OSTEOMICS: Identifying Regulators of Bone Homeostasis (OSTEOMICS)

February 20, 2024 updated by: Relation Therapeutics

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

2000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • London, United Kingdom
        • Not yet recruiting
        • King's College Hospital
        • Contact:
        • Principal Investigator:
          • Ines Reichert
      • London, United Kingdom
        • Recruiting
        • Barts Health NHS Trust
        • Contact:
        • Principal Investigator:
          • Jonathan Ward
      • London, United Kingdom
        • Recruiting
        • West Middlesex University Hospital
        • Contact:
        • Principal Investigator:
          • Victor Babu
      • London, United Kingdom
      • London, United Kingdom
      • London, United Kingdom
        • Active, not recruiting
        • Luton & Dunstable University Hospital
      • London, United Kingdom
        • Not yet recruiting
        • Royal National Orthopaedic Hospital NHS Trust
        • Contact:
          • Richard Keen
        • Principal Investigator:
          • Richard Keen
    • Greater London
      • London, Greater London, United Kingdom, W1G 8HU
        • Active, not recruiting
        • Harley Street Specialist Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 110 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Participants undergoing range of orthopaedic surgeries.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Participant undergoing orthopaedic surgery
  • Patients with osteoarthritis undergoing total joint arthroplasty, osteotomy or arthrodesis of any joint (including hip, knee, shoulder, elbow, ankle).
  • Patients with fractured neck of femurs undergoing hemiarthroplasty or total hip arthroplasty, or other internal fixation procedure.
  • Patients undergoing acute low-velocity or fragility fracture fixation surgery.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acquisition of bone waste
Time Frame: Within 4 hours of resection.
Discarded bone waste to be used for the study of RNA.
Within 4 hours of resection.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acquisition of 10ml of blood.
Time Frame: Within 4 hours of resection.
Discarded blood to be used for genetic sequencing, and/or other downstream omics/assays
Within 4 hours of resection.
Completion of participant questionnaire
Time Frame: EDC entry within 1 week of surgery.
Patient metadata to be used to understand cohort and identify confounding factors.
EDC entry within 1 week of surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Relation Therapeutics

Collaborators

Barts & The London NHS Trust
Royal Free Hospital NHS Foundation Trust
Chelsea and Westminster NHS Foundation Trust
Royal National Orthopaedic Hospital NHS Trust
Bedfordshire Hospitals NHS Foundation Trust
Harley Street Specialist Hospital
Fitzrovia Hospital

Investigators

  • Principal Investigator: Raghbir Khakha, Harley Street Specialist Hospital & Fitzrovia Hospital/QASMC
  • Principal Investigator: Akash Patel, Royal Free London NHS Foundation Trust
  • Principal Investigator: Yegappan Kalairajah, Luton & Dunstable University Hospital, Bedfordshire Hospitals NHS Foundation Trust
  • Principal Investigator: Victor Babu, Chelsea and Westminster NHS Foundation Trust
  • Principal Investigator: Jonathan Ward, Barts & The London NHS Trust
  • Principal Investigator: Richard Keen, Royal National Orthopaedic Hospital NHS Trust
  • Principal Investigator: Ines Reichert, King's College Hospital NHS Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 12, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2032

Study Registration Dates

First Submitted

January 30, 2023

First Submitted That Met QC Criteria

February 8, 2023

First Posted (Actual)

February 17, 2023

Study Record Updates

Last Update Posted (Actual)

February 23, 2024

Last Update Submitted That Met QC Criteria

February 20, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RRx-Profiling-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

It is intended that the results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals.

When the data is no longer required by Relation Therapeutics, we may grant access to raw data (without linked identifiable patient data) and the right to publish freely. There will be no reference in the study results / reports / publications to any information that would identify participants. The final dataset, which may include a small number of select fields from the EDC database, will not contain any identifiable personal data.

IPD Sharing Time Frame

Data will not be released until the study is complete. Raw data files in the original format (e.g. fastq) and the accompanying anonymised phenotypic data will be uploaded to a public repository e.g. the NCBI database of Genotypes and Phenotypes (dbGaP) at https://www.ncbi.nlm.nih.gov/gap/.

IPD Sharing Access Criteria

Any database selected to host genetic data must require legally-binding data access agreements with participating researchers.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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