Ignite Creation Date:
2024-05-05 @ 9:19 PM
Last Modification Date:
2024-10-26 @ 10:02 AM
Study NCT ID:
NCT00856401
Status:
UNKNOWN
Last Update Posted:
2018-02-28
First Post:
2009-03-04
Brief Title:
ADD-ON Study to Existing Hypoparathyroidism Studies
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Study Overview
Official Title:
Phase II Trial of Parathyroid Hormone for the Treatment of Hypoparathyroidism
Status:
UNKNOWN
Status Verified Date:
2018-02
Last Known Status:
ACTIVE_NOT_RECRUITING
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:
The purpose of this protocol is to add on additional exploratory studies to investigate changes in bone quality parameters with PTH1-84 treatment of hypoparathyroidism In addition to the biochemical hallmarks of hypoPT it has been found that the microscopic structure of the bone as well as the bone remodeling system are markedly abnormal in this disease How these abnormalities may be corrected with PTH1-84 administration are not fully understood The studies outlined in this add-on protocol are designed to shed light on the mechanistic ways that PTH1-84 replacement may restore normal bone metabolism These mechanistic studies are beyond the scope of the parent NPS study which was designed to assess the safety and efficacy of PTH1-84 in hypoPT treatment Subjects who are participating in the NPS REPLACE RELAY and RACE Studies and the HEXT Study at Columbia University will be invited to participate in this add-on protocol which will involve a separate IRB-approved informed consent
Study procedures
1 High Resolution Peripheral Quantitative Computed Tomography HRpQCT XtremeCT Scanco Done at the same visit as DXA In the REPLACE study twice in RELAY once or not at all if done within the last 6 months in RACE twice and in HEXT three times
2 Osteolineage At BaselineRandomizationVisit One and at 4 8 12 24 and 52 weeks of treatment in the REPLACE RELAY or RACE Study if applicable or at baseline and each 6-months visit in the HEXT Study blood test for circulating osteogenic cells 10 cc will be performed
3 Sclerostin At BaselineRandomizationVisit One and at 4 8 12 24 and 52 weeks of treatment in the REPLACE RELAY or RACE Study if applicable or at baseline and each 6-months visit in the HEXT Study blood test for sclerostin 5cc will be performed
Funding Source - FDA OOPD
Study procedures
1 High Resolution Peripheral Quantitative Computed Tomography HRpQCT XtremeCT Scanco Done at the same visit as DXA In the REPLACE study twice in RELAY once or not at all if done within the last 6 months in RACE twice and in HEXT three times
2 Osteolineage At BaselineRandomizationVisit One and at 4 8 12 24 and 52 weeks of treatment in the REPLACE RELAY or RACE Study if applicable or at baseline and each 6-months visit in the HEXT Study blood test for circulating osteogenic cells 10 cc will be performed
3 Sclerostin At BaselineRandomizationVisit One and at 4 8 12 24 and 52 weeks of treatment in the REPLACE RELAY or RACE Study if applicable or at baseline and each 6-months visit in the HEXT Study blood test for sclerostin 5cc will be performed
Funding Source - FDA OOPD
Detailed Description:
In this protocol we will investigate the mechanisms by which PTH1-84 treatment improves bone quality in patients with hypoparathyroidism Detailed imaging cellular and biochemical studies will be performed on subjects with hypoparathyroidism who are also participating in the NPS Pharmaceutical Companys studies known as REPLACE RELAY RACE studies and IND70449s HEXT Study The parent NPS trial being conducted under NPSs IND 76514 is a multi-site randomized double-blind placebo-controlled trial of PTH1-84 in hypoparathyroidism In the REPLACE Study hypoparathyroid subjects are assigned to either placebo 50 75 or 100 mcg of PTH1-84 a day in a dose-titration design for a 26 week period In RELAY Study hypoparathyroid patients are randomized to 25mcg or 50mcg PTH1-84 for 8 weeks In the RACE Study hypoparathyroid patients utilize 25 50 75 or 100mcg PTH1-84 for 52 weeks The primary efficacy endpoint is a 50 reduction in calcium and calcitriol supplementation The Columbia site is one of the investigative sites for the NPS protocol A letter from NPS accompanying this document certifies that Dr Bilezikian is a subinvestigator in the NPS project
The protocol described in this proposal is different from the NPS study It is being conducted under IND 70449 to Dr Bilezikian It will pursue a number of additional studies that are not being sponsored by NPS or covered by their IND Under IND 70449 assigned to Dr Bilezikian we will investigate the effects of PTH1-84 administration in hypoparathyroidism on bone quality in hypoparathyroidism In addition to the biochemical hallmarks of hypoparathyroidism it has been found that the microarchitectural structure of the bone and the entire bone remodeling system are markedly abnormal in this disease The studies outlined in this add-on protocol are designed to elucidate the specific ways in which PTH1-84 replacement restores to normal bone microstructure and bone metabolism in hypoparathyroidism These mechanistic studies are beyond the scope of the parent NPS study which is designed to assess only the safety and efficacy of PTH1-84 in hypoparathyroidism These special studies are being conducted only by Dr Bilezikians group at Columbia In the summary which is provided here we present the three major studies that will be conducted
PROTOCOL 1 THE EFFECT OF PTH1-84 ADMINISTRATION ON SKELETAL MICROSTRUCTURE AS DETERMINED BY HIGH RESOLUTION IMAGING OF THE SKELETONPERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY HR-PQCT
Protocol For all subjects enrolled at the Columbia site we will perform HR-pQCT Baseline measurement will be obtained twice at Visit 4 of the NPS protocol 2 weeks prior to randomization and at Visit 16 of the NPS protocol the final injection day The reason for the duplicate measurements at each time point is to minimize any variance thus improving the accuracy further of the data to be obtained
Anticipated Results Based upon our preliminary data we expect that the abnormalities that we have observed at baseline in subjects with hypoparathyroidism will be improved by administration of PTH1-84 The improvement in skeletal microstructure will be associated with greater bone strength as determined by finite element analysis and by individual assignment of strength to the specific orientation of trabecular plates and rods in the forearm and the tibia In addition the remarkable abnormalities in cortical structure will be a specific focus of attention particularly in view of the fact that in a disease characterized by excessive secretion of PTH primary hyperparathyroidism cortical thinning is observed Thus with this add-on protocol we will be able to test the hypothesis that PTH regulates the spatial distribution between cortical and trabecular bone This anticipated result will add great value to the protocol and give us insights that would not otherwise be possible to make
PROTOCOL 2 THE EFFECT OF PTH1-84 ADMINISTRATION ON OSTEOBLAST CELLS AS DETERMINED BY MEASUREMENT OF CIRCULATING OSTEOGENIC PRECURSORS
Protocol For all subjects enrolled in the NPS protocol at the Columbia site we will perform measurements of peripheral circulating osteoblast cells The assay will be performed at Visit 5 randomization of the NPS Protocol then again at 4 8 12 and 24 weeks after administration of PTH1-84
Anticipated Results Based upon our preliminary observations we expect that PTH1-84 will stimulate the recruitment in the circulation of cells with an osteoblastic phenotype We expect that PTH1-84 will also stimulate the maturation of cells as defined by ligand markers that can date the chronological age of these cells The ability to demonstrate a specific osteoblastic effect on circulating cells will be correlated with changes in structural parameters to be obtained in these patients using HR-pQCT
PROTOCOL 3 THE EFFECT OF PTH1-84 ADMINISTRATION ON SCLEROSTIN A KEY MEDIATOR OF PTHS OSTEOANABOLIC ACTIONS
Protocol We will measure sclerostin levels at Visit 5 randomization of the NPS Protocol then again at 4 8 12 and 24 weeks post-randomization This will be the first time ever that sclerostin levels will be measured in hypoparathyroid subjects being replaced with PTH1-84
Anticipated Results We expect that the administration of PTH1-84 in subjects with hypoparathyroidism will be associated with acute reductions in sclerostin By virtue of the experimental design of the study we will be able to test further the kinetics of change namely whether the anticipated acute fall in sclerostin levels will be sustained over time The results can be related to the cellular actions of PTH to recruit and to activate the osteogenic cells that will be conducted in Protocol 2 as well as to the osteoanabolic effects we expect to demonstrate in Protocol 1
GENERAL STUDY FEATURES RELATED TO ALL PROTOCOLS
Enrollment and Eligibility Criteria The enrollment criteria follow the protocol being sponsored by the NPS IND They can be provided as an Appendix if requested Study subjects who are enrolled in the NPS study will automatically be eligible for the protocols described above and will constitute the study population for these additional studies We expect to enroll 16 patients for each of the remaining three years of the grant period
Safety Measures The safety measures to be conducted are identical to the NPS protocol sponsored under its IND 76514 They can be provided as an Appendix if requested They have been sent to the office of Dr Mary Parks
Overall Summary and Significance These add-on protocols will be done uniquely at the Columbia site under the sponsorship of IND 70449 assigned to Dr Bilezikian They hold the promise of defining in ways not possible by the standard protocol being sponsored by NPS the mechanisms by which PTH1-84 is therapeutic in subjects with hypoparathyroidism
Funding Source - FDA OOPD
The protocol described in this proposal is different from the NPS study It is being conducted under IND 70449 to Dr Bilezikian It will pursue a number of additional studies that are not being sponsored by NPS or covered by their IND Under IND 70449 assigned to Dr Bilezikian we will investigate the effects of PTH1-84 administration in hypoparathyroidism on bone quality in hypoparathyroidism In addition to the biochemical hallmarks of hypoparathyroidism it has been found that the microarchitectural structure of the bone and the entire bone remodeling system are markedly abnormal in this disease The studies outlined in this add-on protocol are designed to elucidate the specific ways in which PTH1-84 replacement restores to normal bone microstructure and bone metabolism in hypoparathyroidism These mechanistic studies are beyond the scope of the parent NPS study which is designed to assess only the safety and efficacy of PTH1-84 in hypoparathyroidism These special studies are being conducted only by Dr Bilezikians group at Columbia In the summary which is provided here we present the three major studies that will be conducted
PROTOCOL 1 THE EFFECT OF PTH1-84 ADMINISTRATION ON SKELETAL MICROSTRUCTURE AS DETERMINED BY HIGH RESOLUTION IMAGING OF THE SKELETONPERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY HR-PQCT
Protocol For all subjects enrolled at the Columbia site we will perform HR-pQCT Baseline measurement will be obtained twice at Visit 4 of the NPS protocol 2 weeks prior to randomization and at Visit 16 of the NPS protocol the final injection day The reason for the duplicate measurements at each time point is to minimize any variance thus improving the accuracy further of the data to be obtained
Anticipated Results Based upon our preliminary data we expect that the abnormalities that we have observed at baseline in subjects with hypoparathyroidism will be improved by administration of PTH1-84 The improvement in skeletal microstructure will be associated with greater bone strength as determined by finite element analysis and by individual assignment of strength to the specific orientation of trabecular plates and rods in the forearm and the tibia In addition the remarkable abnormalities in cortical structure will be a specific focus of attention particularly in view of the fact that in a disease characterized by excessive secretion of PTH primary hyperparathyroidism cortical thinning is observed Thus with this add-on protocol we will be able to test the hypothesis that PTH regulates the spatial distribution between cortical and trabecular bone This anticipated result will add great value to the protocol and give us insights that would not otherwise be possible to make
PROTOCOL 2 THE EFFECT OF PTH1-84 ADMINISTRATION ON OSTEOBLAST CELLS AS DETERMINED BY MEASUREMENT OF CIRCULATING OSTEOGENIC PRECURSORS
Protocol For all subjects enrolled in the NPS protocol at the Columbia site we will perform measurements of peripheral circulating osteoblast cells The assay will be performed at Visit 5 randomization of the NPS Protocol then again at 4 8 12 and 24 weeks after administration of PTH1-84
Anticipated Results Based upon our preliminary observations we expect that PTH1-84 will stimulate the recruitment in the circulation of cells with an osteoblastic phenotype We expect that PTH1-84 will also stimulate the maturation of cells as defined by ligand markers that can date the chronological age of these cells The ability to demonstrate a specific osteoblastic effect on circulating cells will be correlated with changes in structural parameters to be obtained in these patients using HR-pQCT
PROTOCOL 3 THE EFFECT OF PTH1-84 ADMINISTRATION ON SCLEROSTIN A KEY MEDIATOR OF PTHS OSTEOANABOLIC ACTIONS
Protocol We will measure sclerostin levels at Visit 5 randomization of the NPS Protocol then again at 4 8 12 and 24 weeks post-randomization This will be the first time ever that sclerostin levels will be measured in hypoparathyroid subjects being replaced with PTH1-84
Anticipated Results We expect that the administration of PTH1-84 in subjects with hypoparathyroidism will be associated with acute reductions in sclerostin By virtue of the experimental design of the study we will be able to test further the kinetics of change namely whether the anticipated acute fall in sclerostin levels will be sustained over time The results can be related to the cellular actions of PTH to recruit and to activate the osteogenic cells that will be conducted in Protocol 2 as well as to the osteoanabolic effects we expect to demonstrate in Protocol 1
GENERAL STUDY FEATURES RELATED TO ALL PROTOCOLS
Enrollment and Eligibility Criteria The enrollment criteria follow the protocol being sponsored by the NPS IND They can be provided as an Appendix if requested Study subjects who are enrolled in the NPS study will automatically be eligible for the protocols described above and will constitute the study population for these additional studies We expect to enroll 16 patients for each of the remaining three years of the grant period
Safety Measures The safety measures to be conducted are identical to the NPS protocol sponsored under its IND 76514 They can be provided as an Appendix if requested They have been sent to the office of Dr Mary Parks
Overall Summary and Significance These add-on protocols will be done uniquely at the Columbia site under the sponsorship of IND 70449 assigned to Dr Bilezikian They hold the promise of defining in ways not possible by the standard protocol being sponsored by NPS the mechanisms by which PTH1-84 is therapeutic in subjects with hypoparathyroidism
Funding Source - FDA OOPD
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 |
|---|---|---|---|
| FDA-002525-04A1 | OTHER | FDA - OOPD | None |
| NIH application ID 7566998 | OTHER_GRANT | None | None |
| CFDA 93103 | REGISTRY | None | None |