A Prospective, Single-cohort, Multicentre Clinical Investigation to Evaluate the Performance of POROUS R3C Ultrasound Device for Fracture Risk Prediction in Middle-aged and Elderly Men and Women
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,600
- 试验地点
- 12
- 主要终点
- Clinical Endpoint, Part 1 - POROUS-Score based on prevalent fractures
研究概览
简要总结
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.
详细描述
Background and purpose:
Currently, osteoporosis and fracture risk are indirectly evaluated via the assessment of risk factors and bone mineral density (BMD) measurement. Although BMD is currently the most important indicator for osteoporosis-associated bone fractures, most of those fractures occur in persons who do not show pathologically reduced BMD value. Therefore, osteoporosis is one of the most frequently underdiagnosed common diseases. Established guidelines for the diagnosis of osteoporosis recommend the assessment of fracture risk factors and the T-Score, which is derived from the measurement of areal bone mineral density (aBMD) by means of DXA at major fracture sites, i.e., spine and proximal femur. DXA is regarded as the "gold standard" well-established methodology to determine aBMD for diagnostic purposes. Epidemiological data emphasize the urgency of developing diagnostic tools that can improve fracture risk prediction so that patients can be treated with the appropriate anti-osteoporotic therapies. Current guidelines for diagnosis and treatment lead to treatment gaps. It is estimated that at least 80% of males and 77% of females who would benefit from osteoporosis treatment are neither diagnosed nor treated in Germany.
Device description:
The POROUS R3C ultrasound device enables a non-invasive, non-ionizing quantitative detection of microstructural bone changes. As opposed to diagnosis based on a combination of clinical risk factors and a relative decrease of BMD, the novel device enables detecting pathological changes of bone microstructure at an earlier timepoint as well as monitoring such changes in a longitudinal manner. In the course of this clinical investigation, data will be collected to establish relevant ultrasound-based physical biomarkers for the prediction of fracture risk.
Study design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 56 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
- •General risk factors:
- •Mother or father with hip fracture, if the participant is under 75 years of age
- •Significant alcohol consumption (50 g/day or more)
- •Smoking (currently > 10 cigarettes/day)
- •Chronic-obstructive pulmonary disease (COPD)
- •Body Mass Index (BMI) ≤ 20
- •Medication:
- •Proton pump inhibitors > 3 months
- •Oral glucocorticoids > 3 months (prednisone equivalent in mg/d)
- •Fall-associated risk factors/geriatrics:
- •Number of falls within the last year
- •Chronic hyponatremia
- •Depression/antidepressants
- •Anticonvulsants in epilepsy
- •Immobility (being dependent on a walking aid)
- •Alzheimer's disease/dementia
- •Parkinson's disease
- •Multiple sclerosis
- •Time up and Go Test > 12 seconds in participants ≥ 70 years of age
- •Endocrinology:
- •Diabetes mellitus Type I
- •Diabetes mellitus Type II (including time since onset)
- •Primary hyperparathyroidism
- •Thyroid-stimulating hormone (TSH) suppression (if yes, including TSH level)
- •Other diseases/medications:
- •Chronic heart failure
- •Monoclonal gammopathy of unclear significance (MGUS)
- •Chronic kidney disease (CKD) stages 3a, 3b, 4
- •Rheumatology:
- •Rheumatoid arthritis
- •Axial spondyloarthritis
排除标准
- •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.
- •Raloxifene within the last 6 months.
- •Individuals who are being or have ever been treated with any of the following anabolic therapies are excluded from the clinical investigation:
- •Teriparatide
- •Romosozumab
- •Abaloparatide.
研究组 & 干预措施
Fracture risk prediction in middle-aged and elderly men and women
All participants are examined with the investigational device (POROUS R3C ultrasound device) and a comparator device (DXA).
干预措施: Measurements with the POROUS R3C ultrasound device at the midshaft tibia (Device)
Fracture risk prediction in middle-aged and elderly men and women
All participants are examined with the investigational device (POROUS R3C ultrasound device) and a comparator device (DXA).
干预措施: DXA measurement of the hip and lumbar spine (Device)
Fracture risk prediction in middle-aged and elderly men and women
All participants are examined with the investigational device (POROUS R3C ultrasound device) and a comparator device (DXA).
干预措施: DXA-based Vertebral Fracture Assessment (VFA) (Device)
Fracture risk prediction in middle-aged and elderly men and women
All participants are examined with the investigational device (POROUS R3C ultrasound device) and a comparator device (DXA).
干预措施: Projectional radiography of thoracic spine (alternative to DXA-based VFA, if VFA is not available) (Device)
结局指标
主要结局
Clinical Endpoint, Part 1 - POROUS-Score based on prevalent fractures
时间窗: 12 months
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)
Clinical Endpoint, Part 2 - POROUS-Score based on incident fractures
时间窗: 24 or 36 months
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)
次要结局
- Safety Endpoint(36 or 48 months)
- 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 1 - DXA T-score(Immediately after the intervention)
- Performance Endpoint, Part 2 - predictive performance based on incident fractures(24 or 36 months)