NCT00177411

Brief Summary

This is a single-blinded, one-treatment, combination dose escalation and pharmacokinetic study done in healthy volunteers. The investigators want to determine whether Parathyroid Hormone related Protein (1-36) \[PTHrP(1-36)\] shares anabolic properties with the only currently approved anabolic agent, parathyroid hormone(1-34) \[PTH(1-34)\], which stimulates both osteoblastic bone resorption and formation. In a previous study done by the investigators, postmenopausal osteoporotic women on estrogen received 6.56 mcg/kg PTHrP(1-36) subcutaneously for three months daily. They experiences a 4.7% increase in bone mineral density (BMD) of the lumbar spine when compared with those taking placebo. They also displayed an increase in serum osteocalcin, a marker of bone formation, with no change in several markers of bone resorption. It is believed that the rapid absorption and clearance of PTHrP(1-36) likely plays a central role in its anabolic effect In order to further assess absorption, we are combining both pharmacokinetic and dose escalation methods for studying intravenous PTHrP given via a one-time bolus injection. The purpose is to define the maximum safe dose and measure the pharmacokinetic parameters of a single intravenous dose of Parathyroid Hormone-related Protein (1-36)\[PTHrP(1-36)\]. The results will be useful in determining future treatment options for osteoporosis.

Trial Health

30
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Timeline
Completed

Started Jul 2005

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
withdrawn

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

Study Start

First participant enrolled

July 1, 2005

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 12, 2005

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 15, 2005

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2007

Completed
Last Updated

September 5, 2014

Status Verified

September 1, 2014

Enrollment Period

2 years

First QC Date

September 12, 2005

Last Update Submit

September 3, 2014

Conditions

Osteoporosis

Keywords

Endocrine System DiseasesMusculoSkeletal System DiseasesHormonePostmenopausal Women

Outcome Measures

Primary Outcomes (1)

  • The absence of any dose limiting toxicity criteria

    6 hours

Secondary Outcomes (1)

  • Measurement of vitamin D levels, markers of bone metabolism and fractional excretion of calcium measurements

    6 hours

Study Arms (1)

PTHrP group

EXPERIMENTAL

Subjects receiving PTHrP in varying doses.

Drug: Parathyroid Hormone-related Protein

Interventions

Parathyroid Hormone-related ProteinDRUG

Parathyroid Hormone-related Protein in doses started at a 4 microgram single bolus intravenous dose. Dose will be increase to a maximum of 400 micrograms or until a dose limiting toxicity occurs at a lower dose.

Also known as: PTHrP(1-36)
PTHrP group

Eligibility Criteria

Age24 Years - 35 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy Caucasian subjects of both sexes between the ages of 24-35 years -

You may not qualify if:

  • Pregnancy Subjects with cardiac, hypertension, vascular, renal, pulmonary, endocrine, musculoskeletal, hepatic hematologic or malignant or rheumatologic disease.
  • Body Mass Index greater than 30 anemia (hematocrit less than 36% in women, less than 40% in men) significant alcohol or drug abuse, baseline hypotension (systolic blood pressure less than 90 mm/HG) baseline hypertension (systolic BP greater than 140 mmHg or diastolic BP greater than 90 mmHg Abnormal screening labs including: ionized and total serum calcium, phosphorus, creatinine, albumin, 25-hydroxyvitamin D, and PTH.
  • Subjects taking any chronic medication except oral contraceptives Those who have received an investigational drug in the past 90 days Any subject who has previously received either PTH or PTHrP African Americans and other ethnic minorities will be excluded since it is well documented that osteoporosis is far more common in Caucasians than in African-Americans, and there are clear quantitative differences in bone density and sensitivity to parathyroid hormone between African-Americans and Caucasians. -

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (10)

  • 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

  • Syed MA, Horwitz MJ, Tedesco MB, Garcia-Ocana A, Wisniewski SR, Stewart AF. Parathyroid hormone-related protein-(1--36) stimulates renal tubular calcium reabsorption in normal human volunteers: implications for the pathogenesis of humoral hypercalcemia of malignancy. J Clin Endocrinol Metab. 2001 Apr;86(4):1525-31. doi: 10.1210/jcem.86.4.7406.

    PMID: 11297578BACKGROUND

  • 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

  • Everhart-Caye M, Inzucchi SE, Guinness-Henry J, Mitnick MA, Stewart AF. Parathyroid hormone (PTH)-related protein(1-36) is equipotent to PTH(1-34) in humans. J Clin Endocrinol Metab. 1996 Jan;81(1):199-208. doi: 10.1210/jcem.81.1.8550752.

    PMID: 8550752BACKGROUND

  • Henry JG, Mitnick M, Dann PR, Stewart AF. Parathyroid hormone-related protein-(1-36) is biologically active when administered subcutaneously to humans. J Clin Endocrinol Metab. 1997 Mar;82(3):900-6. doi: 10.1210/jcem.82.3.3811.

    PMID: 9062504BACKGROUND

  • Plotkin H, Gundberg C, Mitnick M, Stewart AF. Dissociation of bone formation from resorption during 2-week treatment with human parathyroid hormone-related peptide-(1-36) in humans: potential as an anabolic therapy for osteoporosis. J Clin Endocrinol Metab. 1998 Aug;83(8):2786-91. doi: 10.1210/jcem.83.8.5047.

    PMID: 9709948BACKGROUND

  • 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

  • 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, Syed MA, Garcia-Ocana A, Bisello A, Hollis BW, Rosen CJ, Wysolmerski JJ, Dann P, Gundberg C, Stewart AF. Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D. J Bone Miner Res. 2005 Oct;20(10):1792-803. doi: 10.1359/JBMR.050602. Epub 2005 Jun 6.

    PMID: 16160737BACKGROUND

  • 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

MeSH Terms

Conditions

OsteoporosisEndocrine System DiseasesMusculoskeletal Diseases

Interventions

Parathyroid Hormone-Related Proteinparathyroid hormone-related peptide (1-36)

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Mara J. Horwitz, MD

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Medicne

Study Record Dates

First Submitted

September 12, 2005

First Posted

September 15, 2005

Study Start

July 1, 2005

Primary Completion

July 1, 2007

Study Completion

July 1, 2007

Last Updated

September 5, 2014

Record last verified: 2014-09

Locations

US(1)