Comparison Study of PTHrP and PTH to Treat Osteoporosis - Full Text View

Purpose

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). 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.

Condition	Intervention	Phase
Osteoporosis	Drug: Parathyroid hormone related protein (1-36) Drug: Parathyroid hormone related protein(1-36) Drug: Parathyroid hormone (1-34)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Comparison of 3 Month PTHrP(1-36) and PTH(1-34) on Post-Menopausal Osteoporosis

Resource links provided by NLM:

MedlinePlus related topics: Menopause Osteoporosis

Drug Information available for: Parathyroid Hormone Teriparatide Teriparatide acetate

U.S. FDA Resources

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

Comparison of PTHrP groups with PTH group on procollagen-1 amino-terminal peptide (P1NP)and plasma carboxy-terminal peptide of procollagen-1 (CTX)measurements after 3 months of treatment relative to baseline. [ Time Frame: At study completion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in bone mineral density of the lumbar spine, hip, and wrist in subjects receiving both PTH and PTHrP. [ Time Frame: At study completion ] [ Designated as safety issue: No ]
Demonstration of safety parameters of three months of PTHrP treatment. [ Time Frame: At study completion ] [ Designated as safety issue: Yes ]
Evaluation of changes in other markers of bone metabolism in subjects receiving both PTH and PTHrP. [ Time Frame: At study completion ] [ Designated as safety issue: No ]

Enrollment:	377
Study Start Date:	May 2009
Study Completion Date:	June 2012
Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PTHrP 400 mcg/day Post-menopausal women with osteoporosis will subcutaneously administer PTHrP 400 micrograms daily for three months.	Drug: Parathyroid hormone related protein (1-36) PTHrP (1-36) 400 micrograms / day administered subcutaneously for 3 months Other Names: PTHrP (1-36) PTHrP
Experimental: PTHrP 600 mcg/day Post-menopausal women with osteoporosis will subcutaneously administer PTHrP 600 micrograms daily for three months.	Drug: Parathyroid hormone related protein(1-36) PTHrP(1-36)600 micrograms subcutaneously administered daily for 3 months Other Names: PTHrP (1-36) PTHrP
Active Comparator: PTH 20 mcg/day Post-menopausal women with osteoporosis will subcutaneously administer the FDA approved dose of PTH 20 micrograms daily for three months.	Drug: Parathyroid hormone (1-34) PTH(1-34)20 micrograms subcutaneously administered daily for 3 months Other Names: Parathyroid hormone (1-34) PTH(1-34) Teriparatide (brand name: Forteo)

Show Detailed Description

Eligibility

Ages Eligible for Study:	45 Years to 75 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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 DXA scan between - 2.0 to - 4.5 of lumbar spine or hip
have at lease two spinal vertebrae evaluable by DXA analysis

Exclusion Criteria:

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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853723

Locations

United States, Pennsylvania
UPMC Clinical & Translational Research Center
Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

University of Pittsburgh

National Institutes of Health (NIH)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator:

Mara J Horwitz, MD

University of Pittsburgh

More Information

Publications:

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. Epub 2008 Mar 18.

[No authors listed] Effects 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.

Liberman UA, Weiss SR, Bröll 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.

Delmas 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.

Chesnut 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.

Fogelman 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.

Neer 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.

Stewart 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.

Stewart 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.

Strewler GJ. The physiology of parathyroid hormone-related protein. N Engl J Med. 2000 Jan 20;342(3):177-85. Review. No abstract available.

Broadus 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. Review. No abstract available.

Philbrick 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. Review.

Orloff 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. Review.

Horwitz 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.

Horwitz MJ, Tedesco MB, Gundberg C, Garcia-Ocana A, Stewart AF. Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2003 Feb;88(2):569-75.

Stewart AF, Cain RL, Burr DB, Jacob D, Turner CH, Hock JM. Six-month daily administration of parathyroid hormone and parathyroid hormone-related protein peptides to adult ovariectomized rats markedly enhances bone mass and biomechanical properties: a comparison of human parathyroid hormone 1-34, parathyroid hormone-related protein 1-36, and SDZ-parathyroid hormone 893. J Bone Miner Res. 2000 Aug;15(8):1517-25.

Dean T, Vilardaga JP, Potts JT Jr, Gardella TJ. Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. Mol Endocrinol. 2008 Jan;22(1):156-66. Epub 2007 Sep 13.

Bisello A, Horwitz MJ, Stewart AF. Parathyroid hormone-related protein: an essential physiological regulator of adult bone mass. Endocrinology. 2004 Aug;145(8):3551-3. No abstract available.

Horwitz MJ, Tedesco MB, Sereika SM, Garcia-Ocana A, Bisello A, Hollis BW, Gundberg C, Stewart AF. Safety and tolerability of subcutaneous PTHrP(1-36) in healthy human volunteers: a dose escalation study. Osteoporos Int. 2005 Sep 7; [Epub ahead of print]

Miller PD, Bilezikian JP, Diaz-Curiel M, Chen P, Marin F, Krege JH, Wong M, Marcus R. Occurrence of hypercalciuria in patients with osteoporosis treated with teriparatide. J Clin Endocrinol Metab. 2007 Sep;92(9):3535-41. Epub 2007 Jul 3.

McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med. 2005 Aug 8-22;165(15):1762-8. Erratum in: Arch Intern Med. 2005 Oct 10;165(18):2120.

Anastasilakis AD, Goulis DG, Polyzos SA, Gerou S, Koukoulis GN, Efstathiadou Z, Kita M, Avramidis A. Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trial. Int J Clin Pract. 2008 Jun;62(6):919-24. Epub 2008 Apr 17.

Tashjian AH Jr, Gagel RF. Teriparatide [human PTH(1-34)]: 2.5 years of experience on the use and safety of the drug for the treatment of osteoporosis. J Bone Miner Res. 2006 Mar;21(3):354-65. Epub 2005 Nov 11. Review. No abstract available.

Horwitz MJ, Stewart Af. Humoral hypercalcemia of malignancy. In: Favus MF (ed.) Primer on Metabolic Bone Diseases and Disorders of Mineral Metabolism, 5th ed. American Society for Bone and Mineral Research, Washington, DC, USA, pp. 246-250:2003.

Lachin JM. Introduction to sample size determination and power analysis for clinical trials. Control Clin Trials. 1981 Jun;2(2):93-113.

Responsible Party:	Mara Horwitz, Associate Professor, University of Pittsburgh School of Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00853723 History of Changes
Other Study ID Numbers:	PRO08100148, R01DK051081
Study First Received:	February 27, 2009
Last Updated:	June 20, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:

osteoporosis
post-menopausal
bone anabolic agents

Additional relevant MeSH terms:

Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013