Impact of Periodontal Therapy on Patients With Diabetes

Study Overview
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Brief Summary
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With poorly controlled diabetes, periodontal status often worsens, and with severe periodontal conditions there is often poorer glycemic control. There are few published reports investigating the efficacy of periodontal therapy in diabetics and fewer that include evaluation of the oral microbial profiles (the microbiome). The investigators will examine systemic changes in diabetes status and microbiome influences on clinical response to periodontal therapy in a randomized clinical trial of participants with and without diabetes and with periodontal disease. Two different treatments will be used: Scaling and root planning (SRP) alone, or SRP and supportive periodontal therapy (SPT), the use of chlorhexidine gluconate rinse (Paroex®) and a rubber interdental bristle cleaner (Soft-Picks) The main goal of this clinical trial is to evaluate the effects of SRP alone versus SRP+SPT on clinical, microbiological and immunological status in participants. A clearer understanding of how periodontal therapy affects diabetes status could lead to the development of new therapies for periodontal disease and diabetes.

Detailed Description
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With poorly controlled diabetes, periodontal disease worsens, and with severe periodontal conditions, there is often poorer glycemic control. Published papers conclude that periodontal treatment leads to a reduction in hemoglobin A1c; however, other studies show limited or no improvement. Some patients do not respond well to professional periodontal therapy, even without diabetes, which could be related to poor oral hygiene and/or host factors including microbial profiles. There are few published papers investigating the efficacy of periodontal therapy in diabetics and fewer that include assessment of the oral microbiome. The investigators will examine systemic changes in diabetes status and microbiome influences on clinical response to periodontal therapy in a randomized clinical trial. It has been shown that chlorhexidine gluconate rinse leads to significant clinical improvement over standard periodontal therapy alone, and interdental tooth cleaners remove more dental plaque (leading to reduced gingival inflammation) effectively than brushing alone. Therefore, in this study, standard periodontal therapy, scaling and root planning (SRP) will be provided alone, or SRP plus supportive periodontal therapy (SPT), the use of chlorhexidine gluconate rinse (Paroex®) and a rubber interdental bristle cleaner (Soft-Picks), to diabetics and non-diabetics with periodontal disease to determine the differences in response between the groups. The main aim of this study is to evaluate the effects of SRP alone versus SRP+SPT on clinical, microbiological and immunological status of subjects with and without type 2 diabetes and with periodontal disease. A clearer understanding of how periodontal therapy affects diabetes status could lead to the development of novel new targeted therapies of both periodontal disease and diabetes.

Official Title
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Impact of Periodontal Therapy on Patients With Diabetes: A Pilot Study

Conditions
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Diabetes Mellitus, Type II, Periodontitis

Intervention / Treatment
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* Drug: Chlorhexidine gluconate oral rinse
* Procedure: Scaling & Root Planing
* Device: Soft Picks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able to understand the informed consent form and be willing and able to read and sign it. At least 25 years of age. Be able to understand and follow directions for study procedures. At least 14 natural teeth, not counting third molars (wisdom teeth). At least 2 interproximal sites with CAL >= 4 mm or at least 2 interproximal sites with PD >= 5 mm. Exclusion Criteria: Presence of orthodontic appliances (braces). An abnormal condition of lips, lining of the mouth, tongue, or gums (except for periodontal disease). If subject has a cold sore, canker sore, or injury in their mouth, they may return after the sore or injury heals. Abscess of the gingiva caused by periodontal disease, or visible gross tooth decay A broken tooth root or an abscessed tooth. Subject may be allowed to participate in the study after the condition is successfully treated. Periodontal treatment or antibiotic therapy in the past 6 months. Have used cigarettes or other tobacco products in the past year. Body mass index (BMI) is > 40. Have regularly used non-steroidal anti-inflammatory drugs (such as >= 325 mg aspirin or ibuprofen) over the past 3 weeks. Regularly using drugs that weaken the immune system (such as corticosteroids taken by mouth or injection, and cyclosporine). Have participated in another clinical research study in the past 30 days. Pregnant or breastfeeding. Have a condition that we feel will make study participation unsafe or difficult for the patient. Require premedication for dental exams.

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Diabetic + SRP + SPT<br>The first group, A, includes diabetics with periodontal disease; they will receive standard therapy, scaling & root planing plus supportive periodontal therapy (SPT) chlorhexidine gluconate (Paroex®) mouthrinse + Soft-Picks. | Drug: Chlorhexidine gluconate oral rinse<br>* Paroex® is a non-alcohol chlorhexidine preparation. Participants are to use 15 mL morning and evening for 3 months. With use of chlorhexidine, there is risk of reversible staining of teeth and the possibility of some alteration in taste. There is increased likeliness of staining in smokers, coffee drinkers and those who are susceptible to teeth staining in general. The cleaning of the front teeth is provided at the 3-month visit and helps to reduce any staining that may occur. If there is any alteration in taste, it should go away when use of chlorhexidine stops.<br>* Other names: Paroex;Procedure: Scaling & Root Planing<br>* SRP is standard treatment of periodontitis. It involves using a scaler to remover subgingival plaque and other debris in the space between teeth and gums.<br>* Other names: SRP;Device: Soft Picks<br>* Soft Picks are a rubber interdental bristle cleaner. Participants are to use Soft Picks morning and evening for all 12 months of the study. They may cause some bleeding of the gums at first usage, but the bleeding should lessen and stop as use is continued (as gums heal). Soft-Picks are a readily available consumer product sold in supermarkets and drug stores.<br>|
| Experimental: B: Non-Diabetic + SRP + SPT<br>The second group, B, includes non-diabetics with periodontal disease; they will receive standard therapy, scaling & root planing plus supportive periodontal therapy (SPT) chlorhexidine gluconate (Paroex®) mouthrinse + Soft-Picks. | Drug: Chlorhexidine gluconate oral rinse<br>* Paroex® is a non-alcohol chlorhexidine preparation. Participants are to use 15 mL morning and evening for 3 months. With use of chlorhexidine, there is risk of reversible staining of teeth and the possibility of some alteration in taste. There is increased likeliness of staining in smokers, coffee drinkers and those who are susceptible to teeth staining in general. The cleaning of the front teeth is provided at the 3-month visit and helps to reduce any staining that may occur. If there is any alteration in taste, it should go away when use of chlorhexidine stops.<br>* Other names: Paroex;Procedure: Scaling & Root Planing<br>* SRP is standard treatment of periodontitis. It involves using a scaler to remover subgingival plaque and other debris in the space between teeth and gums.<br>* Other names: SRP;Device: Soft Picks<br>* Soft Picks are a rubber interdental bristle cleaner. Participants are to use Soft Picks morning and evening for all 12 months of the study. They may cause some bleeding of the gums at first usage, but the bleeding should lessen and stop as use is continued (as gums heal). Soft-Picks are a readily available consumer product sold in supermarkets and drug stores.<br>|
| Active Comparator: C: Diabetic + SRP<br>The third group, C, includes diabetics with periodontal disease; they will receive standard therapy, scaling and root planing (SRP). | Procedure: Scaling & Root Planing<br>* SRP is standard treatment of periodontitis. It involves using a scaler to remover subgingival plaque and other debris in the space between teeth and gums.<br>* Other names: SRP;|
| Active Comparator: D: Non-Diabetic + SRP<br>The second group, D, includes non-diabetics with periodontal disease; they will receive standard therapy, scaling and root planing (SRP). | Procedure: Scaling & Root Planing<br>* SRP is standard treatment of periodontitis. It involves using a scaler to remover subgingival plaque and other debris in the space between teeth and gums.<br>* Other names: SRP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Probing Pocket Depth at the 6-month Post-SRP Completed at Baseline | Periodontal PD in millimeters is measured with a UNC-15 periodontal probe on 6 sites per tooth; site status is compared between timepoints measured | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Probing Pocket Depth at the 3-month Post-SRP Completed at Baseline | Periodontal PD in millimeters is measured with a UNC-15 periodontal probe on 6 sites per tooth; site status is compared between timepoints measured | Baseline to 3 months | 
| Changes in Clinical Attachment Level at 3, 6 Months After Treatment at Baseline | The distance from the Cemento-enamel Junction (CEJ) to the free gingival margin is measured with a periodontal probe. Millimeters of recession (loss of attachment) is recorded as a negative number; when the gingival margin is above the CEJ, the measurement (in millimeters) is recorded as positive. | Baseline to 3 months;Baseline to 6 months | 
| Change in % Sites With Probing Pocket Depth >= 4 mm of a Participant at the 3, 6 Months Post-SRP Completed at Baseline | The analysis is based on the measures of each participant. Participant instead of site is used as unite for arm/group. The measure, % sites with probing pocket depth >= 4 mm within each participant, indicates the portion of deep pocket in a participant. Periodontal PD in millimeters is measured with a UNC-15 periodontal probe on 6 sites per tooth; The percentage of sites with Periodontal PD >= 4 mm within each participant was compared between measured time points. | Baseline to 3 months; Baseline to 6 months | 
| Changes in Bleeding on Probing (BOP) Index of a Participant at 3, 6 Months After Treatment at Baseline | The analysis is based on the measures of each participant. 0 is the absence of gingival bleeding and 1 is the presence of gingival bleeding after probing and measuring for pocket depth. Bleeding on probing index is defined as the percentage of sites with presence of gingival bleeding after probing per participant. The value of bleeding on probing index ranges from 0 to 100 for each participant. The bleeding on probing index per participant is compared between time points measured. | Baseline to 3 months; Baseline to 6 months | 
| Change in Plaque Index of a Participant at 3, 6 Months After Treatment at Baseline | The analysis is based on the measures of each participant. Plaque is visually measured on 6 sites per tooth; 0 is the absence of any plaque. 1 is the presence of plaque. For each participant, 6 sites per tooth are evaluated. The Plaque Index (PI) of each participant is defined as the percentage of sites with plaque. The value of PI ranges from 0 to 100 for each participant. The PI of each participant is assessed and compared between measured time points. | Baseline to 3 months; Baseline to 6 months | 
| Change in Probing Pocket Depth at 3, 6 Months After Treatment in Diabetics and Non-diabetics | Probing depth (PD) or probing pocket depth (PPD), measured on six surfaces/tooth, is the distance in millimeters (mm) from the gingival margin to the base of the gingival pocket | Baseline to 3 months; Baseline to 6 months | 
| Changes in Clinical Attachment Level at 3, 6 Months After Treatment at Baseline in Diabetics and Non-diabetics | The distance from the Cemento-enamel Junction (CEJ) to the free gingival margin is measured with a periodontal probe. Millimeters of recession (loss of attachment) is recorded as a negative number; when the gingival margin is above the CEJ, the measurement (in millimeters) is recorded as positive. | Baseline to 3 months; Baseline to 6 months | 
| Change in % Sites With Probing Pocket Depth >= 4 mm of a Participant at the 3, 6 Months Post-SRP Completed at Baseline in Diabetics and Non-diabetics | The analysis is based on the measure of each participant. Periodontal PD in millimeters is measured with a UNC-15 periodontal probe on 6 sites per tooth; The percentage of sites with Periodontal PD >= 4 mm per participant is compared between measured time points. | Baseline to 3 months; Baseline to 6 months | 
| Changes in Bleeding on Probing (BOP) Index of a Participant at 3, 6 Months After Treatment at Baseline in Diabetics and Non-diabetics | The analysis is based on the measures of each participant. 0 is the absence of gingival bleeding and 1 is the presence of gingival bleeding after probing and measuring for pocket depth. Bleeding on probing index is defined as the percentage of sites with presence of gingival bleeding after probing per participant. The value of bleeding on probing index ranges from 0 to 100 for each participant. The bleeding on probing index per participant is compared between time points measured. | Baseline to 3 months; Baseline to 6 months | 
| Change in Plaque Index of a Participant at 3, 6 Months After Treatment at Baseline in Diabetics and Non-diabetics | The analysis is based on the measures of each participant. Plaque is visually measured on 6 sites per tooth; 0 is the absence of any plaque. 1 is the presence of plaque. For each participant, 6 sites per tooth are evaluated. The Plaque Index (PI) of each participant is defined as the percentage of sites with plaque. The value of PI ranges from 0 to 100 for each participant. The PI of each participant is assessed and compared between measured time points. | Baseline to 3 months; Baseline to 6 months | 
| Changes in Hemoglobin A1c at 6 Months After Treatment | Hemoglobin in A1c (HbA1c) tells the average level of blood sugar over the prior 2 to 3 months. Normal level is below 5.7%; 5.7%-6.4% indicates prediabetes; greater than 6.5% is indicative of diabetes. | Baseline to 6 months | 
| Changes in Fasting Blood Glucose at 6 Months After Treatment | Fasting blood sugar/glucose (FBS/FBG) is tested with a blood sample taken after an overnight fast. A fasting blood sugar level less than 100 mg/dL is normal; a fasting blood sugar level from 100 to 125 mg/dL is considered prediabetes; a level 126 mg/dL (7 mmol/L) or higher on two separate tests, indicates diabetes. | Baseline to 6 months | 
| Change in High Sensitivity C-reactive Protein at 6 Months After Treatment | The high-sensitivity C-reactive protein (hs-CRP) blood test measures body inflammation indicating infection or a chronic inflammatory disease such as periodontitis or diabetes. It also can be used to evaluate risk of developing coronary artery disease. A normal reading is less than 10 milligram per liter (mg/L); a level greater than 10 mg/L is a sign of serious infection, trauma or chronic disease likely requiring further testing to determine cause | Baseline to 6 months | 
| Changes in Hemoglobin A1c at 6 Months After Treatment in Diabetics and Non-diabetics | Hemoglobin in A1c (HbA1c) tells the average level of blood sugar over the prior 2 to 3 months. Normal level is below 5.7%; 5.7%-6.4% indicates prediabetes; greater than 6.5% is indicative of diabetes. | Baseline to 6 months | 
| Changes in Fasting Blood Glucose at 6 Months After Treatment in Diabetics and Non-diabetics | Fasting blood sugar/glucose (FBS/FBG) is tested with a blood sample taken after an overnight fast. A fasting blood sugar level less than 100 mg/dL is normal; a fasting blood sugar level from 100 to 125 mg/dL is considered prediabetes; a level 126 mg/dL (7 mmol/L) or higher on two separate tests, indicates diabetes. | Baseline to 6 months | 
| Change in High Sensitivity C-reactive Protein at 6 Months After Treatment in Diabetics and Non-diabetics | The high-sensitivity C-reactive protein (hs-CRP) blood test measures body inflammation indicating infection or a chronic inflammatory disease such as periodontitis or diabetes. It also can be used to evaluate risk of developing coronary artery disease. A normal reading is less than 10 milligram per liter (mg/L); a level greater than 10 mg/L is a sign of serious infection, trauma or chronic disease likely requiring further testing to determine cause | Baseline to 6 months | 
| Shannon Index of the Subgingival Plaque Microbiome at Baseline and 6 Months | Shannon index represents mean species diversity in a site at a local scale. Shannon index quantifies the uncertainty in predicting the species identity of an individual that is taken at random from the dataset. The minimum value is 0 and there is no maximum value. High values mean high species diversities. | Baseline; 6 Months | 
| Change in Distance to the Healthy Plane Based on the Subgingival Plaque Microbiome at 6 Months | Analysis of microbiome community changes using the healthy plane (HP) as a reference. A healthy plane was calculated by fitting a plane that minimizes the sum of squares of distances from HC samples to the nearest point on the plane. The distance of each sample to the HP was then calculated. Higher values of distance to HP mean microbiome community changes towards disease status | Baseline to 6 Months |