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

Primary Purpose

Autosomal Dominant Hypophosphatemic Rickets

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Iron

About this trial

This is an interventional other trial for Autosomal Dominant Hypophosphatemic Rickets focused on measuring ADHR, Rickets, Hypophosphatemia

Eligibility Criteria

25 Months - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

Indiana University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

iron supplements

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02233322

First Posted

August 27, 2014

Last Updated

November 12, 2019

Sponsor

Indiana University

1. Study Identification

Unique Protocol Identification Number

NCT02233322

Brief Title

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

Official Title

Iron Therapy for Autosomal Dominant Hypophosphatemic Rickets: A Pilot

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

August 2014 (undefined)

Primary Completion Date

November 12, 2019 (Actual)

Study Completion Date

November 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Indiana University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Iron will be provided in an open label treatment to all enrolled subjects. Iron levels will be monitored in blood and doses adjusted with the target of getting the iron levels to or a little above 100 mcg/dl. The study will look to see if there is a decrease of FGF23 level. It will also look at how long does it take to decrease the level of FGF 23 and how long it takes for the serum and urine phosphate to normalize.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autosomal Dominant Hypophosphatemic Rickets

Keywords

ADHR, Rickets, Hypophosphatemia

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

iron supplements

Arm Type

Experimental

Arm Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

Iron

Other Intervention Name(s)

Ferrous Sulfate, Ferrous Gluconate

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Econs, M.D.

Organizational Affiliation

Indiana University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University School of Medicine

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

Citations:

PubMed Identifier

11737582

Citation

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.

Results Reference

background

PubMed Identifier

17227222

Citation

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.

Results Reference

background

PubMed Identifier

21880793

Citation

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.

Results Reference

background

PubMed Identifier

22006328

Citation

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.

Results Reference

background

PubMed Identifier

9024275

Citation

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.

Results Reference

background

PubMed Identifier

19151167

Citation

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.

Results Reference

background

PubMed Identifier

19366850

Citation

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.

Results Reference

background

PubMed Identifier

19555782

Citation

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.

Results Reference

background

PubMed Identifier

5173181

Citation

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.

Results Reference

background

PubMed Identifier

9389727

Citation

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.

Results Reference

background

PubMed Identifier

19158356

Citation

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.

Results Reference

background

PubMed Identifier

50513

Citation

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.

Results Reference

background

PubMed Identifier

17710231

Citation

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.

Results Reference

background

PubMed Identifier

20157195

Citation

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.

Results Reference

background

PubMed Identifier

16551733

Citation

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.

Results Reference

background

Citation

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.

Results Reference

background

Citation

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.

Results Reference

background

PubMed Identifier

11062477

Citation

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

Results Reference

background

PubMed Identifier

31652009

Citation

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.

Results Reference

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

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