Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00222872
Status:
COMPLETED
Last Update Posted:
2014-04-28
First Post:
2005-09-09
Brief Title:
3-Week Parathyroid Hormone-related Protein PTHrP Dose Escalation Study in Post-Menopausal Women
Sponsor:
University of Pittsburgh
Organization:
University of Pittsburgh
Study Overview
Official Title:
A Three Week Dose Escalation Study of PTHrP1-36 in Postmenopausal Women
Status:
COMPLETED
Status Verified Date:
2014-04
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:
The main purpose of this study is to determine the safety and effectiveness of three week daily subcutaneous injections of Parathyroid Hormone-related Protein 1-36 Previous studies indicated that PTHrP has a skeletal anabolic or bone-building effect and has shown to increase bone mineral density in postmenopausal women with osteoporosis Safety of PTHrP will be determined by measurements of blood pressure and pulse serum blood calcium levels and subjective symptoms Effectiveness will be measured by changes in measurements of blood and urine markers of bone turnover
Detailed Description:
Parathyroid Hormone-related Protein 1-36 or PTHrP is a neuroendocrine peptide which shares significant homology with the only currently FDA approved anabolic agent for the treatment of osteoporosis parathyroid hormone1-34 or PTH PTH when given alone has shown to increase lumbar spine bone mass by 12-15 over a 2-3 year period
Previous studies indicate PTHrP may have a pure anabolic effect on bone Postmenopausal women taking estrogen with osteoporosis who received daily subcutaneous PTHrP for 3 months exhibited a 47 increase in bone mineral density compared to those taking placebo There were no side effects associated with PTHrP despite the fact that the doses given were 20 times the usual doses of PTH In another study young healthy volunteers received a single one-time subcutaneous doses of PTHrP in amounts up to 2 mg without any dose limiting toxicities
This study will directly compare the effect of placebo and escalating doses of PTHrP given subcutaneously to postmenopausal women for three weeks Each subject will have four outpatient visits and one inpatient 24-hour visit on the last day 20 women in phase I will receive either placebo or 500 microgramsday of PTHrP 500 microgramsday was selected as the lowest dose because it is similar to the dose used in our previous 3 month placebo controlled study In Phase II the doses of PTHrP will be increased in increments of approximately 30 for each successive group ie 750 1000 1250 and 1500 micrograms After the first group of 10 successfully receives 500 microgramsday for 21 days increased doses will be given to groups of three subjects until evidence of dose limiting toxicity DLT occurs or a maximum dose of 1500 micrograms is reached Dose limiting toxicities are specified in the protocol and comprise either one major criteria hypotension orthostatic hypotension tachycardia hypertension hypercalcemia or hypophosphatemia or two minor criteria flushing nauseavomiting abdominal or muscle cramps dizzinesslightheadedness palpitations or any other unpleasant subjective symptom
If a particular dose of PTHrP causes a dose-limiting toxicity the immediately preceding lower dose will be defined as the maximum safely tolerated dose Once the maximum safely tolerated dose is determined it will be given to a total of ten healthy subjects to ensure that is is safe and well tolerated
Study methods include outpatient visits on days 1 5 10 15 and an in-patient visit on day 21 for lab collection and patient examination Blood and urine safety labs consist of serum ionized calcium total calcium creatinine phosphorus and albumin Efficacy labs consist of urine and blood measurements of 25-hydroxy vitamin D 125 vitamin D PTH osteocalcin bone specific alkaline phosphatase procollagen peptide-1 C-telopeptide CTx N-telopeptide NTx Insulin-like growth factors IgF and serum free deoxypyridinoline DPD
Subject population includes up to 48 healthy 50-75 year old postmenopausal women who are Caucasian Asian and Hispanic African-Americans are excluded from the study since it is well documented that African-Americans have clear quantitative differences in bone density and sensitivity to parathyroid hormone No bone densitometry scans are done during this study
Previous studies indicate PTHrP may have a pure anabolic effect on bone Postmenopausal women taking estrogen with osteoporosis who received daily subcutaneous PTHrP for 3 months exhibited a 47 increase in bone mineral density compared to those taking placebo There were no side effects associated with PTHrP despite the fact that the doses given were 20 times the usual doses of PTH In another study young healthy volunteers received a single one-time subcutaneous doses of PTHrP in amounts up to 2 mg without any dose limiting toxicities
This study will directly compare the effect of placebo and escalating doses of PTHrP given subcutaneously to postmenopausal women for three weeks Each subject will have four outpatient visits and one inpatient 24-hour visit on the last day 20 women in phase I will receive either placebo or 500 microgramsday of PTHrP 500 microgramsday was selected as the lowest dose because it is similar to the dose used in our previous 3 month placebo controlled study In Phase II the doses of PTHrP will be increased in increments of approximately 30 for each successive group ie 750 1000 1250 and 1500 micrograms After the first group of 10 successfully receives 500 microgramsday for 21 days increased doses will be given to groups of three subjects until evidence of dose limiting toxicity DLT occurs or a maximum dose of 1500 micrograms is reached Dose limiting toxicities are specified in the protocol and comprise either one major criteria hypotension orthostatic hypotension tachycardia hypertension hypercalcemia or hypophosphatemia or two minor criteria flushing nauseavomiting abdominal or muscle cramps dizzinesslightheadedness palpitations or any other unpleasant subjective symptom
If a particular dose of PTHrP causes a dose-limiting toxicity the immediately preceding lower dose will be defined as the maximum safely tolerated dose Once the maximum safely tolerated dose is determined it will be given to a total of ten healthy subjects to ensure that is is safe and well tolerated
Study methods include outpatient visits on days 1 5 10 15 and an in-patient visit on day 21 for lab collection and patient examination Blood and urine safety labs consist of serum ionized calcium total calcium creatinine phosphorus and albumin Efficacy labs consist of urine and blood measurements of 25-hydroxy vitamin D 125 vitamin D PTH osteocalcin bone specific alkaline phosphatase procollagen peptide-1 C-telopeptide CTx N-telopeptide NTx Insulin-like growth factors IgF and serum free deoxypyridinoline DPD
Subject population includes up to 48 healthy 50-75 year old postmenopausal women who are Caucasian Asian and Hispanic African-Americans are excluded from the study since it is well documented that African-Americans have clear quantitative differences in bone density and sensitivity to parathyroid hormone No bone densitometry scans are done during this study
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 |
|---|---|---|---|
| NIH RO - DK 51081 | None | None | None |