Ignite Creation Date:
2024-05-06 @ 12:46 AM
Last Modification Date:
2024-10-26 @ 10:54 AM
Study NCT ID:
NCT01652573
Status:
COMPLETED
Last Update Posted:
2017-05-31
First Post:
2012-07-23
Brief Title:
Calcitonin for Treating X-linked Hypophosphatemia
Sponsor:
Yale University
Organization:
Yale University
Study Overview
Official Title:
Calcitonin for Treating X-linked Hypophosphatemia
Status:
COMPLETED
Status Verified Date:
2017-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
X-linked hypophosphatemia XLH is the most common form of inherited rickets in the United States It also causes bone disease in adults XLH is caused by overproduction of a hormone call FGF23 which makes the body waste phosphate This study is designed to determine if nasal calcitonin an already approved drug in the US can lower blood levels of FGF23 and reduce phosphate wasting in patients with XLH In this study the investigators will
1 Determine whether nasal calcitonin significantly lowers integrated 24-hour blood levels of FGF23 in patients with XLH
2 Evaluate whether nasal calcitonin improves serum phosphate levels in XLH
3 Assess whether nasal calcitonin improves blood levels of the active form of vitamin D and calcium absorption from the intestine
4 Make sure that nasal calcitonin is safe and well tolerated
1 Determine whether nasal calcitonin significantly lowers integrated 24-hour blood levels of FGF23 in patients with XLH
2 Evaluate whether nasal calcitonin improves serum phosphate levels in XLH
3 Assess whether nasal calcitonin improves blood levels of the active form of vitamin D and calcium absorption from the intestine
4 Make sure that nasal calcitonin is safe and well tolerated
Detailed Description:
The pathophysiology of X-linked hypophosphatemia XLH was clarified with the report in 1995 by the HYP Consortium led by Dr Michael Econs that mutations in the neutral endopeptidase PHEX are the genetic basis for this disorder Nature Genetics 11130 By a pathway that remains unclear loss-of-function mutations in PHEX lead to elevated circulating levels of FGF23 It is now well established that FGF23 is the proximate biological mediator of this syndrome FGF23 suppresses renal tubular phosphate reabsorption by inhibiting transcription of the major sodium phosphate co-transporters in the proximal renal tubule In addition it suppresses 1-α hydroxylase activity leading low to low-normal serum levels of 125OH2vitamin D This in turn impairs intestinal phosphate and calcium absorption These combined biochemical abnormalities lead to persistent defects in skeletal mineralization manifested as rickets in children and osteomalacia in adults Conventional therapy for XLH consists of oral therapy with phosphate supplements and calcitriol and requires ingestion of medications 4-6 times daily There are several limitations to conventional therapy including its inability to correct growth retardation in children or the enthesopathy so frequently seen in adults Furthermore it is now clear that this therapeutic approach causes a further rise in circulating levels of FGF23 in XLH Thus there is an urgent need for more appropriate therapy directed at the basic pathophysiology of this disorder As detailed in the Research Strategy we have identified calcitonin as a novel suppressor of FGF23 production in XLH A single subcutaneous injection of calcitonin results in a sustained fall in FGF23 levels that persists for 16 hours after drug administration a change not observed in control subjects The fall in serum FGF23 is associated with a rise in serum phosphate and circulating levels of 125OH2vitamin D These data are very exciting as they suggest a novel therapy for XLH This exploratory clinical trial seeks to establish the efficacy of calcitonin in improving the biochemical abnormalities in untreated adults with XLH We will test the hypothesis that calcitonin by lowering circulating levels of FGF23 and raising serum levels of 125OH2vitamin D will improve phosphate homeostasis in patients with XLH To test this hypothesis we will pursue the following specific aims 1 Determine whether 3 months of nasal calcitonin administered at a dose of 400 IUday significantly lowers integrated 24-hour serum levels of FGF23 in patients with XLH 2 Evaluate whether nasal calcitonin improves phosphate homeostasis by raising the TmPGFR and integrated 24 hr serum phosphate concentrations 3 Assess whether nasal calcitonin improves calcium metabolism in patients with XLH by increasing integrated 24 hr serum levels of 125OH2vitamin D and enhancing intestinal calcium absorption as estimated by 24-hour urine calcium 4 Confirm that nasal calcitonin is well tolerated by quantifying side effects and nasal irritation during the trial
If successful this study will provide proof-of-principal for the novel use of an FDA-approved drug in treating XLH This approach unlike conventional treatment addresses the underlying pathophysiology in this disorder and would represent the first therapeutic advance for XLH in 30 years
If successful this study will provide proof-of-principal for the novel use of an FDA-approved drug in treating XLH This approach unlike conventional treatment addresses the underlying pathophysiology in this disorder and would represent the first therapeutic advance for XLH in 30 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R21AR061818 | NIH | None | httpsreporternihgovquickSearchR21AR061818 |