Clinical trial NCT00580788: One Week Parathyroid Hormone-related Protein (PTHrP) IV Dose Escalation Study
Official title: Determining the Maximal Safe Dose of a Continuous Infusion of Parathyroid Hormone-related Protein(1-36): Effects on Bone Formation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Osteoporosis
Humoral Hypercalcemia of Malignancy
Hyperparathyroidism
Keywords: Endocrine System Diseases
MusculoSkeletal System Diseases
Hormones
Malignancy
Postmenopausal Women
Bone metabolism
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2007-12-27
Enrollment: 14
Sex: ALL
Minimum age (years): 24
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

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 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 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

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: 12 hours after the infusion was started then q 8 hours for 7 days
measure: Total Serum Calcium
timeFrame: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
measure: Ionized Serum Calcium
timeFrame: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
measure: Serum Phosphorous
timeFrame: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
Secondary outcomes:
measure: 1,25 Vitamin D
timeFrame: Baseline and Daily through day 8 then at follow-up visit
measure: 24 Hour Urine Calcium
timeFrame: 24 hours
measure: Tubular Maximum of Phosphorous (TmP/GFR)
timeFrame: daily
measure: Serum Amino-terminal Telopeptide of Collagen -1 (sNTX)
timeFrame: Baseline, Daily, and 1 week follow-up
measure: Serum Carboxy-terminal Telopeptide of Collagen -1 (sCTX)
timeFrame: Baseline, Daily, and 1 week follow-up
measure: Amino-terminal Peptides of Procollagen 1 (P1NP)
timeFrame: Baseline, Daily, and 1 week follow-up
measure: Bone Specific Alkaline Phosphatase (BSAP)
timeFrame: Baseline, Daily, and 1 week follow-up
measure: Parathyroid Hormone (1-84)
timeFrame: Baseline and Daily
measure: Fractional Excretion of Calcium
timeFrame: daily
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Mara J Horwitz, MD
role: PRINCIPAL_INVESTIGATOR
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