3-Week Parathyroid Hormone-related Protein (PTHrP) Dose Escalation Study in Post-Menopausal Women

NCT00222872 | Completed Phase 1 DMC

• 2 other identifiers: IRB # 0503166NIH RO - DK 51081
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to determine the safety and effectiveness of three week daily subcutaneous injections of Parathyroid Hormone-related Protein (1-36). Previous studies indicated that PTHrP has a skeletal 'anabolic' or bone-building effect, and has shown to increase bone mineral density in postmenopausal women with osteoporosis. Safety of PTHrP will be determined by measurements of blood pressure and pulse, serum blood calcium levels and subjective symptoms. Effectiveness will be measured by changes in measurements of blood and urine markers of bone turnover.

Conditions

Osteoporosis; Osteoporosis, Postmenopausal

Keywords

Endocrine System Diseases; MusculoSkeletal System Diseases; Hormone; Postmenopausal Women

Outcome Measures

Primary Outcomes (1)

• Subjects will receive PTHrP without Dose Limiting Toxicity Events as established by safety parameters consisting of one major criteria or two minor criteria.

  3 weeks

Secondary Outcomes (1)

• 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.

  3 week

Study Arms (2)

1 - PTHrP Group

ACTIVE COMPARATOR

Group receiving study drug: PTHrP(1-36)

Drug: Parathyroid Hormone-related Protein

2 - Single Blind Placebo Group

PLACEBO COMPARATOR

Receives placebo injections daily via subcutaneous injection

Drug: Placebo

Interventions

Parathyroid Hormone-related Protein DRUG

PTHrP(1-36) starting at 500 micrograms, then increasing by 125 micrograms up to a maximum of 1,500 micrograms.

Also known as: study drug

1 - PTHrP Group

Placebo DRUG

Placebo drug via subcutaneous injection in single blinded fashion daily for 3 weeks

Also known as: Placebo group

2 - Single Blind Placebo Group

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women
• Caucasian
• Hispanic
• Asian
• One year past onset of menopause
• Weigh between 50 and 90 kilograms

You may not qualify if:

• Taking bisphosphonates in the last 2 years
• Estrogen replacement hormones in last year
• SERMS in last year
• One weeks worth of PTHrP, PTH or an analog of PTH in past year
• Recent non-traumatic bone fracture within last year
• Significant uncontrolled cardiac, vascular, renal, pulmonary, endocrine or rheumatologic disease
• History of malignancy
• Anemia
• Significant alcohol or drug abuse
• Receiving any investigational drug within past 90 days
• Medications that interfere with metabolism or renal clearance of study drug, oral or systemic glucocorticoids of \> 5 mg/day prednisone (or equivalent) over the past year
• Thiazide-type diuretics
• Abnormal screening labs (calcium, vit D and PTH, CBC)

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institutes of Health (NIH): collaborator
• Department of Health and Human Services: collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (9)

• 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: 11297578 BACKGROUND

• 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: 12574182 BACKGROUND

• 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: 12679445 BACKGROUND

• 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: 8550752 BACKGROUND

• 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: 9062504 BACKGROUND

• 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: 9709948 BACKGROUND

• 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: 15265822 BACKGROUND

• 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: 16160737 BACKGROUND

• 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: 16151606 BACKGROUND

MeSH Terms

Conditions

Osteoporosis; Osteoporosis, Postmenopausal; Endocrine System Diseases; Musculoskeletal Diseases

Interventions

Parathyroid Hormone-Related Protein; Drug Evaluation

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

• Mara J. Horwitz, M.D.

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 22, 2005
• Study Start: July 1, 2005
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: April 28, 2014

Record last verified: 2014-04

Locations

US (1)