Ignite Creation Date:
2024-05-05 @ 5:02 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00377312
Status:
COMPLETED
Last Update Posted:
2016-03-22
First Post:
2006-09-14
Brief Title:
7 Day Continuous Parathyroid Hormone IV Infusion
Sponsor:
University of Pittsburgh
Organization:
University of Pittsburgh
Study Overview
Official Title:
Determining the Maximal Safe Dose of a Continuous Infusion of Parathyroid Hormone1-34 Effects on Bone Formation
Status:
COMPLETED
Status Verified Date:
2016-03
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:
Study consists of an eight day inpatient visit on the General Clinical Research Center The investigators specific aims are to
1 To define the maximum safe dose of a seven day continuous administration of parathyroid hormone PTH1-34 in healthy human volunteers
2 To estimate the effect of a seven day continuous administration of parathyroid Hormone PTH in escalating doses on vitamin D metabolism markers of bone turnover and fractional excretion of urine
1 To define the maximum safe dose of a seven day continuous administration of parathyroid hormone PTH1-34 in healthy human volunteers
2 To estimate the effect of a seven day continuous administration of parathyroid Hormone PTH in escalating doses on vitamin D metabolism markers of bone turnover and fractional excretion of urine
Detailed Description:
This study will expand upon earlier infusions studies that demonstrated 1 There is a dose-related increase in 125 OH2 vitamin D in response to PTHrP and PTH over multiple days 2 There is a markedly attenuated vitamin D response to PTHrP compared to PTH particularly during the second 24 hours 3 The increase in 125 OH2 vitamin D is almost certainly responsible for the greater calcemic effect of PTH compared to PTHrP 4 PTHrP is obviously a weaker agonist of 125 OH2 vitamin D but does not result in its suppression as is seen in Humoral Hypercalcemia of Malignancy HHM Thus the suppression of 125 OH2 vitamin D seen in HHM remained unexplained In addition to assessing the effects of an infusion of PTHrP and PTH on calcium handling and 125OH2 vitamin D we also measured their effects on markers of bone turnover Given the clinical observations seen in Hyperparathyroidism HPT and HHM we anticipated that PTH would stimulate both bone resorption and formation while PTHrP would stimulate bone resorption but inhibit formation However we observed that infusions of PTHrP and PTH resulted in an equivalent rapid increase in bone resorption as measured by N-telopeptide NTx and C-telopeptide CTx as well as a progressive decline in bone formation There was no difference between PTH and PTHrP We assumed that formation would ultimately increase with additional time as seen in HPT and therefore examined an additional group of subjects infused with PTHrP for 96 hours However N-terminal propeptide of type 1 procollagen P1NP continued to decline even further as is seen in HHM in contrast to HPT We have not yet studied longer infusions of PTH
One of the reasons for doing this pilot study is to determine the optimal dosing of PTH over a week period of time Intravenous PTH has never been infused into human beings for prolonged periods of time The investigators question whether a prolonged continuous intravenous infusion of PTH will lead to a sustained and progressive suppression of bone formation as occurs in HHM or an increase in bone formation as occurs in HPT They also want to assess the direct influence of long-term continuous PTH infusions on plasma 125 OH2 vitamin D regulation in healthy human volunteers We have shown in our previous studies that doses of 8 picomoles pmolkghr PTH given over 48 hours result in sustained mild serum hypercalcemia with serum calcium seeming to plateau in the range of 11 - 115 mgdL after 48 hours A dose of 8 picomoles pmolkghr has also been shown to cause desirable effects on serum 125OH2 vitamin D and markers of bone turnover and may therefore be the ideal dose However we do not know whether serum calcium will plateau after an infusion of 48 hours with escalating doses or whether it will continue to increase over seven days
To determine what will happen with a prolonged infusion we plan to start with doses lower than 8 picomoles pmolkghr and then gradually increase the dose of PTH in successive groups of subjects In the event of a significant adverse effect immediate action will be taken to reverse it Protocols will be in place to follow in the event of expected adverse events such as hypotension nausea and muscle cramping Severe sudden side effects are not anticipated however mild easily reversible side effects are to be expected as an outcome in order to determine the optimal dose of PTH This study has been approved by the NIH and the Data Safety Monitoring Board DSMB
Seventy five normal healthy men and women will be screened for an eight day in-patient admission to the General Clinical Research Center GCRC Thirty evaluable research participants will receive a seven day infusion of a predetermined dose of PTH Vitals signs blood pressure blood and urine lab results will be monitored frequently as per the study flow sheet The starting dose of PTH 2 picomoles pmolkg will be given to three normal healthy subjects The dose will be escalated in increments with successive groups of three subjects each until early adverse effects mild hypercalcemia postural hypotension tachycardia are seen This dose will then be used in future studies The investigators with this study are trying to discover if a prolonged continuous intravenous infusion of PTH will lead to a sustained and progressive suppression of bone formation as occurs in HHM or an increase in bone formation as occurs in HPT
Subject Population will consist of healthy young adults ages 24-35 years as in our other safety and physiologic studies It is anticipated that we will need to screen 75 subjects in order to obtain 30 evaluable subjects
One of the reasons for doing this pilot study is to determine the optimal dosing of PTH over a week period of time Intravenous PTH has never been infused into human beings for prolonged periods of time The investigators question whether a prolonged continuous intravenous infusion of PTH will lead to a sustained and progressive suppression of bone formation as occurs in HHM or an increase in bone formation as occurs in HPT They also want to assess the direct influence of long-term continuous PTH infusions on plasma 125 OH2 vitamin D regulation in healthy human volunteers We have shown in our previous studies that doses of 8 picomoles pmolkghr PTH given over 48 hours result in sustained mild serum hypercalcemia with serum calcium seeming to plateau in the range of 11 - 115 mgdL after 48 hours A dose of 8 picomoles pmolkghr has also been shown to cause desirable effects on serum 125OH2 vitamin D and markers of bone turnover and may therefore be the ideal dose However we do not know whether serum calcium will plateau after an infusion of 48 hours with escalating doses or whether it will continue to increase over seven days
To determine what will happen with a prolonged infusion we plan to start with doses lower than 8 picomoles pmolkghr and then gradually increase the dose of PTH in successive groups of subjects In the event of a significant adverse effect immediate action will be taken to reverse it Protocols will be in place to follow in the event of expected adverse events such as hypotension nausea and muscle cramping Severe sudden side effects are not anticipated however mild easily reversible side effects are to be expected as an outcome in order to determine the optimal dose of PTH This study has been approved by the NIH and the Data Safety Monitoring Board DSMB
Seventy five normal healthy men and women will be screened for an eight day in-patient admission to the General Clinical Research Center GCRC Thirty evaluable research participants will receive a seven day infusion of a predetermined dose of PTH Vitals signs blood pressure blood and urine lab results will be monitored frequently as per the study flow sheet The starting dose of PTH 2 picomoles pmolkg will be given to three normal healthy subjects The dose will be escalated in increments with successive groups of three subjects each until early adverse effects mild hypercalcemia postural hypotension tachycardia are seen This dose will then be used in future studies The investigators with this study are trying to discover if a prolonged continuous intravenous infusion of PTH will lead to a sustained and progressive suppression of bone formation as occurs in HHM or an increase in bone formation as occurs in HPT
Subject Population will consist of healthy young adults ages 24-35 years as in our other safety and physiologic studies It is anticipated that we will need to screen 75 subjects in order to obtain 30 evaluable subjects
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 |
|---|---|---|---|
| R01DK073039 | NIH | None | httpsreporternihgovquickSearchR01DK073039 |