Diabetes MellitusABCDNCT02395315
Alveolar Bone Changes in Diabetes (ABCD) Study
An observational study of Diabetes Mellitus, run by University of Minnesota at 3 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diabetes Mellitus
- Type of treatment
- Medical device
- How many people
- 42 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2015to 7 Nov 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients with diagnosed type II DM exhibiting at least one edentulous site in the posterior mandible or canine region presenting with levels of HbA1c >7.5% \& <10% for enrollment in the PC group and HbA1c ≤ 7.0% for enrollment in the WC group.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Texas
Houston, Texas, 78229-39000
University of Minnesota Advanced Education in Periodontology
Minneapolis, Minnesota, 55455
University of Washington
Seattle, Washington, 98195-7444
About this study
Official title: Placement of Hydrophilic TiZr Implants to Enhance Implant Survival in Diabetic Patients: A Prospective, Two-arm, Cohort Study
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.
Read more
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.
Read the detailed 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%<HbA1c≤10%) seeking implant placement in the mandible. We will collect intra-operative bone specimens at baseline and blood samples to assess bone structural alterations (H\&E stain), microvascular density (immunohistochemistry), bound RANKL/OPG (immunohistochemistry) and serum RANKL/OPG (ELISA). Implant integration and success will be assessed at 3, 6, 12 and 36-months.
Obtained results will give dental researchers new insights into the pathophysiology of the alveolar bone in diabetes and will provide information on the safety and efficacy of implant placement in type II diabetic patients that cannot control their glycemic status. Collectively, this work will pave the way for identifying efficacious implant treatment modalities for persons that live with type II diabetes to alleviate the morbidity associated with tooth loss in this susceptible population group.
- Conditions
- Diabetes Mellitus
- Being tested
- Well-controlled diabetic (WC), Poorly controlled diabetics (PC)
- Keywords
- Diabetes Mellitus, Osseointegration, Bone vascularity, Primary implant stability
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Well-controlled diabetic (WC)Device
Each individual will receive one implant (4.1 Titanium-Zirconia, hydrophilic-Roxolid), that will be placed in the posterior mandible.
Poorly controlled diabetics (PC)Device
Each individual will receive one implant (4.1 Titanium-Zirconia, hydrophilic-Roxolid), that will be placed in the posterior mandible.
| Study group | Role | What they receive |
|---|---|---|
| Well-controlled diabetic (WC) | well-controlled diabetic controls (HbA1c ≤ 7.0%), individuals will receive a single 4.1 Titanium-Zirconia, hydrophilic (Roxolid) implant placed in the posterior mandible, a bone core will be taken for histologic and histomorphometric analysis. Receives: Device: Well-controlled diabetic (WC) | |
| Poorly controlled diabetics (PC) | Poorly controlled diabetics (HbA1c >7.5% \& <10%), individuals will receive a single 4.1 Titanium-Zirconia, hydrophilic (Roxolid) implant placed in the posterior mandible, a bone core will be taken for histologic and histomorphometric analysis. Receives: Device: Poorly controlled diabetics (PC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline (intra-operative bone sample)
Secondary outcomes (1)
RANK-L to OPG ratio
A comparison between RANK-L to OPG ratio to determine the state of bone remodeling in each cohort.
Measured: Baseline to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2015 (estimated)
- Study startDec 2015
- Primary completionAug 2018
- Study completion7 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- University of Washington
- Responsible party
- Sponsor
- Investigators
- George Kotsakis, DDS, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02395315
- Sponsor's protocol ID
- Tamirshalev
- Acronym
- ABCD
- Status last verified
- Mar 2022
- First submitted
- 17 Mar 2015
- Last updated
- 2 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placement of Hydrophilic TiZr Implants to Enhance Implant Survival in Diabetic Patients: A Prospective, Two-arm, Cohort Study
- ClinicalTrials.gov ID
- NCT02395315
- Acronym / sponsor ID
- ABCD / Tamirshalev
- Conditions
- Diabetes Mellitus
- Keywords
- Diabetes Mellitus, Osseointegration, Bone vascularity, Primary implant stability
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- University of Washington
- Study start
- Dec 2015 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- 7 Nov 2021 (actual)
- First posted
- 23 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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%<HbA1c≤10%) seeking implant placement in the mandible. We will collect intra-operative bone specimens at baseline and blood samples to assess bone structural alterations (H\&E stain), microvascular density (immunohistochemistry), bound RANKL/OPG (immunohistochemistry) and serum RANKL/OPG (ELISA). Implant integration and success will be assessed at 3, 6, 12 and 36-months.
Obtained results will give dental researchers new insights into the pathophysiology of the alveolar bone in diabetes and will provide information on the safety and efficacy of implant placement in type II diabetic patients that cannot control their glycemic status. Collectively, this work will pave the way for identifying efficacious implant treatment modalities for persons that live with type II diabetes to alleviate the morbidity associated with tooth loss in this susceptible population group.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Well-controlled diabetic (WC) | – | Device: Well-controlled diabetic (WC)well-controlled diabetic controls (HbA1c ≤ 7.0%), individuals will receive a single 4.1 Titanium-Zirconia, hydrophilic (Roxolid) implant placed in the posterior mandible, a bone core will be taken for histologic and histomorphometric analysis. |
| Poorly controlled diabetics (PC) | – | Device: Poorly controlled diabetics (PC)Poorly controlled diabetics (HbA1c >7.5% \& <10%), individuals will receive a single 4.1 Titanium-Zirconia, hydrophilic (Roxolid) implant placed in the posterior mandible, a bone core will be taken for histologic and histomorphometric analysis. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with diagnosed type II DM exhibiting at least one edentulous site in the posterior mandible or canine region presenting with levels of HbA1c >7.5% \& <10% for enrollment in the PC group and HbA1c ≤ 7.0% for enrollment in the WC group.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Well-controlled diabetic (WC)Each individual will receive one implant (4.1 Titanium-Zirconia, hydrophilic-Roxolid), that will be placed in the posterior mandible. | Device | Well-controlled diabetic (WC) |
| Poorly controlled diabetics (PC)Each individual will receive one implant (4.1 Titanium-Zirconia, hydrophilic-Roxolid), that will be placed in the posterior mandible. | Device | Poorly controlled diabetics (PC) |
Primary outcome
Differences in alveolar bone vascularity among well-controlled and not well-controlled diabetic patients.
Time frame: Baseline (intra-operative bone sample)
The difference between alveolar bone vascularity of well-controlled and not well-controlled diabetic patients by immunostaining
1 secondary outcome
RANK-L to OPG ratio
Time frame: Baseline to 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George Kotsakis, DDS principal investigator
University of Washington
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, run by University of Minnesota at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in alveolar bone vascularity among well-controlled and not well-controlled diabetic patients. (time frame: Baseline (intra-operative bone sample)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.