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One Week Comparison Study of PTH and PTHrP Infusions

This study has been withdrawn prior to enrollment.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01333267
First Posted: April 11, 2011
Last Update Posted: December 5, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Mara Horwitz, University of Pittsburgh
  Purpose
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium. These results will be compared to previous studies of Caucasian volunteers.

Condition Intervention Phase
Osteoporosis Hypercalcemia of Malignancy Hyperparathyroidism Bone Diseases, Endocrine Drug: Parathyroid Hormone-related Protein (1-36) Drug: parathyroid hormone (1-34) Drug: PTH (1-34) and PTHrP (1-36) Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Official Title: Comparison of Skeletal and Mineral Metabolism Responses in Healthy African-Americans and Caucasians Using a Continuous Seven-Day Parathyroid Hormone (PTH) or Parathyroid Hormone-related Protein (PTHrP) Infusion

Resource links provided by NLM:


Further study details as provided by Mara Horwitz, University of Pittsburgh:

Primary Outcome Measures:
  • Safety: The absence of any dose limiting toxicity (DLT) criteria consisting of one major criteria or two minor criteria. [ Time Frame: one week ]

Secondary Outcome Measures:
  • Blood collections analyzed for measurements of PTH(1-34), PTH(1-84), 25-OH vitamin D, 1,25(OH)2 vitamin D, markers of bone metabolism, and fractional excretion of calcium measurements. [ Time Frame: one week ]

Enrollment: 0
Study Start Date: January 2015
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PTHrP group
Subjects receive PTHrP(1-36) starting with doses of 2 picomoles (pmols)/kg/hr for one week. Subsequent dosing groups are determined by the response to PTHrP doses.
Drug: Parathyroid Hormone-related Protein (1-36)
PTHrP (1-36) intravenously at 2 picomoles (pmols)/kg/hr for one week; doses will be increased by 2 picomoles (pmols)/kg/hr in subsequent subjects.
Other Names:
  • PTHrP(1-36)
  • Bone anabolic agents
Drug: PTH (1-34) and PTHrP (1-36)
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium.
Other Names:
  • Parathyroid Hormone-related Protein (1-36)
  • PTHrP(1-36)
  • IND 49,175
  • Parathyroid Hormone (1-34)
  • PTH (1-34)
  • IND 60,979
Experimental: PTH dosing group
Subjects receive PTH(1-34) starting with doses of 2 picomoles (pmols)/kg/hr for one week. Subsequent dosing groups are determined by the response to PTH doses.
Drug: parathyroid hormone (1-34)
PTH (1-34) intravenously at 2 picomoles (pmols)/kg/hr for one week; doses will be increased by 2 picomoles (pmols)/kg/hr in subsequent subjects.
Other Names:
  • PTH(1-34)
  • Bone anabolic agent
Drug: PTH (1-34) and PTHrP (1-36)
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium.
Other Names:
  • Parathyroid Hormone-related Protein (1-36)
  • PTHrP(1-36)
  • IND 49,175
  • Parathyroid Hormone (1-34)
  • PTH (1-34)
  • IND 60,979

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   24 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy African-American subjects of both sexes between the ages of 24-35 years, who are able to spend one week on the Clinical & Translational Research Center (CTRC) at the University of Pittsburgh Medical Center (UPMC) Montefiore.

Exclusion Criteria:

  • Subjects with cardiac, vascular, renal (serum creatinine > 1.5), pulmonary, endocrine, musculoskeletal, hepatic, hematologic, malignant, or rheumatologic disease will be excluded.
  • Those found to have vitamin D deficiency, defined as a 25-OH vitamin D level < 10 ng/mL will also be excluded.
  • Additionally, those with BMI > 30, anemia (hematocrit < 36% in women, <40% in men), significant alcohol use, illicit drug use, hypertension (BP>160/90), or baseline hypotension (systolic blood pressure < 90mmHg) will be excluded.
  • Those taking chronic medications (except oral contraceptive pills (OCP's) or stable doses of thyroid replacement) or those who have received an investigational drug in the past 90 days will also be excluded.
  • Prior participants in PTH or PTHrP studies will not be eligible to participate.
  • Additionally pregnant women and lactating women will be excluded; all women will have a urine pregnancy test performed immediately before starting the study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01333267


Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Mara J. Horwitz, MD University of Pittsburgh
  More Information

Publications:
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.
Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia-Ocaña 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. Epub 2005 Jun 6.
Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocaña 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.
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Luckey MM, Wallenstein S, Lapinski R, Meier DE. A prospective study of bone loss in African-American and white women--a clinical research center study. J Clin Endocrinol Metab. 1996 Aug;81(8):2948-56.
Thomas PA. Racial and ethnic differences in osteoporosis. J Am Acad Orthop Surg. 2007;15 Suppl 1:S26-30.
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Cauley JA, Lui LY, Ensrud KE, Zmuda JM, Stone KL, Hochberg MC, Cummings SR. Bone mineral density and the risk of incident nonspinal fractures in black and white women. JAMA. 2005 May 4;293(17):2102-8.
Opotowsky AR, Bilezikian JP. Racial differences in the effect of early milk consumption on peak and postmenopausal bone mineral density. J Bone Miner Res. 2003 Nov;18(11):1978-88.
Cosman F, Nieves J, Dempster D, Lindsay R. Vitamin D economy in blacks. J Bone Miner Res. 2007 Dec;22 Suppl 2:V34-8. doi: 10.1359/jbmr.07s220. Review.
Harris SS, Soteriades E, Dawson-Hughes B; Framingham Heart Study; Boston Low-Income Elderly Osteoporosis Study. Secondary hyperparathyroidism and bone turnover in elderly blacks and whites. J Clin Endocrinol Metab. 2001 Aug;86(8):3801-4.
Cosman F, Morgan DC, Nieves JW, Shen V, Luckey MM, Dempster DW, Lindsay R, Parisien M. Resistance to bone resorbing effects of PTH in black women. J Bone Miner Res. 1997 Jun;12(6):958-66.
Fuleihan GE, Gundberg CM, Gleason R, Brown EM, Stromski ME, Grant FD, Conlin PR. Racial differences in parathyroid hormone dynamics. J Clin Endocrinol Metab. 1994 Dec;79(6):1642-7.
Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr. 2008 Jun;87(6):1952-8.
Aloia JF. African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox. Am J Clin Nutr. 2008 Aug;88(2):545S-550S. Review.
Aloia JF, Talwar SA, Pollack S, Feuerman M, Yeh JK. Optimal vitamin D status and serum parathyroid hormone concentrations in African American women. Am J Clin Nutr. 2006 Sep;84(3):602-9.
Aloia JF, Talwar SA, Pollack S, Yeh J. A randomized controlled trial of vitamin D3 supplementation in African American women. Arch Intern Med. 2005 Jul 25;165(14):1618-23.
Barrett-Connor E, Siris ES, Wehren LE, Miller PD, Abbott TA, Berger ML, Santora AC, Sherwood LM. Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res. 2005 Feb;20(2):185-94. Epub 2004 Oct 18.
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Finkelstein JS, Lee ML, Sowers M, Ettinger B, Neer RM, Kelsey JL, Cauley JA, Huang MH, Greendale GA. Ethnic variation in bone density in premenopausal and early perimenopausal women: effects of anthropometric and lifestyle factors. J Clin Endocrinol Metab. 2002 Jul;87(7):3057-67.
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Cummings SR, Cauley JA, Palermo L, Ross PD, Wasnich RD, Black D, Faulkner KG. Racial differences in hip axis lengths might explain racial differences in rates of hip fracture. Study of Osteoporotic Fractures Research Group. Osteoporos Int. 1994 Jul;4(4):226-9.
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Responsible Party: Mara Horwitz, Associate Professor, University of Pittsburgh School of Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01333267     History of Changes
Other Study ID Numbers: PRO10060214
First Submitted: April 8, 2011
First Posted: April 11, 2011
Last Update Posted: December 5, 2014
Last Verified: December 2014

Keywords provided by Mara Horwitz, University of Pittsburgh:
Endocrine System Diseases
MusculoSkeletal System Disease
Hormones
Postmenopausal Women
Bone metabolism
Physiologic Properties
African-Americans

Additional relevant MeSH terms:
Osteoporosis
Hyperparathyroidism
Bone Diseases
Hypercalcemia
Paraneoplastic Syndromes
Endocrine System Diseases
Bone Diseases, Endocrine
Bone Diseases, Metabolic
Musculoskeletal Diseases
Parathyroid Diseases
Calcium Metabolism Disorders
Metabolic Diseases
Water-Electrolyte Imbalance
Neoplasms
Hormones
Anabolic Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs


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