Advanced MR Imaging of Osteoarthritis (AMROA)

The utility of conventional imaging in the development of new treatments for osteoarthritis (OA) is hindered by:

1. Difficulty in non-invasively evaluating the initial response to potential new treatment options. OA typically develops over a long time period, so evaluating the efficacy of new treatment options over a timeframe relevant to experimental medicine studies is difficult.
2. Inadequate methods of disease quantification and stratification. OA is a heterogeneous condition and identifying which subgroups of patients are most likely to benefit from new treatments is crucial.

Novel magnetic resonance (MR) imaging acquisition and analysis techniques have the potential to solve these problems. However, their reliability needs to be fully established and knowledge of likely effect sizes is required to inform sample size considerations for further longitudinal/interventional studies.

This study aims to help address these issues by:

1. Calculating effect sizes for MR measurements to inform sample size calculations for future studies.
2. Assessing the reliability of a multiparametric MR protocol for assessment of the knee joint.

The investigators will examine a single knee of an initial 15 participants with MR. Participants will be drawn from two groups: (1) 10 participants aged 40-60 years old with clinical and x-ray features of OA and (2) 5 control subjects (matched to cases for age, sex and body mass index in a 1:2 ratio) who do not have clinical features of OA.

Participants will undergo an initial (baseline) MR examination, followed by repeat MR examinations at approximately 1 month and 1 year following the baseline examination.

This will allow us to assess both the reliability of our MR measurements and the expected progression in our MR measurements in OA subjects in the absence of any disease-modifying intervention.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Addenbrooke's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Group 1 will consist of 10 patients aged 40-60 who have presented to the Orthopaedic clinic with a painful knee, and have mild/moderate OA on plain radiographs (Kellgren-Lawrence grade 2-3).

Group 2 will consist of 5 healthy volunteer controls, matched (1:2 ratio) to cases for age, sex and body mass index who do not have knee pain.

Description

Group 1 Inclusion Criteria:

• Meets American College of Rheumatology (ACR) criteria for OA
• Kellgren-Lawrence grade 2-3 OA on knee radiograph
• Medial compartment predominant disease
• Neutral alignment
• Aged 40-60
• Body Mass Index (BMI) < 35 kg per square meter
• Ambulatory and in good general health

Group 2 Inclusion Criteria:

• No current symptoms of knee pain or stiffness or other clinical features of OA
• Aged 40-60
• BMI < 35 kg per square meter
• Ambulatory and in good general health

Exclusion Criteria (both groups):

• History of ipsilateral lower limb fracture
• History of ipsilateral lower limb surgery (including arthroscopy)
• Metabolic bone disease
• Inflammatory arthritis
• Haematological malignancy
• Paget's disease
• Bone metastases
• Contraindication to MR imaging (e.g. pacemaker, severe claustrophobia)
• Contraindication to intravenous gadolinium based contrast medium administration (see 'Ethical Considerations' section)
• Unable to consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy volunteers
Osteoarthritis patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean cartilage T1rho relaxation time (milliseconds)		1 year
Mean cartilage T2 relaxation time (milliseconds)		1 year
Mean cartilage T1 relaxation time post gadolinium (milliseconds)	Derived from delayed gadolinium enhanced MR of cartilage (dGEMRIC)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Osteoarthritis Knee Score (MOAKS) (arbitrary units)	Semiquantitative scoring system	1 year
Cartilage thickness values (millimeters)	Surface-based comparison using statistical parametric mapping	1 year
Subchondral bone area (millimeters squared)		1 year
Dynamic contrast enhanced (DCE) quantitation of parameters	Multiple DCE parameters calculated allowing description of enhancement rate and pattern of synovium	1 year
Subchondral bone texture index (arbitrary units)		1 year
Osteochondral junction integrity (semiquantitative grading, arbitrary units)		1 year

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2017
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: August 22, 2016
• First Submitted That Met QC Criteria: August 25, 2016
• First Posted (Estimate): August 30, 2016

Study Record Updates

• Last Update Posted (Actual): January 15, 2019
• Last Update Submitted That Met QC Criteria: January 11, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: 609/M/C/1670