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

University of Pittsburgh

Status and phase: Completed; Early Phase 1

Conditions: Osteoporosis; Hyperparathyroidism; Humoral Hypercalcemia of Malignancy

Treatments: Drug: PTHrP (1-36)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00580788

PRO07040081

R01DK073039 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 14 patients

Sex: All

Ages: 24 to 35 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

14 participants in 4 patient groups

PTHrP(1-36) 2 pmol/kg/hr

Experimental group

Description:

PTHrP(1-36) at 2 picomoles/kg/hr for one week.

Treatment:

Drug: PTHrP (1-36)

PTHrP (1-36) 4 pmol/kg/hr

Experimental group

Description:

PTHrP(1-36) at 4 picomoles/kg/hr for one week.

Treatment:

Drug: PTHrP (1-36)

PTHrP(1-36) 5 pmol/kg/hr

Experimental group

Description:

PTHrP(1-36) at 5 picomoles/kg/hr for one week.

Treatment:

Drug: PTHrP (1-36)

PTHrP(1-36) 6 pmol/kg/hr

Experimental group

Description:

PTHrP(1-36) at 6 picomoles/kg/hr for one week.

Treatment:

Drug: PTHrP (1-36)