3-Week Parathyroid Hormone-related Protein (PTHrP) Dose Escalation Study in Post-Menopausal Women
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|ClinicalTrials.gov Identifier: NCT00222872|
Recruitment Status : Completed
First Posted : September 22, 2005
Last Update Posted : April 28, 2014
|Condition or disease||Intervention/treatment||Phase|
|Osteoporosis Osteoporosis, Postmenopausal||Drug: Parathyroid Hormone-related Protein Drug: Placebo||Phase 1|
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 hormone(1-34) 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 4.7% 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 micrograms/day of PTHrP. 500 micrograms/day 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, i.e., 750, 1000, 1250, and 1500 micrograms. After the first group of 10 successfully receives 500 micrograms/day 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 1,500 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, nausea/vomiting, abdominal or muscle cramps, dizziness/lightheadedness, 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, 1,25 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||61 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||A Three Week Dose Escalation Study of PTHrP(1-36) in Postmenopausal Women|
|Study Start Date :||July 2005|
|Actual Primary Completion Date :||September 2008|
|Actual Study Completion Date :||September 2008|
Active Comparator: 1 - PTHrP Group
Group receiving study drug: PTHrP(1-36)
Drug: Parathyroid Hormone-related Protein
PTHrP(1-36) starting at 500 micrograms, then increasing by 125 micrograms up to a maximum of 1,500 micrograms.
Other Name: study drug
Placebo Comparator: 2 - Single Blind Placebo Group
Receives placebo injections daily via subcutaneous injection
Placebo drug via subcutaneous injection in single blinded fashion daily for 3 weeks
Other Name: Placebo group
- Subjects will receive PTHrP without Dose Limiting Toxicity Events as established by safety parameters consisting of one major criteria or two minor criteria. [ Time Frame: 3 weeks ]
- Efficacy measurements including (but not limited to): measurements of 25-hydroxy vitamin D, 1,25 (OH)2 vitamin D, PTH, PTHrP, osteocalcin, bone specific alkaline phosphatase, procollagen peptide-1, CTx, NTx, IgF and serum DPD. [ Time Frame: 3 week ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00222872
|United States, Pennsylvania|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Mara J. Horwitz, M.D.||University of Pittsburgh|