Alveolar Bone Changes in Diabetes (ABCD) Study

Diabetes Mellitus Clinical Trial

— ABCD  

Official title:

Placement of Hydrophilic TiZr Implants to Enhance Implant Survival in Diabetic Patients: A Prospective, Two-arm, Cohort Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02395315
• Other study ID #: Tamirshalev
• Status: Completed
• Start date: December 2015
• Est. completion date: November 7, 2021

Study information

• Verified date: March 2022
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Type 2 Diabetes Mellitus (DM) is a very prevalent metabolic disorder in the adult population affecting roughly 17.7 million people in the US alone. The harmful effect of DM on implant integration and survival has been attributed to vascular complications in the alveolar bone that lead to compromised blood supply and decreased bone density. Nonetheless, the specific detrimental effects of DM in the alveolar bone have not been investigated in humans.

People with DM generally lose more teeth than persons without diabetes, but implant placement in not well controlled diabetics is not routinely performed due to the lack of relevant evidence and the risk for implant failure and associated complications. Chemically modified, micro-rough, hydrophilic (SLActive®) titanium implant surfaces have been shown to accelerate osseointegration of dental implants placed in diabetic animals. It has been hypothesized that this enhanced biologic response is due to the biocompatibility and hydrophilicity of the surface that actively attracts blood and is populated by progenitor cells, and growth factors that improve stromal cell differentiation.

Hypotheses:

It is hypothesized that hyperglycemia results in compromised vascularity in the mandible. Thus, hydrophilic TiZr implant surfaces (Roxolid®) that actively attract fluids and possess excellent osteoconductive properties, may enhance peri-implant bone response in diabetic patients to levels comparable to well-controlled diabetics.

Description:

A high level of evidence exists to support the placement of implants in type 2 diabetics with glucosylated hemoglobin (HbA1c) levels within the normoglycemic range. Less information is available for the integration of implants placed in diabetics that cannot achieve good glycemic control, who may represent up to 50% of the diabetic patient population. Recent data from the medical literature have unveiled the deleterious effect of uncontrolled diabetes mellitus (DM) on the bone marrow. The microvascular alterations of DM on skeletal bones lead to microangiopathy, reduced blood flow and fatty degeneration in the bone marrow. Nascent theories that are founded upon the observation of increased levels of soluble osteoprotegerin (OPG) levels in uncontrolled DM implicate disruption of RANKL/OPG signaling as a potential pathway for the diabetes- related bone alterations. Nonetheless, no data is currently available on the pathophysiology of the alveolar bone in patients with DM.

It is hypothesized that 1) hyperglycemia results in compromised vascularity in the mandible, thus 2) hydrophilic TiZr implant surfaces (Roxolid®) that actively attract fluids and possess excellent osteoconductive properties, may enhance peri-implant bone response in not well-controlled diabetics (NCD) to levels comparable to well-controlled diabetics (WCD). We further hypothesize that the expected decreased RANKL/OPG ratio in NCD versus WCD will not recover during post-surgery bone remodeling. To assess our hypotheses, we will recruit n=21 type II WCD (HbA1c≤7.0%) and n=21 type II NCD (7.5%

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: November 7, 2021
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

Adult patients aged 18-85 years with diagnosed DM2.

History of DM2 for at least two years prior to enrollment.

At least one edentulous site in the canine or posterior mandible regions.

HbA1c >7.5% & <10% for enrollment in the test group.

HbA1c = 7.0% for enrollment in the control group.

Available for follow up at 12 months.

Exclusion Criteria:

Mandibular incisor sites that will not allow bone core retrieval due to limited alveolar bone width (ridge width <5mm, height <10mm) as confirmed by pre-operative CBCT.

Smokers: current, or ex-smokers with <2 years cessation.

Active periodontal disease.

Medications that affect bone healing (e.g. bisphosphonates or chronic steroids).

Patients who are carriers of transmissible disease(s) that may unnecessarily expose laboratory personnel to risks.

Participants with a physician-diagnosed osteoporosis (Z-score = -2).

Females during pregnancy or lactation and females that plan to become pregnant in the following year.

Patients that will not agree to participate in this study or sign the consent form.

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

Device:
• Well-controlled diabetic (WC)
Each individual will receive one implant (4.1 Titanium-Zirconia, hydrophilic-Roxolid), that will be placed in the posterior mandible.
• Poorly controlled diabetics (PC)
Each individual will receive one implant (4.1 Titanium-Zirconia, hydrophilic-Roxolid), that will be placed in the posterior mandible.

Locations

Country	Name	City	State
United States	University of Texas	Houston	Texas
United States	University of Minnesota Advanced Education in Periodontology	Minneapolis	Minnesota
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota	University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Differences in alveolar bone mineralization	Comparison of bone mineralization between the two cohorts via histomorphometric measurement of vital bone percentage at the time of implant surgery	Baseline (intra-operative bone sample)
Other	ISQ values as a surrogate for implant stability	Recording of the ISQ values (Osstel) and maximum insertion torque during implant placement as surrogates for primary implant stability.	Time of implant surgery-36 months
Other	Implant survival and success assessment at 3-months, 6-months, 1-year and 3-years post-loading	Implant survival and success assessment at 3-months, 6-months, 1-year and 3-years post-loading	3 years
Other	Marginal bone level assessment	Assessment of marginal bone level maintenance around the implants at 3-months, 6-months, 1-year and 3-years post-loading. Periapical radiographs will be obtained using a paralleling technique with customized film holders will be obtained at baseline	3 years
Other	Implant surgery-related complications	Short-term soft tissue and implant-related complications associated with implant surgery recorded at every post-op visit up to 3-months post-surgery	3 months
Primary	Differences in alveolar bone vascularity among well-controlled and not well-controlled diabetic patients.	The difference between alveolar bone vascularity of well-controlled and not well-controlled diabetic patients by immunostaining	Baseline (intra-operative bone sample)
Secondary	RANK-L to OPG ratio	A comparison between RANK-L to OPG ratio to determine the state of bone remodeling in each cohort.	Baseline to 8 weeks