergoing elective and non-elective orthopaedic surgery and obtain surgical bone waste for analysis. This will capture a cohort of patients with bone disorders like OP and OA, in addition to patients without overt clinical bone disease. We will study the relationship between the molecular biology of bone cells, bone structure, genetics (DNA) and environmental factors with the aim of identifying and validating novel therapeutic targets.

We will leverage modern single cell technologies to understand the diversity of cell types found in bone. These technologies have now led to the characterisation of virtually every tissue in the body, however bone and bone-adjacent tissues are massively underrepresented due to the anatomical location and underlying technical challenges. Early protocols to demineralise bone and perform single cell profiling have now been developed. We will systematically scale up these efforts to observe how genetic variation at the population level leads to alterations in bone structure and quality.

Over the next 10 years, we will generate data to comprehensively characterise bone across health and disease, use machine learning to drive analysis, and experimentally validate hypotheses - which will ultimately contribute to developing the next generation of therapeutic agents.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 2032
• Est. primary completion date: December 2027
• Gender: All
• Age group: 18 Years to 110 Years

Eligibility

Inclusion Criteria:

1. Patients with osteoarthritis undergoing total joint arthroplasty, osteotomy or arthrodesis of any joint (including hip, knee, shoulder, wrist, elbow, ankle).

2. Patient with fractured neck of femurs undergoing hemiarthroplasty or total hip arthroplasty, or other internal fixation procedure.

3. Patients undergoing acute low-velocity or fragility fracture fixation surgery.

4. Patients aged between 18-110 years old with capacity to consent.

Since deteriorating bone health including diseases like osteoporosis are primarily conditions of older age there is no practical upper age-limit. However, study involvement is limited by suitability for surgery which encompasses multiple factors considered on an individual case basis including age, frailty, comorbidities, baseline mobility, renal function and ability to consent (for instance due to dementia or delirium).

We note that our inclusion criteria is purposefully broad as we aim to deduce trends across a wide range of conditions and backgrounds.

Exclusion Criteria:

1. Patients unable to provide informed consent.

2. Patients with suspected/established underlying malignancy.

3. Patients with suspected/established osteomyelitis.

4. Patients with suspected/established bloodborne disease

5. Patients who are currently a subject of a clinical trial involving an investigational medicinal product.

Related Conditions & MeSH terms

• Bone Diseases
• Bone Fracture
• Bone Marrow Disease
• Bone Marrow Diseases
• Fractures, Bone
• Osteoarthritis
• Osteoporosis

Intervention

Procedure:
• Relevant orthopaedic surgery
Inclusion criteria is purposefully broad to examine a range of discarded bone waste. Therefore, a large number of surgical interventions are relevant.

Locations

Country	Name	City	State
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Chase Farm Hospital	London
United Kingdom	Fitzrovia Hospital/QASMC	London
United Kingdom	Harley Street Specialist Hospital	London	Greater London
United Kingdom	King's College Hospital	London
United Kingdom	Luton & Dunstable University Hospital	London
United Kingdom	Royal National Orthopaedic Hospital NHS Trust	London
United Kingdom	West Middlesex University Hospital	London

Sponsors (8)

Lead Sponsor	Collaborator
Relation Therapeutics	Barts & The London NHS Trust, Bedfordshire Hospitals NHS Foundation Trust, Chelsea and Westminster NHS Foundation Trust, Fitzrovia Hospital, Harley Street Specialist Hospital, Royal Free Hospital NHS Foundation Trust, Royal National Orthopaedic Hospital NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acquisition of bone waste	Discarded bone waste to be used for the study of RNA.	Within 4 hours of resection.
Secondary	Acquisition of 10ml of blood.	Discarded blood to be used for genetic sequencing, and/or other downstream omics/assays	Within 4 hours of resection.
Secondary	Completion of participant questionnaire	Patient metadata to be used to understand cohort and identify confounding factors.	EDC entry within 1 week of surgery.