One Week Comparison Study of PTH and PTHrP Infusions

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 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: April 25, 2014
Last verified: April 2014
  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:


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 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:
  • 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 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:
  • 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

  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 (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

Contacts
Contact: Linda Prebehalla, RN 412-864-3265 lprebeh@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
Contact: Mara J Horwitz, MD    412-692-2848    horwitzm@pitt.edu   
Principal Investigator: Mara J Horwitz, MD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Mara J. Horwitz, MD University of Pittsburgh
  More Information

Publications:

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: April 25, 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:
Bone Diseases
Bone Diseases, Endocrine
Bone Diseases, Metabolic
Osteoporosis
Hyperparathyroidism
Hypercalcemia
Paraneoplastic Syndromes
Endocrine System Diseases
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
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014