Dental Implant Study Comparing Two Types of Metals Used for Dental Implants (ZMU)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
Zimmer Dental
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01714024
First received: October 17, 2012
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

The purpose of this research study is to compare the healing differences of two metals (trabecular vs. standard titanium) that are used for dental implants. In addition; investigators will be examine these differences in the gene expression profiles in subjects with three conditions associated with delayed healing: diabetes and osteoporosis.

The study will last at least 11 weeks consisting of 6 appointments. All visits will be carried out at the GO Health Center within the UNC School of Dentistry. Visits will last between 30 minutes to 3 hours depending on the particular visit.

The visits will consist of: Obtaining consent, doing a health history, measuring vital signs, doing dental exams of the teeth and gums, collecting samples of saliva dental radiographs (X-rays), a teeth cleaning, having 4 temporary mini test cylinders placed in areas of the lower jaw where teeth are missing and implant surgery to place up to four permanent implants.


Condition Intervention Phase
Tooth Replacement
Device: Zimmer Trabecular Metal Test Cylinder
Device: Zimmer Titanium Test Cylinder
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Molecular and Cellular Comparison of Bone Inductive Properties Of Trabecular Metal® Vs. Titanium Among Healthy, Diabetic, and Osteopenic Subjects

Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Examination of the molecular pathways to compare osseous healing associated with trabecular metal vs. standard titanium. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Whole transcriptome analysis will be used to collect data from samples from each cohort


Secondary Outcome Measures:
  • Gene expression profiles of trabecular metal verses titanium [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Findings from Affymetrix expression arrays will be used to perform quantitative PCR analyses using SAB Superarrays (SuperArray GEArray), a pathway - focused PCR Array with 96 gene panels to enable a quantitative PCR validation of mRNA levels of specific inflammatory molecules, including enzyme histochemistry


Estimated Enrollment: 36
Study Start Date: October 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy Volunteers
Subjects who are non-diabetic, with no history of smoking within the past two years and no metabolic bone disease diagnosis.
Device: Zimmer Trabecular Metal Test Cylinder
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.
Device: Zimmer Titanium Test Cylinder
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.
Experimental: Diabetic Subjects
Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin.
Device: Zimmer Trabecular Metal Test Cylinder
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.
Device: Zimmer Titanium Test Cylinder
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.
Experimental: Osteopenic Subjects
Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates
Device: Zimmer Trabecular Metal Test Cylinder
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.
Device: Zimmer Titanium Test Cylinder
For all subjects 2 titanium and 2 trabecular 2.9-3.0 mm x 5 mm test cylinders will be implanted in alveolar bone. One of each type will be removed at 2 weeks. The remaining two will be removed at 4 weeks.

Detailed Description:

The plan is to recruit subjects into 3 groups: 1) systemically healthy, 2) subjects with diabetes (ADA classification determined by glycosylated hemoglobin A1C levels), and 3) subjects with osteoporosis (limited to those on either no drugs or oral bisphosphonates only). All subjects recruited will have already been approved and treatment planned for implant placement by non-study personnel to avoid any potential conflict of interest. All subjects will have mandibular radiographs that show edentulous ridge areas that provide enough alveolar ridge space to place two test cylinders (each approximately 2.9-3 x 5mm) on each side of the mandible. One side will have two titanium test cylinders and the contralateral side will have two trabecular metal test cylinders. After placement of these 4 test cylinders, one will be removed contra laterally from each side at weeks 2 and 4 of healing. Thus, by 28 days all test cylinders will be removed.

It has been our experience that each cylinder after removal will contain enough cells to provide approximately 10-20μg of total RNA. This quantity of total RNA is sufficient to run an Affymetrix chip and have enough mRNA for PCR confirmation. Sampling at 3 days after placement is too soon, as it does not provide adequate mRNA for the analysis, since the clot has not become remodeled or adequately organized to be cellular. Thus, by 1 week organization of the osseous healing will have begun and at week 2 it will be beginning to mature. The week 2 sampling time point) will provide us with early molecular kinetics of the healing response to compare the two metal surfaces and the differences in gene expression that may be associated with diabetes and osteoporosis. At weeks 2 and 4 the test cylinders will be removed using a 5.0 mm diameter tissue punch and a 5 mm trephine drill. Investigators will select 18 random patients (6 subjects per group) to provide (two test cylinders for each, 36 samples) for histology. Investigators will use the trephine drill to remove the 4 week test cylinders in all 3 groups of subjects. In all cases, a subject is eligible for this study by being pretreatment planned to receive a permanent implant bilaterally, which will be placed at donor sites. According to the participant's individual treatment plan, after test cylinders are removed, each site will receive an implant using either a standard 4.1 or 4.7 mm tapered screw vent design implant. The removed test cylinders will be briefly rinsed in saline and prepared chair side for either mRNA extraction or for histology.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects must be adult males or females age 21 to 80 years (inclusive).
  • Subjects must be able and willing to follow study procedures and instructions in English.
  • Subjects must have read, understood and signed an informed consent form in English.
  • Subjects must have at least four mandibular implants as their future treatment needs.

Subjects must meet one of the following categories to be considered for enrollment:

  • Group 1 (control): Subjects must be non-diabetic, no history of smoking within the last two years and no metabolic bone disease diagnosis.
  • Group 2 (diabetic): Subjects must have Type 2 diabetes mellitus as diagnosed by a physician or in medication history. The condition must be currently diagnosed and treated by medications and/or insulin. An HbA1C test performed either within past 3 months must be available or one will be done at the first visit by study personnel. Subjects must have no history of smoking within the last two years nor have any diagnosis of metabolic bone disease.
  • Group 3 (Osteoporosis or osteopenia): Subjects must be diagnosed with osteoporosis or osteopenia and must be currently under the care of a physician and treatment with oral bisphosphonates. Subjects must have never had intravenous (IV) bisphosphonates. Subjects in this group must be non-diabetic and no history of smoking within the last 2 years.

Subjects undergoing test cylinder placement should be in adequate periodontal health prior to implant placement. This includes having probing depth ≤ 4 mm for all remaining teeth at the same quadrant of the proposed cylinder placement. Patients with periodontal probing sites with probing depths of up to 5 mm may also be included if bleeding on probing in these sites is absent. Each subject should be considered to be periodontally stable prior to receiving test cylinders.

Exclusion Criteria:

  • Individuals who have a chronic disease with oral manifestations.
  • Individuals who exhibit gross oral pathology.
  • The use of either antibiotics or chronic use of NSAIDs within 1 month prior to screening examination.
  • Individuals that require antibiotic prophylaxis prior to dental treatment.
  • Chronic treatment (i.e. two weeks or more) with any medication known to affect periodontal status (e.g. phenytoin, calcium antagonists, cyclosporine, Coumadin) within 1 month prior to screening examination.
  • Systemic conditions, except diabetes, osteoporosis and osteopenia that are known to affect periodontal status.
  • Individual with uncontrolled parafunctional habits, such as clenching and bruxing on objects, that could adversely impact implant survival
  • Individuals with a history of intravenous bisphosphonates Individuals with active infectious diseases such as hepatitis, HIV or tuberculosis.
  • Individuals with a current tobacco use history.
  • Individuals who are known to be pregnant, breastfeeding or planning to become pregnant within 3 months.
  • Individuals with blood disorders and /or currently taking anticoagulants medications, unless he or she can provide a current International normalized ratio (INR) showing normal (0.8 - 2.0) values.
  • Individuals receiving any therapy known to affect healing, such as high dose corticosteroids, radiation therapy or chemotherapy.
  • Individuals allergic to topical or local anesthesia
  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: NCT01714024

Contacts
Contact: Carol Culver 919-537-3176 Culverc@dentisty.unc.edu
Contact: Sherrill T. Phillips, RDH-BS, CRS 919-537-3422 Sherrill_phillips@dentistry.unc.edu

Locations
United States, North Carolina
General & Oral Health Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Sherrill T. Phillips, RDH-BS, CRS    919-537-3422    Sherrill_phillips@dentistry.unc.edu   
Contact: Wendy Lamm    919-537-3418    Wendy_Lamm@dentistry.unc.edu   
Principal Investigator: Silvana Barros, DDS, PhD         
Principal Investigator: Sompop Bencharit, DDS, MS, PhD         
Sub-Investigator: Roger M. Arce, DDS, MS, PhD         
Sub-Investigator: Christian Brenes, DDS         
Sub-Investigator: Luisito Mendoza, DDS         
Sub-Investigator: Thiago Morelli, DDS, MS         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Zimmer Dental
Investigators
Principal Investigator: Steven Offenbacher, DDS, PhD, MMSc University of North Carolina School of Dentistry
  More Information

Additional Information:
No publications provided

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01714024     History of Changes
Other Study ID Numbers: ZMU 11-2539
Study First Received: October 17, 2012
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Dental
Implant
UNC Dental School
Trabecular Metal
Titanium
Healthy Volunteers
Diabetic
Osteopenic
Bone Inductive Properties
Osseous Healing
GO Health
Offenbacher
Zimmer Dental, Inc.

ClinicalTrials.gov processed this record on October 21, 2014