Ignite Creation Date:
2025-12-25 @ 1:11 AM
Ignite Modification Date:
2025-12-25 @ 11:21 PM
Study NCT ID:
NCT03489993
Status:
COMPLETED
Last Update Posted:
2022-08-05
First Post:
2018-03-29
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D017674', 'term': 'Hypophosphatemia'}, {'id': 'D053098', 'term': 'Familial Hypophosphatemic Rickets'}, {'id': 'D017379', 'term': 'Hypertrophy, Left Ventricular'}], 'ancestors': [{'id': 'D010760', 'term': 'Phosphorus Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D063730', 'term': 'Rickets, Hypophosphatemic'}, {'id': 'D012279', 'term': 'Rickets'}, {'id': 'D001851', 'term': 'Bone Diseases, Metabolic'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D007015', 'term': 'Hypophosphatemia, Familial'}, {'id': 'D015499', 'term': 'Renal Tubular Transport, Inborn Errors'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D008664', 'term': 'Metal Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D002128', 'term': 'Calcium Metabolism Disorders'}, {'id': 'D014808', 'term': 'Vitamin D Deficiency'}, {'id': 'D001361', 'term': 'Avitaminosis'}, {'id': 'D003677', 'term': 'Deficiency Diseases'}, {'id': 'D044342', 'term': 'Malnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D006332', 'term': 'Cardiomegaly'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D006984', 'term': 'Hypertrophy'}, {'id': 'D020763', 'term': 'Pathological Conditions, Anatomical'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Plasma and urine'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 8}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-12-06', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-03', 'completionDateStruct': {'date': '2020-12-23', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-08-04', 'studyFirstSubmitDate': '2018-03-29', 'studyFirstSubmitQcDate': '2018-03-29', 'lastUpdatePostDateStruct': {'date': '2022-08-05', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-04-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-12-23', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Left ventricular hypertrophy', 'timeFrame': '1 year', 'description': 'Higher Ang-(1-7) levels will be associated with a decreased rate of left ventricular hypertrophy'}], 'secondaryOutcomes': [{'measure': 'High blood pressure', 'timeFrame': '1 year', 'description': 'Higher Ang-(1-7) levels will be associated with lower systolic blood pressure'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['FGF23', 'Angiotensin-(1-7)', 'Hypophosphatemia'], 'conditions': ['Hypophosphatemia', 'X-linked Hypophosphatemia', 'Renin-angiotensin System', 'Left Ventricular Hypertrophy']}, 'referencesModule': {'references': [{'pmid': '29250031', 'type': 'BACKGROUND', 'citation': 'Dalton GD, Xie J, An SW, Huang CL. New Insights into the Mechanism of Action of Soluble Klotho. Front Endocrinol (Lausanne). 2017 Nov 17;8:323. doi: 10.3389/fendo.2017.00323. eCollection 2017.'}, {'pmid': '21985788', 'type': 'BACKGROUND', 'citation': 'Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutierrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro-O M, Kusek JW, Keane MG, Wolf M. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011 Nov;121(11):4393-408. doi: 10.1172/JCI46122. Epub 2011 Oct 10.'}, {'pmid': '22034506', 'type': 'BACKGROUND', 'citation': 'Gutierrez OM, Wolf M, Taylor EN. Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study. Clin J Am Soc Nephrol. 2011 Dec;6(12):2871-8. doi: 10.2215/CJN.02740311. Epub 2011 Oct 27.'}, {'pmid': '21673295', 'type': 'BACKGROUND', 'citation': 'Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M; Chronic Renal Insufficiency Cohort (CRIC) Study Group. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011 Jun 15;305(23):2432-9. doi: 10.1001/jama.2011.826.'}, {'pmid': '29381780', 'type': 'BACKGROUND', 'citation': 'Kinoshita Y, Fukumoto S. X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect for New Treatment. Endocr Rev. 2018 Jun 1;39(3):274-291. doi: 10.1210/er.2017-00220.'}, {'pmid': '29025789', 'type': 'BACKGROUND', 'citation': 'Mitsnefes MM, Betoko A, Schneider MF, Salusky IB, Wolf MS, Juppner H, Warady BA, Furth SL, Portale AA. FGF23 and Left Ventricular Hypertrophy in Children with CKD. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):45-52. doi: 10.2215/CJN.02110217. Epub 2017 Oct 12.'}, {'pmid': '23176706', 'type': 'BACKGROUND', 'citation': 'Akimoto T, Yoshizawa H, Watanabe Y, Numata A, Yamazaki T, Takeshima E, Iwazu K, Komada T, Otani N, Morishita Y, Ito C, Shiizaki K, Ando Y, Muto S, Kuro-o M, Kusano E. Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease. BMC Nephrol. 2012 Nov 23;13:155. doi: 10.1186/1471-2369-13-155.'}, {'pmid': '21852584', 'type': 'BACKGROUND', 'citation': 'de Borst MH, Vervloet MG, ter Wee PM, Navis G. Cross talk between the renin-angiotensin-aldosterone system and vitamin D-FGF-23-klotho in chronic kidney disease. J Am Soc Nephrol. 2011 Sep;22(9):1603-9. doi: 10.1681/ASN.2010121251. Epub 2011 Aug 18.'}, {'pmid': '28104822', 'type': 'BACKGROUND', 'citation': 'Drew DA, Katz R, Kritchevsky S, Ix J, Shlipak M, Gutierrez OM, Newman A, Hoofnagle A, Fried L, Semba RD, Sarnak M. Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study. J Am Soc Nephrol. 2017 Jun;28(6):1859-1866. doi: 10.1681/ASN.2016080828. Epub 2017 Jan 19.'}]}, 'descriptionModule': {'briefSummary': "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.\n\nThe 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.\n\nSubjects 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.\n\nThe 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.", 'detailedDescription': "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.\n\nBlood (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.\n\nAll patients receive baseline and, if abnormal, follow-up echocardiograms to evaluate for left ventricular hypertrophy.\n\nBlood 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '24 Years', 'minimumAge': '2 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': "Subjects with hereditary FGF23-related hypophosphatemia will be recruited from the tertiary care Pediatric Endocrinology and Pediatric Nephrology clinics at Brenner Children's Hospital.", 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Confirmed diagnosis of hereditary FGF23-related hypophosphatemia\n\nExclusion Criteria:\n\n* Acquired FGF23-related hypophosphatemia\n* Age less than 2 years\n* Age more than 24 years\n* Inability to provide urine sample'}, 'identificationModule': {'nctId': 'NCT03489993', 'acronym': 'GAP', 'briefTitle': 'FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP)', 'organization': {'class': 'OTHER', 'fullName': 'Wake Forest University Health Sciences'}, 'officialTitle': 'Interplay of FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP)', 'orgStudyIdInfo': {'id': 'IRB00049606'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'FGF23-Related Hypophosphatemic Diseases', 'description': '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).', 'interventionNames': ['Diagnostic Test: Ang II and Ang-(1-7)', 'Diagnostic Test: FGF23 and klotho']}], 'interventions': [{'name': 'Ang II and Ang-(1-7)', 'type': 'DIAGNOSTIC_TEST', 'description': 'Measured in plasma and urine using radioimmunoassays.', 'armGroupLabels': ['FGF23-Related Hypophosphatemic Diseases']}, {'name': 'FGF23 and klotho', 'type': 'DIAGNOSTIC_TEST', 'description': "Measured using ELISA's.", 'armGroupLabels': ['FGF23-Related Hypophosphatemic Diseases']}]}, 'contactsLocationsModule': {'locations': [{'zip': '27157', 'city': 'Winston-Salem', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Wake Forest University Health Sciences', 'geoPoint': {'lat': 36.09986, 'lon': -80.24422}}], 'overallOfficials': [{'name': 'Andrew M South, MD MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Wake Forest University Health Sciences'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Wake Forest University Health Sciences', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}