7 Day Continuous Parathyroid Hormone IV Infusion

This study has been completed.
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Mara Horwitz, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00377312
First received: September 14, 2006
Last updated: March 18, 2016
Last verified: March 2016
  Purpose

Study consists of an eight day inpatient visit on the General Clinical Research Center. The investigators' specific aims are to:

  1. To define the maximum safe dose of a seven day continuous administration of parathyroid hormone [PTH(1-34)] in healthy human volunteers.
  2. To estimate the effect of a seven day continuous administration of parathyroid Hormone (PTH) in escalating doses on vitamin D metabolism, markers of bone turnover and fractional excretion of urine.

Condition Intervention Phase
Osteoporosis
Bone Diseases, Endocrine
Hyperparathyroidism
Drug: Parathyroid Hormone (1-34)
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Official Title: Determining the Maximal Safe Dose of a Continuous Infusion of Parathyroid Hormone(1-34): Effects on Bone Formation

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Participants With Dose Limiting Toxicity [ Time Frame: 12 hours after the infusion was started then q 8 hours for 7 days ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    mg/dl


Secondary Outcome Measures:
  • 1,25 Vitamin D [ Time Frame: baseline, daily up to Day 8 and follow-up ] [ Designated as safety issue: No ]
    pg/ml

  • Parathyroid Hormone (1-84) [ Time Frame: baseline, daily up to Day 8 and follow-up ] [ Designated as safety issue: No ]
    pg/ml

  • Fractional Excretion of Calcium [ Time Frame: baseline and daily ] [ Designated as safety issue: No ]
    % = (S Creatinine X U Calcium)/(S Calcium X U Creatinine)

  • 24 Hour Urine Calcium [ Time Frame: 24 hours period from Day 7 to Day 8 ] [ Designated as safety issue: No ]
    mg/gm creatinine

  • Tubular Maximum for Phosphorous [ Time Frame: baseline and daily ] [ Designated as safety issue: No ]
    mg/dl

  • Serum Amino-terminal of Collagen- (sNTX) [ Time Frame: baseline, daily, one week follow-up ] [ Designated as safety issue: No ]
    % change from baseline

  • Serum Carboxy-terminal of Collagen- 1(sCTX) [ Time Frame: baseline, daily, one week follow-up ] [ Designated as safety issue: No ]
    % change from baseline

  • Amino-terminal Peptides of Procollagen- 1(P1NP) [ Time Frame: baseline, daily, one week follow-up ] [ Designated as safety issue: No ]
    % change from baseline

  • Bone Specific Alkaline Phosphatase (BSAP) [ Time Frame: baseline, daily, one week follow-up ] [ Designated as safety issue: No ]
    % change from baseline


Enrollment: 11
Study Start Date: September 2006
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Parathyroid Hormone (PTH) (1-34) 2 picomols/kg/hr for one week.
Drug: Parathyroid Hormone (1-34)
PTH(1-34) IV given over a one week period
Other Name: IND 60,979
Experimental: Group 2
Parathyroid Hormone (PTH) (1-34)4 picomols/kg/hr for one week.
Drug: Parathyroid Hormone (1-34)
PTH(1-34) IV given over a one week period
Other Name: IND 60,979

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   24 Years to 35 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy Caucasian, Hispanic or Asian subjects
  • Males and Females
  • Non-smoker
  • Ages 24 - 35 years old
  • Subjects will be recruited either from the employee pool of the University of Pittsburgh or the University of Pittsburgh Medical Center (UPMC), or the general population living in the vicinity.
  • Participation in this study by an employee or a potential employee at the University of Pittsburgh or UPMC has no effect on their employment or potential employment.
  • Participants in the study will be required to discontinue all vitamins and health food supplements two weeks prior to the study.

Exclusion Criteria:

  • Cardiac, hypertensive, vascular, renal (serum creatinine of >1.5), pulmonary, endocrine, musculoskeletal, hepatic, hematologic or malignant or rheumatologic disease
  • Body Mass Index (BMI) > 30,
  • Anemia (hematocrit less than 36% in women, less than 40% in men),
  • Pregnancy (all women will have a urine pregnancy test performed immediately before starting the study and must not be pregnant)
  • Significant alcohol or drug abuse or
  • Baseline hypotension (systolic blood pressure less than 90 mm/Hg).
  • Subjects will be excluded for abnormal levels of any of the screening labs including: ionized and total serum calcium, phosphorus, creatinine, albumin, 25-hydroxyvitamin D, and PTH. Pregnancy
  • Subjects taking any chronic medications except oral contraceptives and stable doses of thyroid hormone, or those who have received any investigational drug in past 90 days will be excluded from the study.
  • Subjects may not participate in this study more than once.
  • Any subject who has previously received PTH or PTHrP, a related peptide, may not participate in this study.

Minority Inclusion/Exclusion Statement: We will not include African-Americans because this group has been demonstrated by a number of investigators to display resistance to PTH, and may create wider statistical variation and a need for larger numbers of study subjects per group.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00377312

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh,, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Mara J. Horwitz, MD University of Pittsburgh
  More Information

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mara Horwitz, Associate Professor of Medicne, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00377312     History of Changes
Other Study ID Numbers: 0606127  R01DK073039 
Study First Received: September 14, 2006
Results First Received: April 25, 2014
Last Updated: March 18, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University of Pittsburgh:
Endocrine System Diseases
MusculoSkeletal System Disease
Hormone
Physiologic Properties

Additional relevant MeSH terms:
Bone Diseases
Bone Diseases, Endocrine
Bone Diseases, Metabolic
Osteoporosis
Hyperparathyroidism
Endocrine System Diseases
Musculoskeletal Diseases
Parathyroid Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2016