Iron Therapy for Autosomal Dominant Hypophosphatemic Rickets: A Pilot Project.

NCT02233322 | Completed DMC

• 1 other identifier: IRON/ADHR
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to gain a better understanding of the effect of iron on fibroblast growth factor 23 (FGF23) in the inherited disorder, autosomal dominant hypophosphatemic rickets (ADHR). ADHR is an inherited disorder in which the body makes too much FGF 23 and causes low blood phosphorus levels and bone problems such as rickets (bowed legs in children) or bone pain and weakness in adults. This study is to test whether or not giving iron helps correct the high FGF23 and there by correcting the phosphate problem.

Conditions

Autosomal Dominant Hypophosphatemic Rickets

Keywords

ADHR; Rickets; Hypophosphatemia

Outcome Measures

Primary Outcomes (1)

• Does increasing serum iron concentrations above 100 mcg/dl in patients with ADHR result in a decrease in intact FGF23.

  Perform a pilot study in ADHR patients with low serum iron concentrations (defined below) to determine if increasing serum iron concentrations above 100 mcg/dl results in a decrease in intact FGF23 (primary endpoint) and C-terminal FGF23 concentrations by at least 20% and normalizes serum phosphorus and TMP/GFR (tubular maximum phosphate reabsorption/ glomerular filtration rate) within 6 months of attaining goal iron concentrations.

  FGF23 will be measured at 1, 2, 3, 6, 9, and 12 months

Study Arms (1)

iron supplements

EXPERIMENTAL

all subjects will receive iron supplementation based on iron levels in blood

Dietary Supplement: Iron

Interventions

Iron DIETARY_SUPPLEMENT

All subjects will receive iron supplementation based on iron levels in the blood

Also known as: Ferrous Sulfate, Ferrous Gluconate

iron supplements

Eligibility Criteria

• Age: 25 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• FGF Mutation in either Arginine 176 or arginine 179
• able and willing to provide consent or have a parent that is able/willing to consent, if a minor
• either serum iron \<50mcg/dl (regardless of phosphate or intact FGF23 concentration); or iron between 500 and 100mcg/dl with serum phosphorus value below 3.0mg/dl for adults or less than or equal to 0.5 mg/dl the lower limit of normal for age in children and intact FGF23 about 30pg/ml
• age \>2 years
• May be receiving treatment with phosphate and calcitriol, but must be willing to undergo dose adjustments by the investigators if iron resolves the phosphate wasting defect.

You may not qualify if:

• malignancy within the last 5 years, except treated squamous or basal cell skin carcinoma
• terminal illness/hospice.
• severe end-organ disease, e.g. cardiovascular, pulmonary, etc, which may limit ability to complete study.
• estimated GFR \<45ml/min/1.73m2, calculated using MDRD formula for adults or modified Schwartz equation for children
• pregnancy or plan on becoming pregnant

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Related Publications (19)

• White KE, Carn G, Lorenz-Depiereux B, Benet-Pages A, Strom TM, Econs MJ. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. Kidney Int. 2001 Dec;60(6):2079-86. doi: 10.1046/j.1523-1755.2001.00064.x.

  PMID: 11737582 BACKGROUND

• Imel EA, Hui SL, Econs MJ. FGF23 concentrations vary with disease status in autosomal dominant hypophosphatemic rickets. J Bone Miner Res. 2007 Apr;22(4):520-6. doi: 10.1359/jbmr.070107.

  PMID: 17227222 BACKGROUND

• Imel EA, Peacock M, Gray AK, Padgett LR, Hui SL, Econs MJ. Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. J Clin Endocrinol Metab. 2011 Nov;96(11):3541-9. doi: 10.1210/jc.2011-1239. Epub 2011 Aug 31.

  PMID: 21880793 BACKGROUND

• Farrow EG, Yu X, Summers LJ, Davis SI, Fleet JC, Allen MR, Robling AG, Stayrook KR, Jideonwo V, Magers MJ, Garringer HJ, Vidal R, Chan RJ, Goodwin CB, Hui SL, Peacock M, White KE. Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):E1146-55. doi: 10.1073/pnas.1110905108. Epub 2011 Oct 17.

  PMID: 22006328 BACKGROUND

• Econs MJ, McEnery PT. Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder. J Clin Endocrinol Metab. 1997 Feb;82(2):674-81. doi: 10.1210/jcem.82.2.3765.

  PMID: 9024275 BACKGROUND

• Schouten BJ, Doogue MP, Soule SG, Hunt PJ. Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalacia. Ann Clin Biochem. 2009 Mar;46(Pt 2):167-9. doi: 10.1258/acb.2008.008151. Epub 2009 Jan 16.

  PMID: 19151167 BACKGROUND

• Schouten BJ, Hunt PJ, Livesey JH, Frampton CM, Soule SG. FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab. 2009 Jul;94(7):2332-7. doi: 10.1210/jc.2008-2396. Epub 2009 Apr 14.

  PMID: 19366850 BACKGROUND

• Shimizu Y, Tada Y, Yamauchi M, Okamoto T, Suzuki H, Ito N, Fukumoto S, Sugimoto T, Fujita T. Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone. 2009 Oct;45(4):814-6. doi: 10.1016/j.bone.2009.06.017. Epub 2009 Jun 23.

  PMID: 19555782 BACKGROUND

• Bianchine JW, Stambler AA, Harrison HE. Familial hypophosphatemic rickets showing autosomal dominant inheritance. Birth Defects Orig Artic Ser. 1971 May;7(6):287-95. No abstract available.

  PMID: 5173181 BACKGROUND

• Econs MJ, McEnery PT, Lennon F, Speer MC. Autosomal dominant hypophosphatemic rickets is linked to chromosome 12p13. J Clin Invest. 1997 Dec 1;100(11):2653-7. doi: 10.1172/JCI119809.

  PMID: 9389727 BACKGROUND

• Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009 Mar;20(3):629-37. doi: 10.1681/ASN.2008030287. Epub 2009 Jan 21.

  PMID: 19158356 BACKGROUND

• Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration. Lancet. 1975 Aug 16;2(7929):309-10. doi: 10.1016/s0140-6736(75)92736-1. No abstract available.

  PMID: 50513 BACKGROUND

• Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, Goetz R, Mohammadi M, White KE, Econs MJ. A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest. 2007 Sep;117(9):2684-91. doi: 10.1172/JCI31330.

  PMID: 17710231 BACKGROUND

• Imel EA, DiMeglio LA, Hui SL, Carpenter TO, Econs MJ. Treatment of X-linked hypophosphatemia with calcitriol and phosphate increases circulating fibroblast growth factor 23 concentrations. J Clin Endocrinol Metab. 2010 Apr;95(4):1846-50. doi: 10.1210/jc.2009-1671. Epub 2010 Feb 15.

  PMID: 20157195 BACKGROUND

• Imel EA, Peacock M, Pitukcheewanont P, Heller HJ, Ward LM, Shulman D, Kassem M, Rackoff P, Zimering M, Dalkin A, Drobny E, Colussi G, Shaker JL, Hoogendoorn EH, Hui SL, Econs MJ. Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia. J Clin Endocrinol Metab. 2006 Jun;91(6):2055-61. doi: 10.1210/jc.2005-2105. Epub 2006 Mar 21.

  PMID: 16551733 BACKGROUND

• Sabbagh, Y., Tenenhouse HS, Econs, MJ, Mendelian Hypophosphatemias, in The Metabolic and Molecular Basis of Inherited Disease, C.R.S.e. al, Editor. 2008, McGraw-Hill: New York.

  BACKGROUND

• White, K.E. and M.J. Econs, Fibroblast growth factor-23 (FGF23), in Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 2013, Wiley-Blackwell. p. 188-194.

  BACKGROUND

• ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000 Nov;26(3):345-8. doi: 10.1038/81664.

  PMID: 11062477 BACKGROUND

• Imel EA, Liu Z, Coffman M, Acton D, Mehta R, Econs MJ. Oral Iron Replacement Normalizes Fibroblast Growth Factor 23 in Iron-Deficient Patients With Autosomal Dominant Hypophosphatemic Rickets. J Bone Miner Res. 2020 Feb;35(2):231-238. doi: 10.1002/jbmr.3878. Epub 2019 Oct 25.

  PMID: 31652009 DERIVED

MeSH Terms

Conditions

Hypophosphatemic Rickets, Autosomal Dominant; Rickets; Hypophosphatemia

Interventions

Iron; ferrous sulfate; ferrous gluconate

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Phosphorus Metabolism Disorders

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Michael Econs, M.D.

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Endocrinology and Metabolism

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: September 8, 2014
• Study Start: August 1, 2014
• Primary Completion: November 12, 2019
• Study Completion: November 12, 2019
• Last Updated: November 14, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)