Creation, Management and Analysis of a National Database of Patients Affected by Diseases of Phosphate Metabolism
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 试验地点
- 28
- 主要终点
- Prevalence and incidence evaluation
研究概览
简要总结
The goal of this observational study is to create, manage and analyze a multicenter national database of patients affected by diseases of phosphate metabolism, aimed at collecting and studying anamnestic, diagnostic, genetic, clinical, and therapeutic data in a relatively wide number of patients with these rare inherited metabolic disorders in Italy.
The study will include 28 specialist clinical centers of endocrinology, pediatric endocrinology, and pediatrics, located throughout the Italian territory, and to which patients refer from all the 20 regions of Italy.
Data will be collected over time, both in retrospective and prospective manners, during the 10-year duration of the study, starting from the recruiting visit (basal visit) and then during each follow-up visits patients will undergo for the control of disease at the recruiting clinical centers.
Collected data will include both the most classic traits of each disease and the less common ones, with the final goal of refining and deepening medical knowledge in the field of these rare inherited metabolic disorders, and, thus, to be able to define optimal tailored diagnostic, clinical, and therapeutic management of patients, improving their quality of life.
The main aspects this observational study aims to assess and clarify are:
- Evaluation of prevalence and incidence of diseases of phosphate metabolism in Italy, globally and for single different disorders
- Clinical and biochemical characterization of different diseases of phosphate metabolism (according to single disorders and different genetic base), through both cross-sectional and longitudinal analyses of collected data
- Evaluation of skeletal health and bone fragility in patients with diseases of phosphate metabolism, globally and based on single phosphate metabolism disorder, gender, and age
- Self-evaluation of health-related quality of life in patients with a disease of phosphate metabolism
- Over time evaluation of responses to therapies in patients with diseases of phosphate metabolism.
The study will include a single cohort of female and male patients of any age, affected by a disease of phosphate metabolism. The study does not include either any control group/comparison group or healthy volunteers.
The study itself does not involve any medical intervention or drug administration. Therapies for which response outcomes will be collected in the database, are those commonly employed for the treatment of diseases of phosphate metabolism, regardless of patients' inclusion in this observational study.
详细描述
- Background and rationale
Phosphorus is one of the most abundant elements in the human body, where it is found, mainly in the form of phosphate salts, in quantities of about 500-700 grams, of which about 85% is concentrated in bone tissue, where it is an important constituent of hydroxyapatite crystals. In soft tissues, phosphate is mainly found in the intracellular compartment as an essential component of various organic compounds, including nucleic acids and phospholipids of the cell membrane.
The concentration of circulating extracellular phosphate is finely regulated by hormones such as parathyroid hormone (PTH), the active form of vitamin D (1,25-dihydroxyvitamin D or calcitriol), and fibroblast growth factor 23 (FGF23). The latter belongs to a family of proteins, specifically responsible for regulating phosphate metabolism, which are called phosphatonins in their complex, and include FGF23, Phosphate Regulating Endopeptidase X-Linked (PHEX), Polypeptide N-Acetylgalactosaminyltransferase 3 (GALNT3), Klotho. Under normal conditions, the coordinated action of phosphotropic hormones modulates intestinal absorption of this mineral, its renal reabsorption, and bone mineralization, maintaining the balance between absorption and excretion and ensuring a normal blood concentration of phosphate between 2.5 and 4.5 mg/dl (0.81-1.45 mmol/L) in the adult organism. Bone phosphate serves as a deposit, capable of buffering changes in plasma and intracellular levels of phosphate. Alterations in the mechanisms that regulate phosphate metabolism are responsible for the development of a group of rare disorders that are collectively defined as phosphate metabolism diseases, and include diseases caused by excess phosphate (hyperphosphatemic disorders), such as calcinosis, and diseases caused by deficiency of phosphate (hypophosphatemic disorders), such as hypophosphatemic rickets.
Phosphate metabolism diseases are classified as rare diseases. As reported by the "Osservatorio Malattie Rare (OMAR)", in the European Union a disease is defined as rare when its prevalence, understood as the number of cases present in a given population, is less than 0.05 percent of the population (no more than one case in every 2,000 people). The rarity of these diseases makes them difficult to study, and unfortunately, in many cases, scientific and medical knowledge of rare diseases is scarce and inadequate, and limited to few case reports. Due to the lack of sufficient medical and scientific knowledge, many patients affected by rare diseases remain undiagnosed and their diseases remain unrecognized. It is, therefore, essential that doctors and researchers working in the field of rare diseases increasingly work in networks to share the results of their research and to progress more effectively in the knowledge and clinical management of these diseases. In this perspective, implementing and detailing as much as possible the knowledge on the epidemiology, clinical and therapeutic history, primary and secondary manifestations of diseases of phosphate metabolism and the response to employed therapies, both in cross-sectional and longitudinal manners, with constant follow-up assessments of patients is essential not only to improve the clinical management of single patients, but also to allow better planning of social, political and health interventions for these pathologies and, overall, improve the quality of life of patients.
For this reason, it is extremely important to create a national multicenter database, such as the one proposed by this study, which is able to collect a relatively high number of patients affected by diseases of phosphate metabolism, whose cases are carefully studied in every aspect, both retrospectively and prospectively, following the course of the disease over time. Such a database has never been prepared in Italy before, and the availability of clinical data relating to diseases of phosphate metabolism has been limited to individual clinical cases to date.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical and/or genetic diagnosis of a rare disease of phosphate metabolism
排除标准
- 未提供
结局指标
主要结局
Prevalence and incidence evaluation
时间窗: Through study completion, an average of 10 years
Evaluation of prevalence and incidence of diseases of phosphate metabolism, globally and for single different disorders
Clinical characterization of diseases of phosphate metabolism
时间窗: Through study completion, an average of 10 years
Detailed clinical characterization of each different rare disease of phosphate metabolism performed through retrospective and prospective cross-sectional and longitudinal collection of available data on disease clinical history, over time clinical manifestations and their age of onset, and related signs and symptoms. For each disease, the collected clinical features will be analyzed through descriptive statistical analyses and expressed as percentage of frequency for categorial data and as mean/median value for continuous data.
Biochemical parameters of phosphate metabolism
时间窗: Through study completion, an average of 10 years
Over time assessment of metabolism of phosphate, in each different rare disease, through the collection of data on specific biochemical parameters, at baseline visit and during follow-ups: * Serum phosphate (mg/dl) * 24h phosphaturia (mg/24h) Each biochemical parameter will be, singularly, categorized as reduced levels, normal levels, or increased levels, according to its reference values, and analyzed through descriptive statistical analyses as percentage of frequency.
Biochemical parameters of kidney function
时间窗: Through study completion, an average of 10 years
Over time assessment of kidney function, in each different rare disease of phosphate metabolism, through the collection of data on specific urinary parameters, at baseline visit and during follow-ups: * Creatinine (mg/dl) * Clearance of creatinine (ml/min) * Estimated Glomerular Filtration Rate (eGFR) (mL/min/1.73 m2) * Spot proteinuria (mg/dl) * 24h proteinuria (mg/24h) Each biochemical parameter will be, singularly, categorized as reduced levels, normal levels, or increased levels, according to its reference values, and analyzed through descriptive statistical analyses as percentage of frequency.
Descriptive analyses of skeletal health and bone fragility in patients with diseases of phosphate metabolism
时间窗: Through study completion, an average of 10 years
Over time assessment of skeletal health and bone fragility: 1. History of fractures, bone deformities, altered musculoskeletal development 2. Calcium and bone metabolism: Calcemia (mg/dl) Calcium ion (mg/dl) 24h calciuria (mg/24h) Parathyroid hormone (pg/ml) 25(OH)-vitamin D (ng/ml) 1,25(OH)2-vitamin D (pg/ml) Bone alkaline phosphatase (mcg/L) Serum carboxy-terminal collagen crosslinks (CTX) (ng/ml) Serum procollagen 1 N-terminal propeptide (P1NP) (ng/ml) 3. Skeleton X-ray: presence/absence of vertebral fracture, osteomalacia, calcinosis, not healing fractures, extra skeletal calcifications 4. Instrumental bone evaluation: bone mineral density (g/cm2), T-scores, Z-scores Biochemical parameters will be categorized as reduced, normal, or increased levels, according to their reference values For each disease, data will be singularly analyzed by descriptive statistical analyses, and expressed as percentage of frequency for categorial data and as mean/median value for continuous data
Assessment of health-related quality of life in patients with a disease of phosphate metabolism
时间窗: Through study completion, an average of 10 years
Self-evaluation of how the disease interferes with quality of life, daily activities, work, and emotional state of the affected patient, through the Short Form Health Survey 36 (SF-36) questionnaire. The SF-36 measures eight scales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). Component analyses measure two distinct concepts: a physical dimension, represented by the Physical Component Summary (PCS), and a mental dimension, represented by the Mental Component Summary (MCS).
Assessment of response to targeted therapy in patients with diseases of phosphate metabolism
时间窗: Through study completion, an average of 10 years
Over time evaluation of the response to therapy in patients with a specific disease of phosphate metabolism for which a targeted therapy for that disease is approved, and who are under treatment independently by the participation to this observational study. Rate of efficacy of each treatment will be assessed among treated patients, by evaluating how medication is able to: 1) control/restore the correct phosphate metabolism over time, 2) alleviate, reduce or eliminate signs and symptoms of the disease, 3) prevent disease progression and/or worsening, 4) ameliorate the quality of life of patient. Side effects and adverse events directly related to each drug, and reported in patient's clinical record, will be evaluated, each, as percentage of frequency.
次要结局
未报告次要终点