Autosomal Dominant Hypophosphatemic RicketsNCT02233322
Iron Therapy for Autosomal Dominant Hypophosphatemic Rickets: A Pilot Project.
A study testing Iron in people with Autosomal Dominant Hypophosphatemic Rickets, run by Indiana University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 25 months and older
- Conditions the study is for
- Autosomal Dominant Hypophosphatemic Rickets
- What is being tested?
- Iron
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to 12 Nov 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University School of Medicine
Indianapolis, Indiana, 46202
About this study
Official title: Iron Therapy for Autosomal Dominant Hypophosphatemic Rickets: A Pilot
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.
Read the 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.
- Being tested
- Iron
- Keywords
- ADHR, Rickets, Hypophosphatemia
- Medical subject headings
- Hypophosphatemic Rickets, Autosomal Dominant, Rickets, Hypophosphatemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IronDietary supplement
Also called Ferrous Sulfate, Ferrous Gluconate
All subjects will receive iron supplementation based on iron levels in the blood
| Study group | Role | What they receive |
|---|---|---|
| iron supplements | Experimental | all subjects will receive iron supplementation based on iron levels in blood Receives: Dietary Supplement: Iron |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: FGF23 will be measured at 1, 2, 3, 6, 9, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2014 (estimated)
- Study startAug 2014
- Primary completion12 Nov 2019
- Study completion12 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Autosomal Dominant Hypophosphatemic RicketsStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Econs, Indiana University
- Investigators
- Michael Econs, M.D., Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02233322
- Sponsor's protocol ID
- IRON/ADHR
- Status last verified
- Nov 2019
- First submitted
- 27 Aug 2014
- Last updated
- 14 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
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.
PubMed 11737582Imel 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.
PubMed 17227222Imel 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.
PubMed 21880793Farrow 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.
PubMed 22006328Econs 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.
PubMed 9024275Schouten 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.
PubMed 19151167Schouten 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.
PubMed 19366850Shimizu 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.
PubMed 19555782Bianchine 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.
PubMed 5173181Econs 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.
PubMed 9389727Schwartz 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.
PubMed 19158356Walton 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.
PubMed 50513Ichikawa 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.
PubMed 17710231Imel 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.
PubMed 20157195Imel 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.
PubMed 16551733
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Iron Therapy for Autosomal Dominant Hypophosphatemic Rickets: A Pilot
- ClinicalTrials.gov ID
- NCT02233322
- Acronym / sponsor ID
- IRON/ADHR
- Keywords
- ADHR, Rickets, Hypophosphatemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- 12 Nov 2019 (actual)
- Study completion
- 12 Nov 2019 (actual)
- First posted
- 8 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| iron supplements | Experimental | Dietary Supplement: Ironall subjects will receive iron supplementation based on iron levels in blood |
Who may qualify
- Ages
- 25 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IronAlso: Ferrous Sulfate, Ferrous GluconateAll subjects will receive iron supplementation based on iron levels in the blood | Dietary supplement | iron supplements |
Primary outcome
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
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
- Background: PubMed 11737582White 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.
- Background: PubMed 17227222Imel 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.
- Background: PubMed 21880793Imel 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.
- Background: PubMed 22006328Farrow 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.
- Background: PubMed 9024275Econs 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.
- Background: PubMed 19151167Schouten 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.
- Background: PubMed 19366850Schouten 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.
- Background: PubMed 19555782Shimizu 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.
- Background: PubMed 5173181Bianchine 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.
- Background: PubMed 9389727Econs 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.
- Background: PubMed 19158356Schwartz 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.
- Background: PubMed 50513Walton 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.
- Individual participant dataSharing planned: Yes
Related trials for Autosomal Dominant Hypophosphatemic Rickets
RecruitingObservational study
National Registry of Rare Kidney Diseases
Adenine Phosphoribosyltransferase Deficiency, AH Amyloidosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Econs, M.D. principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Iron in people with Autosomal Dominant Hypophosphatemic Rickets, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02233322, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.