One Week Comparison Study of PTH and PTHrP Infusions

This study is not yet open for participant recruitment.

Verified July 2012 by University of Pittsburgh

Sponsor:

Information provided by (Responsible Party):

Mara Horwitz, University of Pittsburgh

ClinicalTrials.gov Identifier:

NCT01333267

First received: April 8, 2011

Last updated: July 6, 2012

Last verified: July 2012

History of Changes

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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject)
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:

MedlinePlus related topics: Anabolic Steroids Bone Diseases Calcium Cancer Endocrine Diseases Osteoporosis Vitamin D

Drug Information available for: Parathyroid Hormone

U.S. FDA Resources

Further study details as provided by 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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	January 2013
Estimated Study Completion Date:	July 2014
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PTHrP group Subjects receive PTHrP(1-36) starting with doses of 2 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 pmols/kg/hr for one week; doses will be increased by 2 pmols/kg/hr in subsequent subjects. Other Names: Parathyroid Hormone-related Protein (1-36) 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 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 pmols/kg/hr for one week; doses will be increased by 2 pmols/kg/hr in subsequent subjects. Other Names: Parathyroid Hormone (1-34) 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

Arms

Assigned Interventions

Experimental: PTHrP group

Subjects receive PTHrP(1-36) starting with doses of 2 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 pmols/kg/hr for one week; doses will be increased by 2 pmols/kg/hr in subsequent subjects.

Other Names:

Parathyroid Hormone-related Protein (1-36)
PTHrP(1-36)
Bone anabolic agents

Drug: PTH (1-34) and PTHrP (1-36)

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 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 pmols/kg/hr for one week; doses will be increased by 2 pmols/kg/hr in subsequent subjects.

Other Names:

Parathyroid Hormone (1-34)
PTH(1-34)
Bone anabolic agent

Drug: PTH (1-34) and PTHrP (1-36)

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

Ages Eligible for Study:	24 Years to 35 Years
Genders Eligible for Study:	Both
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 at 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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01333267

Contacts

Contact: Mary Beth Tedesco, MNEd, CRNP	412-864-3265	tedesco@pitt.edu
Contact: Mara J Horwitz, MD	412-692-2848	horwitz@pitt.edu

Locations

United States, Pennsylvania
University of Pittsburgh Medical Center	Not yet recruiting
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-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. Epub 2005 Jun 6.

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.

Nelson DA, Jacobsen G, Barondess DA, Parfitt AM. Ethnic differences in regional bone density, hip axis length, and lifestyle variables among healthy black and white men. J Bone Miner Res. 1995 May;10(5):782-7.

George A, Tracy JK, Meyer WA, Flores RH, Wilson PD, Hochberg MC. Racial differences in bone mineral density in older men. J Bone Miner Res. 2003 Dec;18(12):2238-44.

Kalkwarf HJ, Zemel BS, Gilsanz V, Lappe JM, Horlick M, Oberfield S, Mahboubi S, Fan B, Frederick MM, Winer K, Shepherd JA. The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J Clin Endocrinol Metab. 2007 Jun;92(6):2087-99. Epub 2007 Feb 20.

Hui SL, Dimeglio LA, Longcope C, Peacock M, McClintock R, Perkins AJ, Johnston CC Jr. Difference in bone mass between black and white American children: attributable to body build, sex hormone levels, or bone turnover? J Clin Endocrinol Metab. 2003 Feb;88(2):642-9.

Bachrach LK, Hastie T, Wang MC, Narasimhan B, Marcus R. Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab. 1999 Dec;84(12):4702-12.

Gilsanz V, Skaggs DL, Kovanlikaya A, Sayre J, Loro ML, Kaufman F, Korenman SG. Differential effect of race on the axial and appendicular skeletons of children. J Clin Endocrinol Metab. 1998 May;83(5):1420-7.

Abrams SA, O'brien KO, Liang LK, Stuff JE. Differences in calcium absorption and kinetics between black and white girls aged 5-16 years. J Bone Miner Res. 1995 May;10(5):829-33.

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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.

Han ZH, Palnitkar S, Rao DS, Nelson D, Parfitt AM. Effects of ethnicity and age or menopause on the remodeling and turnover of iliac bone: implications for mechanisms of bone loss. J Bone Miner Res. 1997 Apr;12(4):498-508. Erratum in: J Bone Miner Res 1999 Apr;14(4):660.

Cauley JA, Wampler NS, Barnhart JM, Wu L, Allison M, Chen Z, Hendrix S, Robbins J, Jackson RD; Women's Health Initiative Observational Study. Incidence of fractures compared to cardiovascular disease and breast cancer: the Women's Health Initiative Observational Study. Osteoporos Int. 2008 Dec;19(12):1717-23. Epub 2008 Jul 16.

Cauley JA, Palermo L, Vogt M, Ensrud KE, Ewing S, Hochberg M, Nevitt MC, Black DM. Prevalent vertebral fractures in black women and white women. J Bone Miner Res. 2008 Sep;23(9):1458-67.

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. 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.

Cauley JA, Wu L, Wampler NS, Barnhart JM, Allison M, Chen Z, Jackson R, Robbins J. Clinical risk factors for fractures in multi-ethnic women: the Women's Health Initiative. J Bone Miner Res. 2007 Nov;22(11):1816-26.

Faulkner KA, Cauley JA, Zmuda JM, Landsittel DP, Nevitt MC, Newman AB, Studenski SA, Redfern MS. Ethnic differences in the frequency and circumstances of falling in older community-dwelling women. J Am Geriatr Soc. 2005 Oct;53(10):1774-9.

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.

Schnitzler CM, Mesquita JM. Cortical bone histomorphometry of the iliac crest in normal black and white South African adults. Calcif Tissue Int. 2006 Dec;79(6):373-82. Epub 2006 Dec 8.

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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Mikuls TR, Saag KG, George V, Mudano AS, Banerjee S. Racial disparities in the receipt of osteoporosis related healthcare among community-dwelling older women with arthritis and previous fracture. J Rheumatol. 2005 May;32(5):870-5.

Alam NM, Archer JA, Lee E. Osteoporotic fragility fractures in African Americans: under-recognized and undertreated. J Natl Med Assoc. 2004 Dec;96(12):1640-5.

Looker AC. The skeleton, race, and ethnicity. J Clin Endocrinol Metab. 2002 Jul;87(7):3047-50. Review. No abstract available.

Bell NH, Bilezikian JP, Bone HG 3rd, Kaur A, Maragoto A, Santora AC; MK-063 Study Group. Alendronate increases bone mass and reduces bone markers in postmenopausal African-American women. J Clin Endocrinol Metab. 2002 Jun;87(6):2792-7.

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.

Lau EM, Suriwongpaisal P, Lee JK, Das De S, Festin MR, Saw SM, Khir A, Torralba T, Sham A, Sambrook P. Risk factors for hip fracture in Asian men and women: the Asian osteoporosis study. J Bone Miner Res. 2001 Mar;16(3):572-80.

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Heaney RP. Bone mass, the mechanostat, and ethnic differences. J Clin Endocrinol Metab. 1995 Aug;80(8):2289-90. No abstract available.

Cundy T, Cornish J, Evans MC, Gamble G, Stapleton J, Reid IR. Sources of interracial variation in bone mineral density. J Bone Miner Res. 1995 Mar;10(3):368-73.

Wright NM, Renault J, Willi S, Veldhuis JD, Pandey JP, Gordon L, Key LL, Bell NH. Greater secretion of growth hormone in black than in white men: possible factor in greater bone mineral density--a clinical research center study. J Clin Endocrinol Metab. 1995 Aug;80(8):2291-7.

Looker AC, Johnston CC Jr, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Lindsay RL. Prevalence of low femoral bone density in older U.S. women from NHANES III. J Bone Miner Res. 1995 May;10(5):796-802.

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Baron JA, Barrett J, Malenka D, Fisher E, Kniffin W, Bubolz T, Tosteson T. Racial differences in fracture risk. Epidemiology. 1994 Jan;5(1):42-7.

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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
Study First Received:	April 8, 2011
Last Updated:	July 6, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:

Endocrine System Diseases
MusculoSkeletal System Disease
Hormones
Postmenopausal Women

Bone metabolism
Physiologic Properties
African-Americans

Additional relevant MeSH terms:

Bone Diseases
Bone Diseases, Endocrine
Neoplasms
Endocrine System Diseases
Hypercalcemia
Hyperparathyroidism
Osteoporosis
Musculoskeletal Diseases
Calcium Metabolism Disorders

Metabolic Diseases
Water-Electrolyte Imbalance
Parathyroid Diseases
Bone Diseases, Metabolic
Hormones
Anabolic Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013

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