The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone

January 31, 2018 updated by: Jill Bashutski, University of Michigan
Good bone healing and bone build-up are necessary for the success of dental implants. Research in animals and humans has shown that a drug, called Forteo, can increase bone build-up and bone strength over time. Forteo has been approved by the Food and Drug Administration (FDA) for use in patients with a condition where bone is broken down and weakened, called osteoporosis. The investigators do not know, however, whether Forteo is effective for use in humans for improving bone healing after implant placement, and whether it will have the same bone-building and bone-strengthening effects as for patients with osteoporosis. This research study is being done to learn what effect 7 weeks of treatment with Forteo will have on bone build-up and strengthening of bone for patients receiving implants.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

A single center, placebo-controlled, double blind parallel study of teriparatide use in patients requiring dental implant therapy is planned. Subjects who qualify based on the inclusion/exclusion criteria will be randomly placed into one of two treatment groups, teriparatide (20 μg/day) or placebo control. Both patients and investigators will be blinded. Serum and gingival crevicular fluid (GCF) samples, radiographs, and a tetracycline-labelled bone core will constitute the main data gathered for analysis. After implant surgery, patients will return at 2 weeks for post-operative care and then at 14 weeks for an implant impression and again at 16 weeks to receive the final restoration. Twelve months after implant placement, patients will be seen for a follow-up exam and standardized radiograph to ensure proper healing.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 2

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
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Michigan Center for Oral Health Research

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

30 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age range 30-85 yrs
  • Sex: male and female (female subjects must be postmenopausal, surgically sterilized or utilizing birth control or abstinence throughout the period of Teriparatide administration)
  • Subjects must be able and willing to follow study procedures and instructions;
  • Subjects must have read, understood and signed an informed consent form;
  • Subjects must have a need for the replacement of at least one tooth in the mandibular premolar/molar region with at least 12 months since the tooth extraction.
  • Sites must be adaptable for dental implant placement without the necessity for grafting.

Exclusion Criteria:

  • Subjects under 30 years or over 85 years of age,
  • Female subjects who are pregnant, lactating, or female subjects who are of childbearing potential who are not using contraceptives,
  • Subjects with metabolic bone diseases such as Paget's disease, hypercalcemia (mild to moderate hypocalcemia is acceptable for entry into the study), moderate to severe vitamin D3 abnormalities (If vitamin D levels are below 16 ng/ml and patient exhibits interest, dietary supplementation will be suggested and levels re-evaluated after 4 weeks and reconsidered for inclusion at that time), any other metabolic bone diseases including osteoporosis,
  • Subjects with prior radiation therapy, bone metastases or other skeletal malignancy,
  • Subjects on medications that would affect bone metabolism,
  • Subjects with growth hormone deficiency,
  • Subjects with uncontrolled diabetes, sprue, inflammatory bowel disease or other disorders that would affect calcium absorption
  • Subjects that are heavy smokers (> 1 pack/d),
  • Subjects with tetracycline sensitivity or allergy,
  • Subjects on bisphosphonates,
  • Subjects with any form of kidney disease including kidney stones (urolithiasis and nephrolithiasis),
  • Subjects with known allergies to tetracycline and/or demeclocycline,

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Teriparatide
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Drug: Teriparatide
20ug per day,via subcutaneous injection, for 7 weeks
Other Names:
  • Forteo
Placebo Comparator: Control
demeclocycline HCl (150 mg, four times per day for 3d) followed by a 12 day intermission then 3 more days of demeclocycline HCl (150 mg, four times per day). One day after the last demeclocycline dosage, subjects will be instructed to self-administer teriparatide (or placebo) for 7 weeks. Twenty-five days after the last demeclocycline dosage, subjects will begin their second set of tetracycline labels:(250 mg, four times per day) for three days, followed by 12 days off, and then repeat another 3 days of tetracycline HCl (250 mg, four times per day). On day of the last teriparatide (or placebo) injection, subjects will present for bone core removal and dental implant placement.
Drug: Placebo
20ug per day, self administered injection, for 7 weeks
Other Names:
  • carrier

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone Formation Rate
Time Frame: 10 weeks
To determine the impact of PTH on bone quality and bone turnover in the oral cavity. The primary outcome variable will be bone formation rate.
10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone Turnover (Mineral Apposition Rates)
Time Frame: 10 weeks
Bone turnover was assessed indirectly by bone histomorphometry using the following abbreviations: Mineral Apposition Rate (MAR): Distance between 2 fluorochrome markers that comprise a double label on the surfaces of cancellous bone measured at an average of 4 equally-spaced sites per double label. These measurements will be performed on 20 double fluorochrome labels per bone and the average divided by the time between the midpoints of the two labeling periods. MAR serves as an index of osteoblast activity. Reported for cancellous (Cn), endocortical (Ec) at baseline (pre-drug intervention, listed as "first set") and at the end of drug intervention ("second set"). "First set" refers to baseline information (pre-drug), and "second set" refers to data evaluated at the end of the drug administration phase. Periosteal (Ps) data and Ec.Mar Endocortical MAR "second set" was reviewed but no analyzable labeling was noted and so this data is not reported.
10 weeks
Bone Turnover: Cortical Tissue Area
Time Frame: 10 weeks

Bone turnover was assessed indirectly by evaluating cellular parameters of PTH action (i.e. numbers of osteoblasts, osteoclasts, apoptotic osteoblasts). The methods used to obtain the outcomes described below were bone histomorphometry using the following abbreviation:

Ct.T.Ar: Ct Cort(ex)(ical) Tissue Area (2D)b "First set" refers to baseline pre-drug data and "second set" was taken at the end of the drug administration phase.
10 weeks
Bone Turnover: Bone Perimeter Length
Time Frame: 10 weeks

Bone histomorphometry was used to assess bone perimeter length in mm as follows:

Cn.Pm cancellous: Cancellous Bone Perimeter Ec.Pm: endocortical bone perimeter Ps.Pm: Periosteal Periosteal bone perimeter
10 weeks
Bone Turnover: Bone Percentages
Time Frame: 10 weeks

Oc.S/BS cancellous: Osteoclast suface divided by bone surface. Osteoclastic surface as percent of total bone surface in cancellous bone. Percent cancellous bone perimeter with osteoclasts (large, multinuclear, TRAP positive cells).

OS/BS cancellous: Osteoid surface divided by bone surface. Percentage of cancellous bone perimeter covered with osteoid.

Oc.S/BS endocortical: Osteoclastic surface as percent of total bone surface in endocortical bone.

OS/BS endocortical: Percentage of endocortical bone perimeter covered with osteoid.

Oc.S/BS Periosteal: Osteoclastic surface as percent of total bone surface in periosteal bone.

Ob.S/BS Periosteal: Percent periosteal bone perimeter with osteoid and adjacent osteoblasts, identified as plump cells with a single, eccentric nucleus and a pale-staining golgi apparatus. Osteoblast Surface divided by bone surface in periosteal bone.

OS/BS Periosteal: Percentage of periosteal bone perimeter covered with osteoid.
10 weeks

Collaborators and Investigators

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

Sponsor

University of Michigan

Collaborators

Eli Lilly and Company

Investigators

  • Principal Investigator: Jill Bashutski, DDS, MS, Faculty

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

February 1, 2011

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

January 18, 2011

First Submitted That Met QC Criteria

January 18, 2011

First Posted (Estimate)

January 19, 2011

Study Record Updates

Last Update Posted (Actual)

February 7, 2018

Last Update Submitted That Met QC Criteria

January 31, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00042770

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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