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

February 9, 2016 updated by: Mara Horwitz, University of Pittsburgh

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

24 years to 35 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Parathyroid Hormone-related Protein (1-36)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 hours after the infusion was started then q 8 hours for 7 days
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
12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
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
12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
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
12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Primary Completion (ACTUAL)

December 1, 2009

Study Completion (ACTUAL)

December 1, 2009

Study Registration Dates

First Submitted

December 20, 2007

First Submitted That Met QC Criteria

December 26, 2007

First Posted (ESTIMATE)

December 27, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

February 11, 2016

Last Update Submitted That Met QC Criteria

February 9, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO07040081
  • R01DK073039 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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