Musculoskeletal

Musculoskeletal clinical trials

Clario’s Musculoskeletal (MSK) ultrasound, radiology, and other imaging scientists and technologists and dedicated MSK project teams provide you with unmatched quality and independent image review in support of early and late phase clinical trials. Our expertise in MSK ultrasound, radiology, trial management and imaging includes support for the latest developments in imaging and endpoints and a deep background in rheumatoid and psoriatic arthritis, spondyloarthritis, osteoarthritis, osteoporosis, and other conditions.

Leverage customized project excellence

A thorough understanding of imaging endpoints enables us to assign the appropriate resources and scientific experts to match the needs of your study, from protocol design to regulatory submission. Furthermore, Clario’s leading central independent image acquisition and analysis process improves image quality and standardization, providing for highly reproducible results and inspection-ready data.

• Comprehensive site imaging technologist training
• MSK dedicated project teams
• Multi-center standardization and calibration of imaging equipment
• Full 21 CFR Part 11 and ICH/GCP compliance
• Global operations for local, 24/7 support
• Customized, real-time online reporting
• Network of Key Opinion Leaders

Overview

Advanced imaging capabilities

Radiography (X-ray)

Clario is well-versed with the most common imaging modality used in MSK clinical trial management for clinical indications such as rheumatoid arthritis, osteoarthritis, osteoporosis and other indications. Our team understands that the proper acquisition technique for the most precise assessments or measurements and has developed techniques to effectively and rapidly train imaging technologists around the globe. Whether performing a semiquantitative assessment of erosions and joint space narrowing in rheumatoid arthritis (RA) or vertebral fracture in osteoporosis, Clario’s experienced team and industry-leading processes ensure subtle changes are precisely measured.

Dual Energy X-Ray Absorptiometry (DXA)

DXA is the most widely available method for the non-invasive, quantitative assessment of bone mineral density (BMD). Ease of access, low radiation dose and patient compliance make DXA a favored tool for evaluation of both therapeutic response in osteoporosis, as well as the harmful effects of drugs that interfere with the normal bone metabolism or maturation. To ensure the quality of DXA BMD measurements, Clario’s experts offer services not only to standardize scan acquisition and analysis but also to monitor scanner calibration over time and among investigator sites. Our long relationship with the scientists at GE Lunar and Hologic has instilled deep knowledge of DXA in our team and ensures your trials run smoothly.

When BMD is not enough for your study needs, Clario also supports advanced analysis of DXA scans for assessing bone geometry by Hip Structural Analysis and bone texture using the Trabecular Bone Score (TBS). These analysis methods can be applied to most modern DXA scans and offer additional information about bone strength beyond BMD, which can help demonstrate the benefits of experimental treatments.

DXA is not limited to skeletal assessment and is widely used to measure body composition. The whole body DXA scan (available on many DXA scanners) also provides measurements of lean and fat mass in the total body as well as body subregions (e.g., arms, legs and trunk). Estimates of visceral adipose tissue mass are also available from whole-body DXA scans. Clario’s scientists can advise on the use of DXA for measuring fat in studies of obesity, diabetes, lipodystrophy and others as well as lean (muscle) mass in sarcopenia or wasting disease.

Magnetic Resonance Imaging (MRI)

MRI is a versatile imaging tool for assessing bones, joints, and muscles. Clario has completed numerous studies utilizing MRI and the MRI scoring systems recommended by OMERACT for both RA and PsA, partnering with the academic leaders responsible for the development of these systems to provide expert assessment of inflammation and joint destruction. Similarly, MR images of the sacroiliac joint and spine in patients with Spondyloarthrits (SpA) and Ankylosing Spondylitis (AS) can be evaluated for bone marrow edema and structural change with methods developed by Spondyloarthritis Research Consortium of Canada (SPARCC) and others.

Clario collaborates with world experts for the semiquantitative and quantitative assessment of MRI in knee osteoarthritis (OA). Whole Organ scoring methods like (WORMS) and MOAKS are proven techniques to assess disease severity and evaluate inflammatory and structural changes over time when performed by highly experienced MSK radiologists. Clario also supports the use of MRI for novel quantitative endpoints in knee OA using in-house analysis tools and through partnerships with specialty image analysis labs like Chondrometrics and Imorphics. Available endpoints include cartilage morphology and composition, articular bone shape, synovitis, and bone marrow edema. Successful use of these endpoints in multi-center clinical trials requires tightly controlled image acquisition to detect small changes associated with disease progression.

MR imaging of muscle employs sophisticated imaging techniques to quantify muscle volume (T1-weighted imaging), fat infiltration of muscle (multi-point Dixon imaging), and inflammation (T2 mapping). These techniques provide a comprehensive assessment of muscle features related to functional capacity and allow high sensitivity to detect change associated with therapeutic interventions, exercise regimens, and wasting conditions.

Quantitative Computed Tomography (QCT)

Understanding the effect of a drug on bone strength often requires methods more sophisticated than DXA. QCT uses clinical CT scanners, calibration tools and advanced software to measure volumetric BMD, bone geometry and even to make estimates of bone strength. Clario scientists have been pioneers in QCT research for decades and have supervised the majority of clinical trials using QCT to evaluate bone strength. Using carefully designed, low-dose acquisition protocols, Clario has trained scores of imaging facilities around the world to collect high-quality images for measuring QCT BMD of the spine, femur, forearm and knee. Proprietary calibration phantoms and custom-built software provide the means for detailed assessment of cortical, trabecular and integral BMD as well as bone geometry and strength indices. Partnering with O.N. Diagnostics, Clario provides estimates of bone strength using finite element analysis techniques validated by mechanical testing of bone specimens. These methods provide insights into the benefits of bone-building therapies. For example, in early phase trials, QCT allows a detailed comparison of responses in different treatment arms or even to approved therapies, allowing you to make critical program decisions with confidence. QCT techniques can also provide more power to detect or discount potential deleterious effects of new drugs to address regulatory questions about bone toxicity.

When bone quality or microarchitecture is critical to your research questions, Clario has the expertise and track record to employ high-resolution peripheral QCT for submillimeter resolution of cancellous bone. With HR-pQCT, bone microarchitecture like trabecular thickness and spacing, trabecular number, and cortical porosity can be interrogated in vivo, answering research questions about method-of-action not previously available in a multi-center setting.

Focus areas

Our experience with MSK trial radiology, ultrasound, and imaging includes support for the following indications and areas:

MSK disease and orthopedics

• Osteoporosis
• Osteoarthritis
• Fracture Healing & Repair
• Cartilage Repair
• Joint Arthroplasty
• Spine Arthroplasty
• Spine Arthrodesis

Rheumatic diseases

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Spondyloarthritis & Ankylosing Spondylitis
• Gout
• Sjogren’s Disease

Pediatric indications

• Juvenile Idiopathic Arthritis
• Growth Hormone Deficiency
• Osteogenesis Imperfecta
• Achondroplasia
• Fibrodysplasia Ossificans Progressiva
• Duchenne Muscular Dystrophy
• Obesity
• Diabetes
• HIV

Bone safety assessment

• Diabetes
• HIV
• Endometriosis
• Uterine Fibroids
• COPD
• Asthma
• Obesity

Also, Clario enables precise lung function testing to measure both the drug effect and progress of the disease using purpose-built devices and software customized to your protocol workflow for nearly 100% acceptable data in real-time. Click here to learn more about Clario Respiratory Solutions for MSK.