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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Determining the Maximal Safe Dose of a Continuous Infusion of Parathyroid Hormone-related Protein(1-36): Effects on Bone Formation

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: University of Pittsburgh

Current Primary Outcome:

  • Dose Limiting Toxicity (DLT) [ Time Frame: 12 hours after the infusion was started then q 8 hours for 7 days ]
    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 ]
    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 ]
    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 ]
    mg/dl


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

Current Secondary Outcome:

  • 1,25 Vitamin D [ Time Frame: Baseline and Daily through day 8 then at follow-up visit ]
    pg/ml
  • 24 Hour Urine Calcium [ Time Frame: 24 hours ]
    mg/gm creatinine collected on day 7 of PTHrP infusion
  • Tubular Maximum of Phosphorous (TmP/GFR) [ Time Frame: daily ]
    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 ]
    % change from baseline
  • Serum Carboxy-terminal Telopeptide of Collagen -1 (sCTX) [ Time Frame: Baseline, Daily, and 1 week follow-up ]
    % change from baseline
  • Amino-terminal Peptides of Procollagen 1 (P1NP) [ Time Frame: Baseline, Daily, and 1 week follow-up ]
    % change from baseline
  • Bone Specific Alkaline Phosphatase (BSAP) [ Time Frame: Baseline, Daily, and 1 week follow-up ]
    % change from baseline
  • Parathyroid Hormone (1-84) [ Time Frame: Baseline and Daily ]
    pg/ml
  • Fractional Excretion of Calcium [ Time Frame: daily ]
    % calculated from daily second morning void


Original Secondary Outcome: Measurement of vitamin D levels, markers of bone metabolism and fractional excretion of calcium measurements. [ Time Frame: One week ]

Information By: University of Pittsburgh

Dates:
Date Received: December 20, 2007
Date Started: January 2008
Date Completion:
Last Updated: February 9, 2016
Last Verified: February 2016