Clinical Study to Predict the Risk of Bone Fractures With the POROUS Ultrasound Device

NCT06567054 | Recruiting

• 3 other identifiers: R3C-FX-02CIV-24-04-046776190115994
• Study Type: interventional
• Target: 1,600
• Locations: 3 countries
• Sites: 6

Brief Summary

Osteoporosis is a widespread medical condition among older people. It causes the bones to weaken and become more likely to break. Osteoporosis and bone fracture risk are currently evaluated by looking at clinical risk factors and measuring bone mineral density (BMD). The lower the BMD is, the higher the risk of osteoporotic fractures in the future. However, most bone fractures occur in people who do not have very low BMD values. This means that osteoporosis and fracture risk are often not diagnosed. Many of these non-diagnosed patients would benefit from treatment to reduce the probability of bone fractures. An X-ray device called DXA is the main tool used to diagnose osteoporosis and fracture risk clinically. DXA measures two-dimensional BMD in the hip and spine. The POROUS ultrasound device measures various properties of the outer layer of the bone in the lower leg. It has several advantages over DXA: (1) its image resolution is higher and three-dimensional; (2) it can detect bone changes without radiation; (3) it can detect these bone changes early and how they change over time. For this clinical study, we will recruit men and women over 55 years old. Most will have clinical risk factors, such as background diseases, for developing osteoporosis. The study is anticipated to last 4 years. Our major research questions are:

• Can the POROUS ultrasound device predict fracture risk?
• How does its performance compare to DXA?
• What is the safety of the new device? The participants will:
• answer questions about their medical history.
• be measured for height and weight, and take a physical test.
• be examined for the presence of 'silent' fractures in the spine.
• be examined at the beginning and end of the study with the two devices, DXA and POROUS.
• be called by telephone every six months and asked if they suffer from new bone fractures, take any medication that might affect their bones, or if their health status has changed. The participants will be monitored for 3 years.

Conditions

Healthy; Osteopenia; Osteoporosis

Keywords

Osteoporosis; Osteopenia; Bone Tissue; Diagnostic Imaging; Ultrasound; Ultrasonography; Ultrasonic Diagnosis; DEXA Scan; DXA Scan; Dual X-Ray Absorptiometry; Bone Fractures; Osteoporotic Fractures; Hip Fractures; Spinal Fractures; Low Bone Mineral Density

Outcome Measures

Primary Outcomes (2)

• Clinical Endpoint, Part 1 - POROUS-Score based on prevalent fractures

  Prevalent fractures are the focus of the analysis in Part 1, i.e., fractures that occurred prior to the Baseline visit. This is reflected in establishing corrected standardized odds ratio (sOR) for the POROUS R3C ultrasound device-derived POROUS-Score. Statistically significant discriminative power of the sOR will be achieved if the lower limit of the 90% confidence interval of the sOR is greater than 1. The POROUS-Score will be evaluated to demonstrate the discriminative performance of the POROUS R3C ultrasound device for prevalent fractures. Outcome measure: POROUS-Score (units on scale)

  12 months

• Clinical Endpoint, Part 2 - POROUS-Score based on incident fractures

  Incident fractures are the focus of the analysis in Part 2, i.e., fractures that occur after the Baseline visit until the EoS. This is reflected in establishing corrected standardized relative risk (sRR) for the POROUS R3C ultrasound device-derived POROUS-Score. Statistically significant prediction power of the sRR will be achieved if the lower limit of the 90% confidence interval of the sRR is greater than 1. The POROUS-Score will be evaluated to demonstrate the predictive performance of the POROUS R3C ultrasound device for incident fractures. Fractures, which are associated with cortical bone and/or increasing age, will be considered for collecting information on both prevalent and incident fractures. Any incident fractures caused by high-energy external forces will be excluded (censored) from the analysis. Outcome measure: POROUS-Score (units on scale)

  24 or 36 months

Secondary Outcomes (5)

• Safety Endpoint

  36 or 48 months

• Performance Endpoint, Part 1 - DXA T-score

  Immediately after the intervention

• Performance Endpoint, Part 1 - discriminative performance based on prevalent fractures

  12 months

• Performance Endpoint, Part 2 - DXA T-score

  Immediately after the intervention

• Performance Endpoint, Part 2 - predictive performance based on incident fractures

  24 or 36 months

Other Outcomes (38)

• Exploratory Performance Endpoint 1, Part 1 - ultrasound cortical sound velocity in the radial direction

  12 months

• Exploratory Performance Endpoint 1, Part 1 - cortical thickness

  12 months

• Exploratory Performance Endpoint 1, Part 1 - ultrasound frequency-dependent attenuation coefficient

  12 months

Study Arms (1)

Fracture risk prediction in middle-aged and elderly men and women

EXPERIMENTAL

All participants are examined with the investigational device (POROUS R3C ultrasound device) and a comparator device (DXA).

Device: Measurements with the POROUS R3C ultrasound device at the midshaft tibia; Device: DXA measurement of the hip and lumbar spine; Device: DXA-based Vertebral Fracture Assessment (VFA); Device: Projectional radiography of thoracic spine (alternative to DXA-based VFA, if VFA is not available)

Interventions

Measurements with the POROUS R3C ultrasound device at the midshaft tibia DEVICE

The POROUS R3C ultrasound device measures the cortical bone of the midshaft tibia. Ultrasound gel is first applied onto the skin surface, covering the region of interest, followed by placing the ultrasound transducer with a medical ultrasound gel pad placed in front of it. At the marked position on the leg, four technical measurement readings are performed: 2x CortBS and 2x Multifocus, with repositioning the probe between individual measurements, the chronological order of which is not crucial. Scanning time for each measurement takes 1-2 minutes. Out of the four measurements, the two optimal measurements (one for CortBS and one for Multifocus) are selected by the device, based on pre-defined quality criteria.

Fracture risk prediction in middle-aged and elderly men and women

DXA measurement of the hip and lumbar spine DEVICE

The following DXA measurements are to be performed: * Spine L1-4 * Hip left * Hip right (alternatively, if a valid measurement of the left hip is not possible) Scanning takes approximately 15 minutes. A maximum number of one repeat measurement is planned (e.g., hip or spine). Note: The DXA scan of the hip is performed on the same side of the body as the POROUS R3C ultrasound scan.

Fracture risk prediction in middle-aged and elderly men and women

DXA-based Vertebral Fracture Assessment (VFA) DEVICE

DXA-based Vertebral Fracture Assessment (VFA) of thoracic and lumbar spine from T4 to L5.

Fracture risk prediction in middle-aged and elderly men and women

Projectional radiography of thoracic spine (alternative to DXA-based VFA, if VFA is not available) DEVICE

Projectional radiography of thoracic spine T4-T12 and lumbar spine L1-L5.

Fracture risk prediction in middle-aged and elderly men and women

Eligibility Criteria

• Age: 56 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male individuals aged 56 to and including 85 years.
• Written informed consent has been obtained.
• Assessment of risk factors for hip and vertebral fractures:
• To avoid over- and under-recruiting with regard to the required sample size of participants with ≥ 2-fold increased age-and sex-adjusted risk for hip and vertebral fractures and participants with \< 2-fold increased age- and sex-adjusted risk, clinical risk factors necessary for the calculation of the risk for hip and vertebral fractures (based on the risk calculation scheme outlined in the DVO osteoporosis guideline) are assessed at Screening.
• Vertebral fractures:
• Vertebral fracture(s) during the last year
• Vertebral fracture(s) \> 12 months ago
• Number of vertebral fractures
• Maximal severity of vertebral fractures, according to Genant
• Hip fractures and other fractures:
• Hip fracture during the last year
• Hip fracture \> 12 months ago
• Humerus fracture
• Pelvic fracture
• Wrist (radius distal) fracture

You may not qualify if:

• Presence of diseases that rule out valid measurements with the DXA and/or POROUS R3C devices (e.g., fractures or metal implants in the examined bones, paralysis of the lower extremities, severe bone abnormalities).
• Inability to undergo the investigations required by the Clinical Investigation Plan (CIP) or cognitive limitations that preclude understanding of the Participant Information Sheet and the Informed Consent Document.
• Previous medical procedures involving exposure to a cumulative dose of ionising radiation deemed by the Investigator to exceed usual limits within standard of care.
• Pregnancy and breastfeeding
• Enrolment in any other interventional clinical study (current or during the last three months)
• Individual is in custody by order of an authority or a court of law.
• Close affiliation with an investigational site, e.g. employed at investigational site, close relative of an investigator, dependent person (e.g. student of the investigational site).
• Further, individuals who are being or have been treated within the indicated period prior to the beginning of the study with any of the following antiresorptive therapies are excluded from the clinical investigation:
• Bisphosphonates (due to residual effects of bisphosphonates after discontinuation):
• Intravenous (IV) zoledronate within the last 3 years.
• Oral alendronate within the last year, if (continuous) treatment duration before was \> 1 year.
• Oral risedronate within the last year, if (continuous) treatment duration before was \> 1 year.
• Ibandronate (IV or oral) within the last year, if (continuous) treatment duration before was \> 1 year.
• Denosumab within the last 3 years
• Hormone replacement therapy (HRT) including combination therapy or oestrogen alone in postmenopausal women within the last 6 months.

Sponsors & Collaborators

• POROUS GmbH: lead
• European Commission: collaborator

Study Sites (6)

Division for Endocrinology and Metabolism, Department of Medicine 3, Medical University Vienna

Vienna, 1090, Austria

RECRUITING

Department of Rheumatology, Charité Universitätsmedizin Berlin, Charite Campus Mitte

Berlin, State of Berlin, 10117, Germany

RECRUITING

Centre of Muscle and Bone Research (ZMK), Charité Universitätsmedizin Berlin, Campus Benjamin Franklin

Berlin, State of Berlin, 12207, Germany

RECRUITING

Department for Orthopedy, Trauma and Reconstructive Surgery, Section of Geriatric Traumatology, University Hospital Halle (Saale)

Halle, 06120, Germany

RECRUITING

Department of Endocrinology, Reproductive Medicine and Osteology Clinic for Gynecology and Obstetrics, University Hospital of Giessen and Marburg

Marburg, 35043, Germany

RECRUITING

VieCuri Medisch Centrum, Department of Internal Medicine, Venlo

Venlo, 5912 BI, Netherlands

RECRUITING

Related Publications (1)

• Armbrecht G, Nguyen Minh H, Massmann J, Raum K. Pore-Size Distribution and Frequency-Dependent Attenuation in Human Cortical Tibia Bone Discriminate Fragility Fractures in Postmenopausal Women With Low Bone Mineral Density. JBMR Plus. 2021 Sep 2;5(11):e10536. doi: 10.1002/jbm4.10536. eCollection 2021 Nov.

  PMID: 34761144 BACKGROUND

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis; Fractures, Bone; Osteoporotic Fractures; Hip Fractures; Spinal Fractures

Interventions

Weights and Measures

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Wounds and Injuries; Femoral Fractures; Hip Injuries; Leg Injuries; Spinal Injuries; Back Injuries

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Gabriele G Armbrecht, MD, PhD

  Zentrum für Muskel- und Knochenforschung

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irina Lorenz-Meyer

CONTACT

+49 176 34448596; lorenz-meyer@porous.care

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Comparative, single-cohort, interventional study model: investigational device vs. comparator device. Measurements are performed on the same cohort of participants: Part 1 - cross-sectional study; Part 2 - prospective study.

Study Record Dates

• First Submitted: June 28, 2024
• First Posted: August 22, 2024
• Study Start: March 3, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: June 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); NL (1); AU (1)