An observational study in Hypophosphatemia, X-linked Hypophosphatemia and Renin-angiotensin System, sponsored by Wake Forest University Health Sciences. Completed at 1 site in United States. Open to participants aged 2 Years to 24 Years. Per ClinicalTrials.gov, last updated 2022-08-05.
Sponsored by Wake Forest University Health Sciences · Observational
Hereditary hypophosphatemia encompasses rare genetic conditions characterized by renal phosphate wasting. Increased circulating levels of fibroblast growth factor 23 (FGF23), a key regulator of phosphorus metabolism, are critical to the pathophysiology of these diseases, most notably in X-linked hypophosphatemia (XLH). Increased FGF23 induces hypertrophy and scarring in the heart in part via stimulating the traditional renin-angiotensin system (RAS) pathway, angiotensin-converting enzyme (ACE)/angiotensin (Ang ll), particularly in patients with chronic kidney disease, but the effect of FGF23 on the heart in patients with FGF23-related hypophosphatemic diseases is unknown. In addition, the relationship between FGF23 and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7) pathway of the RAS is unknown.
The objective of this study is to describe the relationship between FGF23, which causes low phosphorus levels, and components of the RAS in the blood and urine to help the investigators understand why the disease occurs and how to better treat it.
Subjects will be identified by querying the Electronic Medical Record according to medical diagnosis. Thirty subjects, 2-24 years of age, will be recruited from the tertiary care Pediatric Endocrinology and Pediatric Nephrology clinics at Brenner Children's Hospital. Inclusion criteria include a confirmed diagnosis of hereditary FGF23-related hypophosphatemia. Clinical data will be obtained from the Electronic Medical Record. Each subject will undergo study assessments at baseline, 6 months and 1 year that include blood work, an echocardiogram, and blood pressure measurements.
The primary hypothesis is that subjects with higher Ang-(1-7) levels have lower rates of cardiac hypertrophy and thus are protected against high FGF23 levels. The secondary hypothesis is that subjects with higher Ang-(1-7) levels have lower systolic blood pressure.
Clinical data will be collected from the Electronic Medical Record, including age, sex, parent-reported race, past medical and family histories, and current medications. The investigators will calculate body mass index and define overweight/obesity as a body mass index ≥85% percentile for age and sex. The investigators will calculate the estimated glomerular filtration rate to measure renal function based on serum creatinine standardized to age, sex, and height.
Blood (less than 5 mL) and urine samples will be collected at each study visit at the same time as routine clinical labs. Ang ll and Ang-(1-7) will be measured in the plasma and urine using radioimmunoassays in a CLIA-certified laboratory within the Hypertension and Vascular Research Biomarker Analytical Core at Wake Forest School of Medicine. The investigators will calculate the ratio of the two peptides and, in the urine, standardize their values to urine creatinine. In the blood, creatinine, calcium, phosphorus, and vitamin D will be collected and in the urine, albumin, calcium, phosphorus, and creatinine will be collected all per standard of care. FGF23 and klotho will be analyzed in the Core via commercially available ELISA's.
All patients receive baseline and, if abnormal, follow-up echocardiograms to evaluate for left ventricular hypertrophy.
Blood pressure will be measured at clinic visits. Because age, sex, and height define normative pediatric values, the investigators will standardize blood pressure with z scores.
49 studies on the registry are indexed under Familial Hypophosphatemic Rickets; 8 are open to participants now.
This study's enrollment of 8 is below the median of 50 across 16 observational studies indexed under Familial Hypophosphatemic Rickets.
Browse Familial Hypophosphatemic Rickets studies →Wake Forest University Health Sciences is the lead sponsor of 1,351 studies on the registry; 201 are open to participants now.
Of its 332 completed or terminated interventional studies of FDA-regulated products, 251 (76%) have results posted.
Compared within Familial Hypophosphatemic Rickets, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Hypophosphatemia. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Subjects with hereditary FGF23-related hypophosphatemia will be recruited from the tertiary care Pediatric Endocrinology and Pediatric Nephrology clinics at Brenner Children's Hospital.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
The diagnostic tests Ang II, Ang-(1-7), FGF23, and klotho will be measured in the cohort. Patients in the cohort will have the diseases X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets type 1 (ARHR1), autosomal recessive hypophosphatemic rickets type 2 (ARHR2), osteoglophonic dysplasia, Jansen-type metaphyseal chondrodysplasia, Raine syndrome, McCune-Alright syndrome, and epidermal nevus syndrome (ENS).
Diagnostic Test: Ang II and Ang-(1-7) · Diagnostic Test: FGF23 and klotho
Measured in plasma and urine using radioimmunoassays.
Measured using ELISA's.
Left ventricular hypertrophy
Higher Ang-(1-7) levels will be associated with a decreased rate of left ventricular hypertrophy
Time frame: 1 year
High blood pressure
Higher Ang-(1-7) levels will be associated with lower systolic blood pressure
Time frame: 1 year
Plan to share: No
This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.
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