rhPTH Therapy for Low Turnover Bone Fragility

January 8, 2016 updated by: University of Chicago

Effect of 12 Months Treatment With rhPTH on Calcium Balance, Bone Turnover, Bone Mineral Density, and Bone Micro-architecture in Patients With Fractures Associated With Low Bone Turnover and Sclerosing Bone Disorders

The purpose of this study is to determine how treatment with a new medication, recombinant human parathyroid hormone (rhPTH) affects calcium balance and bone strength.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Subjects will have had a bone biopsy to definitively determine low bone turnover. Subjects and the treating doctor decide that treatment with rhPTH (recombinant human parathyroid hormone) is optimal before admission into the study. During the study, subjects will have several tests that will clarify how rhPTH is affecting calcium metabolism and bone properties. All of the studies will be performed in the University of Chicago General Clinical Research Center (GCRC).

To examine the effects of PTH (parathyroid hormone) on calcium metabolism, subjects will be admitted to the GCRC for 3 days in the beginning of the study. Subjects will have a plastic needle inserted into a vein to enable the nurses to draw your blood repeatedly without having to stick you every time. Subjects will have 120 mL (about 8 tablespoons) of blood drawn during the 3 day period. Subjects will be allowed to choose the food from the regular hospital menu but the amount of calcium from the diet will be the same during each day that you spend in the GCRC. The first day will be used to observe calcium balance without medication while the subsequent 2 days will be used to determine how calcium balance changes in response to the medication rhPTH. Subjects will take the medication in the morning, before breakfast - this will be considered time 0. During all 3 days, blood will be taken at 0, 2, 4, 6, 8, 12, 16, and 20 hours for examination of serum calcium and at 0, 4 and 12 hours for measurement of PTH (that is produced by your body).

On the first and 3rd day all the urine will be collected to measure how much calcium is lost in the urine.

After Subjects have received the medication for 3 months they will again be admitted to the GCRC, this time for 2 days during which they will continue to take the medication with the same measurements as on the last 2 days of the first admission. The same admission will be repeated after 12 months of treatment. During each of these admissions, you will have 80 mL (about 5 ½ tablespoons) of blood drawn.

In addition to these 3 inpatient stays in the CRC, subjects will also have several tests as an outpatient. The tests will be used to evaluate the effect of rhPTH on the bone. To this end, you will have 3 types of tests.

  1. To evaluate the bone turnover (activity of bone cells) subjects will have blood and urine collected for measurement of biochemical markers of bone turnover (chemicals in the blood and urine that reflect the activity of bone cells) measured before and at 1, 2, 3, 6, 9, and 12 months. Subjects will have 10 mL (about 2 teaspoons) of blood drawn at each of these visits.
  2. To evaluate changes in the bone density subjects will have bone density test of the lumbar spine, hip, heel and wrist measured every 3 months for 12 months.
  3. To evaluate changes in the architecture or structure of the bone subjects will have 2 tests. First, the heel images that are obtained during the bone density test (under #2) will be subjected to radiographic texture analysis. This is a method of computerized analysis of the pattern of bone radiographic images which is supposed to differentiate between strong and weak bone based on the difference in the radiographic texture. The second test will be a bone biopsy. A bone biopsy involves inserting a needle through the skin and directly into the bone to obtain a piece of the bone of 1 cm (less than ½ inch) in length and 0.3 cm (1/10 inch) in diameter. Before this biopsy needle is inserted a numbing medication is injected to prevent pain during the procedure. You will also receive a medication through the vein so that you will be almost asleep during the procedure (intravenous sedation). Most people only experience minor pain for a few days after the biopsy. Subjects will have had the first bone biopsy before enrolling into this study. A second bone biopsy will be performed after 12 months of treatment with rhPTH.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • 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

    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago

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

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • :patients with history of increased bone fragility by BMD criteria (T score > -1). In addition, the subjects will be enrolled only if they have clear evidence of low bone turnover as indicated by low normal levels of biochemical markers of bone turnover and finding of low bone turnover on bone biopsy. Each subject and his/her treating physician will have agreed that the rhPTH is the best treatment for the patient. Treatment with rhPTH will be considered only if the bone histomorphometry reveals a low turnover state and excludes other known forms of bone disease such as osteomalacia.

Exclusion Criteria:

  • Subjects who are pregnant or younger than 20 will be excluded. Subjects cannot have osteoporosis

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: rhPTH
Subjects will be treated rhPTH for 12 months
Subjects will be treated with rhPTH for 12 months.
Other Names:
  • Recombinant Human Parathyroid Hormone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To describe the acute effects of rhPTH administration on calcium balance.
Time Frame: The effects on calcium balance will be examined at the beginning, after 3 months, and after 12 months of treatment with rhPTH.
The effects on calcium balance will be examined at the beginning, after 3 months, and after 12 months of treatment with rhPTH. The rational for examining calcium balance at these three time points is that (at least in patients wit osteoporosis treated with PTH) the initial response is primarily an increase in bone formation; at 3 months there is also a proportionate increase in bone resorption; and at 12 months there is an established general increase in bone turnover.
The effects on calcium balance will be examined at the beginning, after 3 months, and after 12 months of treatment with rhPTH.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To examine the effect of 12 months of therapy with rhPTH on bone density, bone turnover and bone micro-architecture.
Time Frame: Bone density will be measured at 0, 3, 6, and 12 months
Bone density will be measured at 0, 3, 6, and 12 months in the lumbar spine, proximal femur, and distal radius using Lunar Prodigy, and in the calcaneus using Lunar PIXI (both from GE Medical Systems, Madison, Wisconsin).
Bone density will be measured at 0, 3, 6, and 12 months

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Tamara Vokes, MD, University of Chicago

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

February 1, 2003

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

September 1, 2005

First Submitted That Met QC Criteria

September 2, 2005

First Posted (Estimate)

September 5, 2005

Study Record Updates

Last Update Posted (Estimate)

January 12, 2016

Last Update Submitted That Met QC Criteria

January 8, 2016

Last Verified

January 1, 2016

More Information

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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