OsteoporosisPhase 2NCT00853723
Comparison Study of PTHrP and PTH to Treat Osteoporosis
A Phase 2 study testing Parathyroid hormone related protein (1-36), Parathyroid hormone related protein(1-36) and Parathyroid hormone (1-34) in people with Osteoporosis, run by University of Pittsburgh at 1 site in United States.
Trial summary
This is a three month comparison trial of standard dose parathyroid hormone (PTH) (1-34) and two different doses of Parathyroid Hormone-related Protein (PTHrP) (1-36). The investigators want to to demonstrate that daily subcutaneous injection of PTHrP (1-36) in postmenopausal women with osteoporosis stimulates bone… Read more about this study
- Who is it for?
- Ages 45 to 75 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Parathyroid hormone related protein (1-36), Parathyroid hormone related protein(1-36) and Parathyroid hormone (1-34)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to Jun 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 45 - 75 year old Caucasian, Hispanic or Asian women
- one year post-menopausal if older than 50 years
- three years post-menopausal if between the ages of 45 - 50 years
- body mass index less than or equal to 30
- T-scores on screening Dual X-Ray Absorbiometry (DXA) scan between - 2.0 to - 4.5 of lumbar spine or hip
- have at lease two spinal vertebrae evaluable by DXA analysis
Who cannot join
- bisphosphonate therapy within the last two years
- estrogen replacement hormones or SERMS within last one year
- no more than one week of PTHrP, PTH, or an analog of PTH within the last year
- an atraumatic bone fracture within the last 6 months
- significant or active diseases of any organ system
- history of malignancy
Show all 12Show fewer
- anemia with a hematocrit less than 34%
- significant drug or alcohol abuse
- having received any investigational drug within the last 90 days
- taking any medication that may interfere with skeletal metabolism, such as phenobarbital, dilantin, glucocorticoids, and hydrochlorathiazide
- abnormal screening labs including serum Ca greater than 10.5 g/dl, 25 hydroxy vitamin D less than 20 ng/ml or PTH greater than 65 pg/ml
- African-Americans for this particular study - although future studies are planned
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Clinical & Translational Research Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Comparison of 3 Month PTHrP(1-36) and PTH(1-34) on Post-Menopausal Osteoporosis
This is a three month comparison trial of standard dose parathyroid hormone (PTH) (1-34) and two different doses of Parathyroid Hormone-related Protein (PTHrP) (1-36). The investigators want to to demonstrate that daily subcutaneous injection of PTHrP (1-36) in postmenopausal women with osteoporosis stimulates bone formation to the same or greater degree than PTH (1-34) but with less bone resorption.
Read the detailed description
Osteoporosis is a metabolic bone disease characterized by low bone mass and structural deterioration of bone tissue. It results from failure of osteoblasts to form sufficient new bone, from an excessive rate of osteoclastic bone resorption, or from the combination of both processes. The resultant bone fragility leads to an increased susceptibility to fractures, especially of the hip, spine and wrist. There is an increased mortality rate following both hip and vertebral fractures, and the presence of one fracture is a potent risk factor for future fractures. This leads to a decline in the quality of life and an associated loss of independence among the millions of individuals in the United States and worldwide afflicted with the disease. There is an additional population at an increased risk for fractures due to a less severe loss of bone mass, known as osteopenia (1). Already ten million individuals in the United States are estimated to have the disease and thirty four million more are at increased risk due to low bone mass (1).
Approved pharmacological treatments for postmenopausal osteoporosis include two classes of drugs: the antiresorptive and the anabolics (2). The antiresorptive include estrogen, calcitonin, selective estrogen receptor modulators, and bisphosphonates. The antiresorptive medications prevent bone loss by inhibiting both osteoclastic bone resorption and formation, by slowing bone turnover, and by allowing for increased mineralization of osteoid (2). The increase in bone mineral density from the antiresorptive agents is generally reported to be in the range of 2-8% over 1-7 years (3-7).
There is only one anabolic agent that is presently approved by the FDA for treatment for osteoporosis: parathyroid hormone, PTH (1-34), or teriparatide. PTH(1-34) was approved by the FDA in 2002 and it acts by increasing bone density by stimulating the PTH-1 receptor. This induces an increase in osteoblast mediated bone formation and osteoclast mediated bone resorption. Daily subcutaneous PTH is anabolic as there is stimulation of bone formation to a greater extent than bone resorption. The overall net result of biosynthetic PTH (1-34) is an increase in bone mineral density and a decrease in fractures (8). Daily PTH(1-34) treatment has been shown to effectively reduce the risk of both vertebral and nonvertebral fractures. Measurements of bone mineral density (BMD) of the lumbar spine (LS) resulted in an increase in bone density of 9 percent when compared to placebo (9). A daily 20 microgram dose of subcutaneous PTH(1-34) reduced the risk of getting two or more vertebral fractures by 77%, and the risk of at least one moderate or severe fracture was reduced by 90 and 78% respectively (9). Additionally, one vertebral fracture was prevented for every 12 patient years of treatment, and women were 35% less likely to have one or more new nonvertebral fragility fractures (9).
Parathyroid hormone-related protein or PTHrP is a protein peptide that was first isolated in 1987 as the factor responsible for the syndrome of humoral hypercalcemia of malignancy (HHM) (10-14). PTHrP is found in almost every tissue and cell type in the body, and appears to regulate cellular proliferation, survival, and differentiation in normal tissue as well as in malignancies (15-16). As the name implies, PTHrP is similar to PTH. Both peptides bind to the same receptor, PTH-1 R, and activate downstream signaling pathways causing similar post receptor effects (17).
Since PTH is a potent anabolic agent, we hypothesize that PTHrP may act in an anabolic fashion as well. We are seeking to demonstrate in this study that PTHrP acts as an anabolic agent in the treatment of osteoporosis with similar or better efficacy than PTH in respect to bone formation but with less bone resorption and fewer side effects, such as hypercalcemia.
The current studies are a sequel to initial phase 1 trials assessing the efficacy and safety of daily subcutaneous injection of PTHrP on the human skeleton. Previous studies have demonstrated that a single daily injection of ~ 400 mcg/day of PTHrP (1-36) in postmenopausal women on estrogen with osteoporosis led to a 4.7% increase in lumbar spine bone mineral density (BMD) after three months and all subjects were free of hypercalcemia or other adverse effects (18). In contrast with PTH, the doses of PTHrP are much larger, yet well-tolerated, and the increments in spine BMD are large and rapid with some subjects showing increases in spine BMD of 6-8% in as soon as three months in studies done thus far (18). PTHrP appears to selectively stimulate bone formation without stimulating bone resorption (18). This exciting observation may point towards PTHrP being a pure skeletal anabolic agent (21). Preliminary data analysis from a more recent three week dose escalation trial indicates demonstrates that the dose of 500 mcg/day of PTHrP causes 38% increase in P1NP and a 20% decrease in CTX indicating far greater bone formation than bone resorption with no hypercalcemia. At 625 mcg/day there were similar increases in P1NP with hypercalcemia in only 10% of subjects and hypercalcuria in 20%. In contrast in subjects receiving 750 mcg/day 50% developed hypercalcemia requiring early termination. The P1NP and CTX data from the three week dose escalation trial was used for both determining dose and sample size calculations for this study.
- Conditions
- Osteoporosis
- Being tested
- Parathyroid hormone related protein (1-36), Parathyroid hormone related protein(1-36), Parathyroid hormone (1-34)
- Keywords
- osteoporosis, post-menopausal, bone anabolic agents
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parathyroid hormone related protein (1-36)Drug
Also called PTHrP (1-36), PTHrP
PTHrP (1-36) 400 micrograms / day administered subcutaneously for 3 months
Parathyroid hormone related protein(1-36)Drug
Also called PTHrP (1-36), PTHrP
PTHrP(1-36)600 micrograms subcutaneously administered daily for 3 months
Parathyroid hormone (1-34)Drug
Also called PTH(1-34), Teriparatide (brand name: Forteo)
PTH(1-34)20 micrograms subcutaneously administered daily for 3 months
| Study group | Role | What they receive |
|---|---|---|
| PTHrP 400 mcg/day | Experimental | Post-menopausal women with osteoporosis will subcutaneously administer PTHrP 400 micrograms daily for three months. Receives: Drug: Parathyroid hormone related protein (1-36) |
| PTHrP 600 mcg/day | Experimental | Post-menopausal women with osteoporosis will subcutaneously administer PTHrP 600 micrograms daily for three months. Receives: Drug: Parathyroid hormone related protein(1-36) |
| PTH 20 mcg/day | Active comparator | Post-menopausal women with osteoporosis will subcutaneously administer the FDA approved dose of PTH 20 micrograms daily for three months. Receives: Drug: Parathyroid hormone (1-34) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Procallagen-1 Amino-terminal Peptide (P1NP)
Measured: Baseline, Day 15, Day 30, Day 60, Day 90
Carboxy-terminal Telopeptides of Collagen-1 (CTX)
Measured: Baseline, Day 15, Day 30, Day 60, Day 90
Secondary outcomes (11)
Changes in Bone Mineral Density of the Lumbar Spine.
Measured: 90 days
Changes in Bone Mineral Density of the Total Hip.
Measured: 90 days
Changes in Bone Mineral Density of the Femoral Neck.
Measured: 90 days
Changes in Bone Mineral Density of the Forearm.
Measured: 90 days
Changes in Bone Mineral Density of the Distal 1/3 Radius.
Measured: 90 days
Total Serum Calcium (mg/dl)
Measured: Baseline, Day 15, Day 30, Day 60, Day 90
Serum Phosphorous
Measured: Baseline, Day 15, Day 30, Day 60, Day 90
24 Hour Urine Calcium
Measured: 90 days
1,25 Vitamin D
Measured: Baseline, Day 15, Day 30, Day 60, Day 90
Fractional Excretion of Calcium
(Serum Creatinine X Urine Calcium)/(Serum Calcium X Urine Creatinine)
Measured: Baseline, Day 15, Day 30, Day 60, Day 90
Tubular Maximum for Phosphorous/Glomerular Filtration Rate (TMP/GFR)
Fractional tubular reabsorption of phosphate (TRP) = 1-{(U phos/P phos) x ( P creat/U creat)} if TRP < or = 0.86 then TMP/GFR = TRP x P phos if TRP > 0.86 then TMP/GFR = 0.3 x TRP/{1-(0.8 x TRP)} x P phos
U= urine, P = plasma
Measured: Baseline, Day 15, Day 30, Day 60, Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2009 (estimated)
- Study startMay 2009
- Primary completionFeb 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Mara Horwitz, University of Pittsburgh
- Investigators
- Mara J Horwitz, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00853723
- Sponsor's protocol ID
- PRO08100148
- Other IDs
- R01DK051081
- Status last verified
- Feb 2016
- First submitted
- 27 Feb 2009
- Last updated
- 24 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
http://www.nof.org/osteoporosis/diseasefacts.htm. Accessed August 22, 2008
Black DM, Bouxsein ML, Palermo L, McGowan JA, Newitt DC, Rosen E, Majumdar S, Rosen CJ; PTH Once-Weekly Research (POWR) Group. Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling. J Clin Endocrinol Metab. 2008 Jun;93(6):2166-72. doi: 10.1210/jc.2007-2781. Epub 2008 Mar 18.
PubMed 18349061Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. JAMA. 1996 Nov 6;276(17):1389-96.
PubMed 8892713Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med. 1995 Nov 30;333(22):1437-43. doi: 10.1056/NEJM199511303332201.
PubMed 7477143Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, Draper M, Christiansen C. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997 Dec 4;337(23):1641-7. doi: 10.1056/NEJM199712043372301.
PubMed 9385122Chesnut CH 3rd, Silverman S, Andriano K, Genant H, Gimona A, Harris S, Kiel D, LeBoff M, Maricic M, Miller P, Moniz C, Peacock M, Richardson P, Watts N, Baylink D. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med. 2000 Sep;109(4):267-76. doi: 10.1016/s0002-9343(00)00490-3.
PubMed 10996576Fogelman I, Ribot C, Smith R, Ethgen D, Sod E, Reginster JY. Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group. J Clin Endocrinol Metab. 2000 May;85(5):1895-900. doi: 10.1210/jcem.85.5.6603.
PubMed 10843171Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10;344(19):1434-41. doi: 10.1056/NEJM200105103441904.
PubMed 11346808Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE. Biochemical evaluation of patients with cancer-associated hypercalcemia: evidence for humoral and nonhumoral groups. N Engl J Med. 1980 Dec 11;303(24):1377-83. doi: 10.1056/NEJM198012113032401.
PubMed 6253785Stewart AF, Vignery A, Silverglate A, Ravin ND, LiVolsi V, Broadus AE, Baron R. Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity. J Clin Endocrinol Metab. 1982 Aug;55(2):219-27. doi: 10.1210/jcem-55-2-219.
PubMed 7085851Strewler GJ. The physiology of parathyroid hormone-related protein. N Engl J Med. 2000 Jan 20;342(3):177-85. doi: 10.1056/NEJM200001203420306. No abstract available.
PubMed 10639544Broadus AE, Mangin M, Ikeda K, Insogna KL, Weir EC, Burtis WJ, Stewart AF. Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide. N Engl J Med. 1988 Sep 1;319(9):556-63. doi: 10.1056/NEJM198809013190906. No abstract available.
PubMed 3043221Philbrick WM, Wysolmerski JJ, Galbraith S, Holt E, Orloff JJ, Yang KH, Vasavada RC, Weir EC, Broadus AE, Stewart AF. Defining the roles of parathyroid hormone-related protein in normal physiology. Physiol Rev. 1996 Jan;76(1):127-73. doi: 10.1152/physrev.1996.76.1.127.
PubMed 8592727Orloff JJ, Reddy D, de Papp AE, Yang KH, Soifer NE, Stewart AF. Parathyroid hormone-related protein as a prohormone: posttranslational processing and receptor interactions. Endocr Rev. 1994 Feb;15(1):40-60. doi: 10.1210/edrv-15-1-40.
PubMed 8156938Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocana A, Stewart AF. Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers. J Clin Endocrinol Metab. 2003 Apr;88(4):1603-9. doi: 10.1210/jc.2002-020773.
PubMed 12679445
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of 3 Month PTHrP(1-36) and PTH(1-34) on Post-Menopausal Osteoporosis
- ClinicalTrials.gov ID
- NCT00853723
- Acronym / sponsor ID
- PRO08100148
- Conditions
- Osteoporosis
- Keywords
- osteoporosis, post-menopausal, bone anabolic agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- May 2009
- Primary completion
- Feb 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 2 Mar 2009 (estimated)
- Results
- Posted 24 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a three month comparison trial of standard dose parathyroid hormone (PTH) (1-34) and two different doses of Parathyroid Hormone-related Protein (PTHrP) (1-36). The investigators want to to demonstrate that daily subcutaneous injection of PTHrP (1-36) in postmenopausal women with osteoporosis stimulates bone formation to the same or greater degree than PTH (1-34) but with less bone resorption.
Detailed description
Osteoporosis is a metabolic bone disease characterized by low bone mass and structural deterioration of bone tissue. It results from failure of osteoblasts to form sufficient new bone, from an excessive rate of osteoclastic bone resorption, or from the combination of both processes. The resultant bone fragility leads to an increased susceptibility to fractures, especially of the hip, spine and wrist. There is an increased mortality rate following both hip and vertebral fractures, and the presence of one fracture is a potent risk factor for future fractures. This leads to a decline in the quality of life and an associated loss of independence among the millions of individuals in the United States and worldwide afflicted with the disease. There is an additional population at an increased risk for fractures due to a less severe loss of bone mass, known as osteopenia (1). Already ten million individuals in the United States are estimated to have the disease and thirty four million more are at increased risk due to low bone mass (1).
Approved pharmacological treatments for postmenopausal osteoporosis include two classes of drugs: the antiresorptive and the anabolics (2). The antiresorptive include estrogen, calcitonin, selective estrogen receptor modulators, and bisphosphonates. The antiresorptive medications prevent bone loss by inhibiting both osteoclastic bone resorption and formation, by slowing bone turnover, and by allowing for increased mineralization of osteoid (2). The increase in bone mineral density from the antiresorptive agents is generally reported to be in the range of 2-8% over 1-7 years (3-7).
There is only one anabolic agent that is presently approved by the FDA for treatment for osteoporosis: parathyroid hormone, PTH (1-34), or teriparatide. PTH(1-34) was approved by the FDA in 2002 and it acts by increasing bone density by stimulating the PTH-1 receptor. This induces an increase in osteoblast mediated bone formation and osteoclast mediated bone resorption. Daily subcutaneous PTH is anabolic as there is stimulation of bone formation to a greater extent than bone resorption. The overall net result of biosynthetic PTH (1-34) is an increase in bone mineral density and a decrease in fractures (8). Daily PTH(1-34) treatment has been shown to effectively reduce the risk of both vertebral and nonvertebral fractures. Measurements of bone mineral density (BMD) of the lumbar spine (LS) resulted in an increase in bone density of 9 percent when compared to placebo (9). A daily 20 microgram dose of subcutaneous PTH(1-34) reduced the risk of getting two or more vertebral fractures by 77%, and the risk of at least one moderate or severe fracture was reduced by 90 and 78% respectively (9). Additionally, one vertebral fracture was prevented for every 12 patient years of treatment, and women were 35% less likely to have one or more new nonvertebral fragility fractures (9).
Parathyroid hormone-related protein or PTHrP is a protein peptide that was first isolated in 1987 as the factor responsible for the syndrome of humoral hypercalcemia of malignancy (HHM) (10-14). PTHrP is found in almost every tissue and cell type in the body, and appears to regulate cellular proliferation, survival, and differentiation in normal tissue as well as in malignancies (15-16). As the name implies, PTHrP is similar to PTH. Both peptides bind to the same receptor, PTH-1 R, and activate downstream signaling pathways causing similar post receptor effects (17).
Since PTH is a potent anabolic agent, we hypothesize that PTHrP may act in an anabolic fashion as well. We are seeking to demonstrate in this study that PTHrP acts as an anabolic agent in the treatment of osteoporosis with similar or better efficacy than PTH in respect to bone formation but with less bone resorption and fewer side effects, such as hypercalcemia.
The current studies are a sequel to initial phase 1 trials assessing the efficacy and safety of daily subcutaneous injection of PTHrP on the human skeleton. Previous studies have demonstrated that a single daily injection of ~ 400 mcg/day of PTHrP (1-36) in postmenopausal women on estrogen with osteoporosis led to a 4.7% increase in lumbar spine bone mineral density (BMD) after three months and all subjects were free of hypercalcemia or other adverse effects (18). In contrast with PTH, the doses of PTHrP are much larger, yet well-tolerated, and the increments in spine BMD are large and rapid with some subjects showing increases in spine BMD of 6-8% in as soon as three months in studies done thus far (18). PTHrP appears to selectively stimulate bone formation without stimulating bone resorption (18). This exciting observation may point towards PTHrP being a pure skeletal anabolic agent (21). Preliminary data analysis from a more recent three week dose escalation trial indicates demonstrates that the dose of 500 mcg/day of PTHrP causes 38% increase in P1NP and a 20% decrease in CTX indicating far greater bone formation than bone resorption with no hypercalcemia. At 625 mcg/day there were similar increases in P1NP with hypercalcemia in only 10% of subjects and hypercalcuria in 20%. In contrast in subjects receiving 750 mcg/day 50% developed hypercalcemia requiring early termination. The P1NP and CTX data from the three week dose escalation trial was used for both determining dose and sample size calculations for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PTHrP 400 mcg/day | Experimental | Drug: Parathyroid hormone related protein (1-36)Post-menopausal women with osteoporosis will subcutaneously administer PTHrP 400 micrograms daily for three months. |
| PTHrP 600 mcg/day | Experimental | Drug: Parathyroid hormone related protein(1-36)Post-menopausal women with osteoporosis will subcutaneously administer PTHrP 600 micrograms daily for three months. |
| PTH 20 mcg/day | Active comparator | Drug: Parathyroid hormone (1-34)Post-menopausal women with osteoporosis will subcutaneously administer the FDA approved dose of PTH 20 micrograms daily for three months. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 45 - 75 year old Caucasian, Hispanic or Asian women
- one year post-menopausal if older than 50 years
- three years post-menopausal if between the ages of 45 - 50 years
- body mass index less than or equal to 30
- T-scores on screening Dual X-Ray Absorbiometry (DXA) scan between - 2.0 to - 4.5 of lumbar spine or hip
Key exclusion criteria (12 listed)
- bisphosphonate therapy within the last two years
- estrogen replacement hormones or SERMS within last one year
- no more than one week of PTHrP, PTH, or an analog of PTH within the last year
- an atraumatic bone fracture within the last 6 months
- significant or active diseases of any organ system
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Parathyroid hormone related protein (1-36)Also: PTHrP (1-36), PTHrPPTHrP (1-36) 400 micrograms / day administered subcutaneously for 3 months | Drug | PTHrP 400 mcg/day |
| Parathyroid hormone related protein(1-36)Also: PTHrP (1-36), PTHrPPTHrP(1-36)600 micrograms subcutaneously administered daily for 3 months | Drug | PTHrP 600 mcg/day |
| Parathyroid hormone (1-34)Also: PTH(1-34), Teriparatide (brand name: Forteo)PTH(1-34)20 micrograms subcutaneously administered daily for 3 months | Drug | PTH 20 mcg/day |
Primary outcome
Procallagen-1 Amino-terminal Peptide (P1NP)
Time frame: Baseline, Day 15, Day 30, Day 60, Day 90
Carboxy-terminal Telopeptides of Collagen-1 (CTX)
Time frame: Baseline, Day 15, Day 30, Day 60, Day 90
11 secondary outcomes
Changes in Bone Mineral Density of the Lumbar Spine.
Time frame: 90 days
Changes in Bone Mineral Density of the Total Hip.
Time frame: 90 days
Changes in Bone Mineral Density of the Femoral Neck.
Time frame: 90 days
Changes in Bone Mineral Density of the Forearm.
Time frame: 90 days
Changes in Bone Mineral Density of the Distal 1/3 Radius.
Time frame: 90 days
Total Serum Calcium (mg/dl)
Time frame: Baseline, Day 15, Day 30, Day 60, Day 90
Serum Phosphorous
Time frame: Baseline, Day 15, Day 30, Day 60, Day 90
24 Hour Urine Calcium
Time frame: 90 days
1,25 Vitamin D
Time frame: Baseline, Day 15, Day 30, Day 60, Day 90
Fractional Excretion of Calcium
Time frame: Baseline, Day 15, Day 30, Day 60, Day 90
Tubular Maximum for Phosphorous/Glomerular Filtration Rate (TMP/GFR)
Time frame: Baseline, Day 15, Day 30, Day 60, Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Backgroundhttp://www.nof.org/osteoporosis/diseasefacts.htm. Accessed August 22, 2008
- Background: PubMed 18349061Black DM, Bouxsein ML, Palermo L, McGowan JA, Newitt DC, Rosen E, Majumdar S, Rosen CJ; PTH Once-Weekly Research (POWR) Group. Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling. J Clin Endocrinol Metab. 2008 Jun;93(6):2166-72. doi: 10.1210/jc.2007-2781. Epub 2008 Mar 18.
- Background: PubMed 8892713Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. JAMA. 1996 Nov 6;276(17):1389-96.
- Background: PubMed 7477143Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med. 1995 Nov 30;333(22):1437-43. doi: 10.1056/NEJM199511303332201.
- Background: PubMed 9385122Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, Draper M, Christiansen C. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997 Dec 4;337(23):1641-7. doi: 10.1056/NEJM199712043372301.
- Background: PubMed 10996576Chesnut CH 3rd, Silverman S, Andriano K, Genant H, Gimona A, Harris S, Kiel D, LeBoff M, Maricic M, Miller P, Moniz C, Peacock M, Richardson P, Watts N, Baylink D. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med. 2000 Sep;109(4):267-76. doi: 10.1016/s0002-9343(00)00490-3.
- Background: PubMed 10843171Fogelman I, Ribot C, Smith R, Ethgen D, Sod E, Reginster JY. Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group. J Clin Endocrinol Metab. 2000 May;85(5):1895-900. doi: 10.1210/jcem.85.5.6603.
- Background: PubMed 11346808Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10;344(19):1434-41. doi: 10.1056/NEJM200105103441904.
- Background: PubMed 6253785Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE. Biochemical evaluation of patients with cancer-associated hypercalcemia: evidence for humoral and nonhumoral groups. N Engl J Med. 1980 Dec 11;303(24):1377-83. doi: 10.1056/NEJM198012113032401.
- Background: PubMed 7085851Stewart AF, Vignery A, Silverglate A, Ravin ND, LiVolsi V, Broadus AE, Baron R. Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity. J Clin Endocrinol Metab. 1982 Aug;55(2):219-27. doi: 10.1210/jcem-55-2-219.
- Background: PubMed 10639544Strewler GJ. The physiology of parathyroid hormone-related protein. N Engl J Med. 2000 Jan 20;342(3):177-85. doi: 10.1056/NEJM200001203420306. No abstract available.
- Background: PubMed 3043221Broadus AE, Mangin M, Ikeda K, Insogna KL, Weir EC, Burtis WJ, Stewart AF. Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide. N Engl J Med. 1988 Sep 1;319(9):556-63. doi: 10.1056/NEJM198809013190906. No abstract available.
- Individual participant dataSharing planned: No
Related trials for Osteoporosis
RecruitingObservational study
A Clinical Study to Collect Real-wordt Data on Safety and Clinical Performance of the VCFix Spinal System for Treatment of Vertebral Compression Fractures of (Suspected) Osteoporotic Origin.
Vertebra Compression Fracture
Active, not recruitingObservational study
The Impact of Osteosarcopenia on Falls, Kinesiophobia, and Quality of Life in Postmenopausal Women
Osteosarcopenia, Sarcopenia
Active, not recruitingPhase 2
TCM Formula vs. HMB in Pre-Frail Elders: Muscle Strength and Bone Status
Pre-Frailty, Sarcopenia
Not yet recruitingPhase 4
Romosozumab and Denosumab Combination Therapy for Osteoporosis
Postmenopausal Osteoporosis
RecruitingObservational study
Assessment and Comparison of Osteoporosis Risk Factors After Stroke
Stroke, Osteoporosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mara J Horwitz, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Parathyroid hormone related protein (1-36), Parathyroid hormone related protein(1-36) and Parathyroid hormone (1-34) in people with Osteoporosis, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Procallagen-1 Amino-terminal Peptide (P1NP) (time frame: Baseline, Day 15, Day 30, Day 60, Day 90). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00853723, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2016.