One Week Parathyroid Hormone-related Protein (PTHrP) IV Dose Escalation Study

This study has been completed.
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Mara Horwitz, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00580788
First received: December 20, 2007
Last updated: February 9, 2016
Last verified: February 2016
  Purpose
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, that can be given safely over one week. The investigators plan to infuse low doses of intravenous PTHrP 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 on markers of bone turnover, and plasma 1,25 (OH)2 vitamin D regulation in healthy human volunteers.

Condition Intervention Phase
Osteoporosis
Humoral Hypercalcemia of Malignancy
Hyperparathyroidism
Drug: PTHrP (1-36)
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Official Title: Determining the Maximal Safe Dose of a Continuous Infusion of Parathyroid Hormone-related Protein(1-36): Effects on Bone Formation

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) [ Time Frame: 12 hours after the infusion was started then q 8 hours for 7 days ] [ Designated as safety issue: Yes ]
    DLT was defined as achieving one major criterion or two minor criteria rated at ≥ 2 on a scale of 0-5. The major criteria were defined as symptomatic orthostatic hypotension (systolic BP fall >30 mm/hg), tachycardia (pulse > 120), hypertension (systolic BP >160 mm/hg on 2 occasions), hypercalcemia (serum calcium ≥ 12 mg/dl), and hypophosphatemia (serum phosphorous < 1.5 mg/dl). Minor criteria included symptoms such as flushing, nausea, abdominal or muscle cramps, dizziness, lightheadedness, palpitations, etc.

  • Total Serum Calcium [ Time Frame: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete ] [ Designated as safety issue: Yes ]
    mg/dl

  • Ionized Serum Calcium [ Time Frame: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete ] [ Designated as safety issue: Yes ]
    mg/dl

  • Serum Phosphorous [ Time Frame: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete ] [ Designated as safety issue: Yes ]
    mg/dl


Secondary Outcome Measures:
  • 1,25 Vitamin D [ Time Frame: Baseline and Daily through day 8 then at follow-up visit ] [ Designated as safety issue: No ]
    pg/ml

  • 24 Hour Urine Calcium [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    mg/gm creatinine collected on day 7 of PTHrP infusion

  • Tubular Maximum of Phosphorous (TmP/GFR) [ Time Frame: daily ] [ Designated as safety issue: No ]
    mg/dl calculated from daily second morning void

  • Serum Amino-terminal Telopeptide of Collagen -1 (sNTX) [ Time Frame: Baseline, Daily, and 1 week follow-up ] [ Designated as safety issue: No ]
    % change from baseline

  • Serum Carboxy-terminal Telopeptide of Collagen -1 (sCTX) [ Time Frame: Baseline, Daily, and 1 week follow-up ] [ Designated as safety issue: No ]
    % change from baseline

  • Amino-terminal Peptides of Procollagen 1 (P1NP) [ Time Frame: Baseline, Daily, and 1 week follow-up ] [ Designated as safety issue: No ]
    % change from baseline

  • Bone Specific Alkaline Phosphatase (BSAP) [ Time Frame: Baseline, Daily, and 1 week follow-up ] [ Designated as safety issue: No ]
    % change from baseline

  • Parathyroid Hormone (1-84) [ Time Frame: Baseline and Daily ] [ Designated as safety issue: No ]
    pg/ml

  • Fractional Excretion of Calcium [ Time Frame: daily ] [ Designated as safety issue: No ]
    % calculated from daily second morning void


Enrollment: 14
Study Start Date: January 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PTHrP(1-36) 2 pmol/kg/hr
PTHrP(1-36) at 2 picomoles/kg/hr for one week.
Drug: PTHrP (1-36)
IND # 49,175
Other Name: Parathyroid Hormone-related Protein (1-36)
Experimental: PTHrP (1-36) 4 pmol/kg/hr
PTHrP(1-36) at 4 picomoles/kg/hr for one week.
Drug: PTHrP (1-36)
IND # 49,175
Other Name: Parathyroid Hormone-related Protein (1-36)
Experimental: PTHrP(1-36) 5 pmol/kg/hr
PTHrP(1-36) at 5 picomoles/kg/hr for one week.
Drug: PTHrP (1-36)
IND # 49,175
Other Name: Parathyroid Hormone-related Protein (1-36)
Experimental: PTHrP(1-36) 6 pmol/kg/hr
PTHrP(1-36) at 6 picomoles/kg/hr for one week.
Drug: PTHrP (1-36)
IND # 49,175
Other Name: Parathyroid Hormone-related Protein (1-36)

Detailed Description:
During this research the investigators administer PTHrP to healthy young volunteers in a controlled, continuous intravenous manner. As research subjects complete the week-long study without adverse effects, the dose of PThrP will be increased in later subjects. In the event of a significant adverse effect, immediate action will be taken to reverse it. The investigators want to estimate the effect of a sustainable level of mild hypercalcemia achieved by a week-long intravenous infusion of PTHrP has on vitamin D metabolism, markers of bone turnover and fractional excretion of calcium.
  Eligibility

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

Inclusion Criteria:

  • Healthy caucasian 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 the University of Pittsburgh Medical Center (UPMC) Montefiore

Exclusion Criteria:

  • Pregnancy
  • Any cardiac, renal, pulmonary, endocrine, musculoskeletal, hepatic, hematological, malignant or rheumatologic diseases
  • Body mass index great than 30
  • Anemia
  • Significant alcohol or drug abuse
  • Baseline hypotension or hypertension
  • Abnormal screening labs
  • Use of certain chronic medications excluding oral contraceptives
  • Receiving an investigational drug in the last 90 days
  • Previously receiving PTH or PTHrP
  • African-American race
  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: NCT00580788

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Mara J Horwitz, MD University of Pittsburgh
  More Information

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mara Horwitz, Associate Professor of Medicne, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00580788     History of Changes
Other Study ID Numbers: PRO07040081  R01DK073039 
Study First Received: December 20, 2007
Results First Received: April 25, 2014
Last Updated: February 9, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University of Pittsburgh:
Endocrine System Diseases
MusculoSkeletal System Diseases
Hormones
Malignancy
Postmenopausal Women
Bone metabolism

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

ClinicalTrials.gov processed this record on July 27, 2016