One Week Comparison Study of PTH and PTHrP Infusions

This study has been withdrawn prior to enrollment.

Sponsor:

Information provided by (Responsible Party):

Mara Horwitz, University of Pittsburgh

ClinicalTrials.gov Identifier:

NCT01333267

First received: April 8, 2011

Last updated: December 3, 2014

Last verified: December 2014

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: African American Health Anabolic Steroids Bone Diseases Hormones

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 ]


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

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)

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)

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 (Adult)
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 (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

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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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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:	December 3, 2014
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:


Osteoporosis Hyperparathyroidism Hypercalcemia Bone Diseases 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

ClinicalTrials.gov processed this record on September 29, 2016

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