Institution of an Italian Multicenter Database of Patients Affected by Diseases of Phosphate Metabolism

Condition(s) studied

Study summary

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:

1. Evaluation of prevalence and incidence of diseases of phosphate metabolism in Italy, globally and for single different disorders
2. 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
3. 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
4. Self-evaluation of health-related quality of life in patients with a disease of phosphate metabolism
5. 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.

Eligibility

Primary outcome measure(s)

• Prevalence and incidence evaluation — 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 — 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 — 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 — 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 — 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 — 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 — 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.

Trial sites (28)

More F.I.R.M.O. - Fondazione Italiana Ricerca sulle Malattie dell'Osso - Ente del Terzo Settore trials in Italy