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NCT Number: NCT00580788

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

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.

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Key information

Conditions

Osteoporosis Bone Diseases Bone Diseases, Metabolic Endocrine System Diseases Humoral Hypercalcemia Of Malignancy Hyperparathyroidism Metabolic Diseases Musculoskeletal Diseases Neoplasms Nutritional and Metabolic Diseases Parathyroid Diseases

Age range

24 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PTHrP (1-36)

Drug

IND # 49,175

Other names: Parathyroid Hormone-related Protein (1-36)

Primary outcomes

  1. 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.

  2. 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

  3. 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

  4. 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

Secondary outcomes

  1. 1,25 Vitamin D

    Time frame: Baseline and Daily through day 8 then at follow-up visit

    pg/ml

  2. 24 Hour Urine Calcium

    Time frame: 24 hours

    mg/gm creatinine collected on day 7 of PTHrP infusion

  3. Tubular Maximum of Phosphorous (TmP/GFR)

    Time frame: daily

    mg/dl calculated from daily second morning void

  4. Serum Amino-terminal Telopeptide of Collagen -1 (sNTX)

    Time frame: Baseline, Daily, and 1 week follow-up

    % change from baseline

  5. Serum Carboxy-terminal Telopeptide of Collagen -1 (sCTX)

    Time frame: Baseline, Daily, and 1 week follow-up

    % change from baseline

  6. Amino-terminal Peptides of Procollagen 1 (P1NP)

    Time frame: Baseline, Daily, and 1 week follow-up

    % change from baseline

  7. Bone Specific Alkaline Phosphatase (BSAP)

    Time frame: Baseline, Daily, and 1 week follow-up

    % change from baseline

  8. Parathyroid Hormone (1-84)

    Time frame: Baseline and Daily

    pg/ml

  9. Fractional Excretion of Calcium

    Time frame: daily

    % calculated from daily second morning void

Sponsors and collaborators

Lead sponsor

University of Pittsburgh

Other

Collaborators

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

Registry information

Official study title

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

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Dec 27, 2007
Registry last updated
Feb 11, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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