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

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ClinicalTrials.gov Identifier: NCT01279187
Recruitment Status : Terminated (Study was terminated due to patient complications unrelated to study drugs)
First Posted : January 19, 2011
Results First Posted : February 7, 2018
Last Update Posted : February 7, 2018
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Jill Bashutski, University of Michigan

January 18, 2011
January 19, 2011
June 28, 2017
February 7, 2018
February 7, 2018
February 2011
March 2015   (Final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01279187 on ClinicalTrials.gov Archive Site
  • 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.
  • 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.

  • 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

  • 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.

bone turnover [ Time Frame: 10 weeks ]
include serum and GCF parameters of bone turnover, cellular parameters of PTH action (i.e. numbers of osteoblasts, osteoclasts, apoptotic osteoblasts) along with derived outcomes such as; the correlation of systemic serum PINP and bone structure and dynamic indices at baseline; changes in systemic PINP as correlated with local bone formation rates in the mandible; and whether numbers of apoptotic osteoblasts correlate with bone formation rates.
Not Provided
Not Provided
 
The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone
The Impact of Parathyroid Hormone (PTH) on Craniofacial Osseous Regeneration in Bone
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.
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.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Implant
  • Drug: Teriparatide
    20ug per day,via subcutaneous injection, for 7 weeks
    Other Name: Forteo
  • Drug: Placebo
    20ug per day, self administered injection, for 7 weeks
    Other Name: carrier
  • 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.
    Intervention: Drug: Teriparatide
  • 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.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
27
30
November 2015
March 2015   (Final data collection date for primary outcome measure)

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,
Sexes Eligible for Study: All
30 Years to 85 Years   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01279187
HUM00042770
No
Not Provided
Plan to Share IPD: No
Jill Bashutski, University of Michigan
University of Michigan
Eli Lilly and Company
Principal Investigator: Jill Bashutski, DDS, MS Faculty
University of Michigan
January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP