NCT00853723

Brief 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 formation to the same or greater degree than PTH (1-34) but with less bone resorption.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
105

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started May 2009

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 27, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 2, 2009

Completed
2 months until next milestone

Study Start

First participant enrolled

May 1, 2009

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2012

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed
3.7 years until next milestone

Results Posted

Study results publicly available

February 24, 2016

Completed
Last Updated

March 24, 2016

Status Verified

February 1, 2016

Enrollment Period

2.8 years

First QC Date

February 27, 2009

Results QC Date

July 15, 2015

Last Update Submit

February 24, 2016

Conditions

Osteoporosis

Keywords

osteoporosispost-menopausalbone anabolic agents

Outcome Measures

Primary Outcomes (2)

  • Procallagen-1 Amino-terminal Peptide (P1NP)

    Baseline, Day 15, Day 30, Day 60, Day 90

  • Carboxy-terminal Telopeptides of Collagen-1 (CTX)

    Baseline, Day 15, Day 30, Day 60, Day 90

Secondary Outcomes (11)

  • Changes in Bone Mineral Density of the Lumbar Spine.

    90 days

  • Changes in Bone Mineral Density of the Total Hip.

    90 days

  • Changes in Bone Mineral Density of the Femoral Neck.

    90 days

  • Changes in Bone Mineral Density of the Forearm.

    90 days

  • Changes in Bone Mineral Density of the Distal 1/3 Radius.

    90 days

  • +6 more secondary outcomes

Study Arms (3)

PTHrP 400 mcg/day

EXPERIMENTAL

Post-menopausal women with osteoporosis will subcutaneously administer PTHrP 400 micrograms daily for three months.

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.

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.

Drug: Parathyroid hormone (1-34)

Interventions

Parathyroid hormone related protein (1-36)DRUG

PTHrP (1-36) 400 micrograms / day administered subcutaneously for 3 months

Also known as: PTHrP (1-36), PTHrP
PTHrP 400 mcg/day
Parathyroid hormone related protein(1-36)DRUG

PTHrP(1-36)600 micrograms subcutaneously administered daily for 3 months

Also known as: PTHrP (1-36), PTHrP
PTHrP 600 mcg/day
Parathyroid hormone (1-34)DRUG

PTH(1-34)20 micrograms subcutaneously administered daily for 3 months

Also known as: PTH(1-34), Teriparatide (brand name: Forteo)
PTH 20 mcg/day

Eligibility Criteria

Age45 Years - 75 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UPMC Clinical & Translational Research Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (27)

  • http://www.nof.org/osteoporosis/diseasefacts.htm. Accessed August 22, 2008

    BACKGROUND

  • 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.

    PMID: 18349061BACKGROUND

  • 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.

    PMID: 8892713BACKGROUND

  • Liberman 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.

    PMID: 7477143BACKGROUND

  • 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. doi: 10.1056/NEJM199712043372301.

    PMID: 9385122BACKGROUND

  • 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. doi: 10.1016/s0002-9343(00)00490-3.

    PMID: 10996576BACKGROUND

  • 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. doi: 10.1210/jcem.85.5.6603.

    PMID: 10843171BACKGROUND

  • 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. doi: 10.1056/NEJM200105103441904.

    PMID: 11346808BACKGROUND

  • 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. doi: 10.1056/NEJM198012113032401.

    PMID: 6253785BACKGROUND

  • 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. doi: 10.1210/jcem-55-2-219.

    PMID: 7085851BACKGROUND

  • Strewler 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.

    PMID: 10639544BACKGROUND

  • 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. doi: 10.1056/NEJM198809013190906. No abstract available.

    PMID: 3043221BACKGROUND

  • 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. doi: 10.1152/physrev.1996.76.1.127.

    PMID: 8592727BACKGROUND

  • 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. doi: 10.1210/edrv-15-1-40.

    PMID: 8156938BACKGROUND

  • 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. doi: 10.1210/jc.2002-020773.

    PMID: 12679445BACKGROUND

  • 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. doi: 10.1210/jc.2002-021122.

    PMID: 12574182BACKGROUND

  • 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. doi: 10.1359/jbmr.2000.15.8.1517.

    PMID: 10934650BACKGROUND

  • 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. doi: 10.1210/me.2007-0274. Epub 2007 Sep 13.

    PMID: 17872377BACKGROUND

  • 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. doi: 10.1210/en.2004-0509. No abstract available.

    PMID: 15265822BACKGROUND

  • 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. 2006 Feb;17(2):225-30. doi: 10.1007/s00198-005-1976-3. Epub 2005 Sep 7.

    PMID: 16151606BACKGROUND

  • FORTEO (package insert). Indianapolis, IN: Eli Lilly and Company; 2008.

    BACKGROUND

  • 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. doi: 10.1210/jc.2006-2439. Epub 2007 Jul 3.

    PMID: 17609307BACKGROUND

  • 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. doi: 10.1001/archinte.165.15.1762.

    PMID: 16087825BACKGROUND

  • 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. doi: 10.1111/j.1742-1241.2008.01768.x. Epub 2008 Apr 17.

    PMID: 18422590BACKGROUND

  • 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. doi: 10.1359/JBMR.051023. Epub 2005 Nov 11. No abstract available.

    PMID: 16491282BACKGROUND

  • 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.

    BACKGROUND

  • Lachin JM. Introduction to sample size determination and power analysis for clinical trials. Control Clin Trials. 1981 Jun;2(2):93-113. doi: 10.1016/0197-2456(81)90001-5.

    PMID: 7273794BACKGROUND

MeSH Terms

Conditions

Osteoporosis

Interventions

parathyroid hormone-related peptide (1-36)Parathyroid Hormone-Related ProteinParathyroid HormoneTeriparatide

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Peptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Limitations and Caveats

This study was not double-blinded. There was no placebo group in this study. Subjects had higher than anticipated calcium intake and baseline vitamin D levels.

Results Point of Contact

Title
Mara J Horwitz
Organization
UPittsburgh
horwitz@pitt.edu
4126922848

Study Officials

  • Mara J Horwitz, MD

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor, University of Pittsburgh School of Medicine

Study Record Dates

First Submitted

February 27, 2009

First Posted

March 2, 2009

Study Start

May 1, 2009

Primary Completion

February 1, 2012

Study Completion

June 1, 2012

Last Updated

March 24, 2016

Results First Posted

February 24, 2016

Record last verified: 2016-02

Data Sharing

IPD Sharing
Will not share

Locations

US(1)