<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02233322</url>
  </required_header>
  <id_info>
    <org_study_id>IRON/ADHR</org_study_id>
    <nct_id>NCT02233322</nct_id>
  </id_info>
  <brief_title>Iron Therapy for Autosomal Dominant Hypophosphatemic Rickets: A Pilot Project.</brief_title>
  <official_title>Iron Therapy for Autosomal Dominant Hypophosphatemic Rickets: A Pilot</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to gain a better understanding of the effect of iron on&#xD;
      fibroblast growth factor 23 (FGF23) in the inherited disorder, autosomal dominant&#xD;
      hypophosphatemic rickets (ADHR). ADHR is an inherited disorder in which the body makes too&#xD;
      much FGF 23 and causes low blood phosphorus levels and bone problems such as rickets (bowed&#xD;
      legs in children) or bone pain and weakness in adults. This study is to test whether or not&#xD;
      giving iron helps correct the high FGF23 and there by correcting the phosphate problem.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Iron will be provided in an open label treatment to all enrolled subjects. Iron levels will&#xD;
      be monitored in blood and doses adjusted with the target of getting the iron levels to or a&#xD;
      little above 100 mcg/dl.&#xD;
&#xD;
      The study will look to see if there is a decrease of FGF23 level. It will also look at how&#xD;
      long does it take to decrease the level of FGF 23 and how long it takes for the serum and&#xD;
      urine phosphate to normalize.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">November 12, 2019</completion_date>
  <primary_completion_date type="Actual">November 12, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Does increasing serum iron concentrations above 100 mcg/dl in patients with ADHR result in a decrease in intact FGF23.</measure>
    <time_frame>FGF23 will be measured at 1, 2, 3, 6, 9, and 12 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Autosomal Dominant Hypophosphatemic Rickets</condition>
  <arm_group>
    <arm_group_label>iron supplements</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>all subjects will receive iron supplementation based on iron levels in blood</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Iron</intervention_name>
    <description>All subjects will receive iron supplementation based on iron levels in the blood</description>
    <arm_group_label>iron supplements</arm_group_label>
    <other_name>Ferrous Sulfate</other_name>
    <other_name>Ferrous Gluconate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  FGF Mutation in either Arginine 176 or arginine 179&#xD;
&#xD;
          -  able and willing to provide consent or have a parent that is able/willing to consent,&#xD;
             if a minor&#xD;
&#xD;
          -  either serum iron &lt;50mcg/dl (regardless of phosphate or intact FGF23 concentration);&#xD;
             or iron between 500 and 100mcg/dl with serum phosphorus value below 3.0mg/dl for&#xD;
             adults or less than or equal to 0.5 mg/dl the lower limit of normal for age in&#xD;
             children and intact FGF23 about 30pg/ml&#xD;
&#xD;
          -  age &gt;2 years&#xD;
&#xD;
          -  May be receiving treatment with phosphate and calcitriol, but must be willing to&#xD;
             undergo dose adjustments by the investigators if iron resolves the phosphate wasting&#xD;
             defect.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  malignancy within the last 5 years, except treated squamous or basal cell skin&#xD;
             carcinoma&#xD;
&#xD;
          -  terminal illness/hospice.&#xD;
&#xD;
          -  severe end-organ disease, e.g. cardiovascular, pulmonary, etc, which may limit ability&#xD;
             to complete study.&#xD;
&#xD;
        estimated GFR &lt;45ml/min/1.73m2, calculated using MDRD formula for adults or modified&#xD;
        Schwartz equation for children&#xD;
&#xD;
          -  pregnancy or plan on becoming pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Econs, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Indiana University School of Medicine</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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.</citation>
    <PMID>11737582</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>17227222</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21880793</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>22006328</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>9024275</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19151167</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19366850</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19555782</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>5173181</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>9389727</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>19158356</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>50513</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>17710231</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20157195</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>16551733</PMID>
  </reference>
  <reference>
    <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.</citation>
  </reference>
  <reference>
    <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.</citation>
  </reference>
  <reference>
    <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.</citation>
    <PMID>11062477</PMID>
  </reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 8, 2014</study_first_posted>
  <last_update_submitted>November 12, 2019</last_update_submitted>
  <last_update_submitted_qc>November 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Michael Econs</investigator_full_name>
    <investigator_title>Professor of Endocrinology and Metabolism</investigator_title>
  </responsible_party>
  <keyword>ADHR</keyword>
  <keyword>Rickets</keyword>
  <keyword>Hypophosphatemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthrogryposis</mesh_term>
    <mesh_term>Rickets</mesh_term>
    <mesh_term>Rickets, Hypophosphatemic</mesh_term>
    <mesh_term>Familial Hypophosphatemic Rickets</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ferrous gluconate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02233322
org study id: IRON/ADHR
nct id: NCT02233322
lead sponsor: 
has dmc: Yes
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Does increasing serum iron concentrations above 100 mcg/dl in patients with ADHR result in a decrease in intact FGF23.
time frame: FGF23 will be measured at 1, 2, 3, 6, 9, and 12 months
description: 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.
arm group label: iron supplements
arm group type: Experimental
description: all subjects will receive iron supplementation based on iron levels in blood
intervention type: Dietary Supplement
intervention name: Iron
description: All subjects will receive iron supplementation based on iron levels in the blood
arm group label: iron supplements
other name: Ferrous Sulfate
other name: Ferrous Gluconate
criteria: 
gender: All
minimum age: 25 Months
maximum age: N/A
healthy volunteers: No
last name: Michael Econs, M.D.
role: Principal Investigator
affiliation: Indiana University School of Medicine
facility: 
country: United States
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.
PMID: 11737582
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.
PMID: 17227222
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.
PMID: 21880793
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.
PMID: 22006328
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.
PMID: 9024275
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.
PMID: 19151167
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.
PMID: 19366850
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.
PMID: 19555782
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.
PMID: 5173181
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.
PMID: 9389727
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.
PMID: 19158356
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.
PMID: 50513
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.
PMID: 17710231
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.
PMID: 20157195
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.
PMID: 16551733
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.
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.
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.
PMID: 11062477
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: Michael Econs
investigator title: Professor of Endocrinology and Metabolism
mesh term: Arthrogryposis
mesh term: Rickets
mesh term: Rickets, Hypophosphatemic
mesh term: Familial Hypophosphatemic Rickets
mesh term: Ferrous gluconate
sharing ipd: Yes