DMRCT: Impact of Periodontal Therapy on Patients With Diabetes

• Sponsor: State University of New York at Buffalo (Other)
• Overall Status: Completed
• CT.gov ID: NCT04830969
• Collaborator: Sunstar, Inc. (Industry)
• Enrollment: 104
• Location: 1
• Arms: 4
• Actual Duration (Months): 50.7
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

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:

1. Scaling and root planning (SRP) alone, or

2. 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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type II; Periodontitis	Drug: Chlorhexidine gluconate oral rinse; Procedure: Scaling & Root Planing; Device: Soft Picks	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Impact of Periodontal Therapy on Patients With Diabetes: A Pilot Study
• Actual Study Start Date: Nov 8, 2016
• Actual Primary Completion Date: Jan 28, 2021
• Actual Study Completion Date: Jan 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: Diabetic + SRP + SPT 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; 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.; Other Names: Paroex ; Procedure: Scaling & Root Planing; 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.; Other Names: SRP ; Device: Soft Picks; 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.
Experimental: B: Non-Diabetic + SRP + SPT 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; 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.; Other Names: Paroex ; Procedure: Scaling & Root Planing; 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.; Other Names: SRP ; Device: Soft Picks; 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.
Active Comparator: C: Diabetic + SRP The third group, C, includes diabetics with periodontal disease; they will receive standard therapy, scaling and root planing (SRP).	Procedure: Scaling & Root Planing; 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.; Other Names: SRP
Active Comparator: D: Non-Diabetic + SRP The second group, D, includes non-diabetics with periodontal disease; they will receive standard therapy, scaling and root planing (SRP).	Procedure: Scaling & Root Planing; 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.; Other Names: SRP

Outcome Measures

Primary Outcome Measures

1. Change in Probing pocket depth at the 6-month post-SRP completed at Baseline [Baseline to 6 months]

   Periodontal PD in millimeters is measured with a UNC-15 periodontal probe on 6 sites per tooth; site status is compared between timepoints measured

Secondary Outcome Measures

1. Changes in Bleeding on Probing at 3, 6, 9,12 months after treatment at Baseline [Baseline to 3 months; Baseline to 6 months; Baseline to 9 months; Baseline to 12 months]

   0 is the absence of gingival bleeding and 1 is the presence of gingival bleeding after probing and measuring for pocket depth.

2. Changes in Clinical attachment level at 3, 6, 9,12 months after treatment at Baseline [Baseline to 3 months; Baseline to 6 months; Baseline to 9 months; Baseline to 12 months]

   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.

3. Changes in Gingival Index at 3, 6, 9,12 months after treatment at Baseline [Baseline to 3 months; Baseline to 6 months; Baseline to 9 months; Baseline to 12 months]

   Gingival index is determined on 6 sites of all teeth present, except for the third molars. 0 is the absence of inflammation, 1 is the presence of inflammation (redness).

4. Change in Plaque Index at 3, 6, 9,12 months after treatment at Baseline [Baseline to 3 months; Baseline to 6 months; Baseline to 9 months; Baseline to 12 months]

   Plaque is visually measured on 6 sites per tooth; 0 is the absence of any plaque. 1 is the presence of plaque.

5. Change in Probing Pocket Depth at 3, 6, 9, and 12 months after treatment [Baseline to 3 months; Baseline to 6 months; Baseline to 9 months; Baseline to 12 months]

   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

6. Changes in Hemoglobin A1c at 3, 6, and 12 months after treatment [Baseline to 3 months; Baseline to 6 months; Baseline to 12 months]

   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.

7. Changes in Fasting blood glucose at 3, 6, and 12 months after treatment [Baseline to 3 months; Baseline to 6 months; Baseline to 12 months]

   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.

8. Change in insulin at 3, 6, and 12 months after treatment [Baseline to 3 months; Baseline to 6 months; Baseline to 12 months]

   Insulin is measured in a fasting state from a blood draw and indicates the body's baseline resistance or sensitivity to insulin. It is used to monitor the amount of insulin produced and identify insulin resistance. If the level is low (less than 2 mcUnit/mL) it means not enough insulin is being produced; if the level is high (more than 20 mcUnit/mL) it indicates diabetes and insulin resistance (or another metabolic disorder).

9. Change in high sensitivity C-reactive protein at 3, 6, and 12 months after treatment [Baseline to 3 months; Baseline to 6 months; Baseline to 12 months]

   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

10. Change in the subgingival plaque microbiome after periodontal treatment in group with SRP alone versus SRP + SPT. [Baseline to 3 months; Baseline to 6 months; Baseline to 12 months]

    Recent data indicate that the oral microbiome has essential functions in maintaining oral and systemic health. However, there is not much information available, and there are not many published reports investigating the benefits of periodontal therapy on the microbiome in diabetics. We think the microbiome influences clinical response to periodontal therapy and systemic changes showing improvement in diabetes status. We will examine the subgingival plaque microbiome in the four groups of participants. We will compare the different kinds and numbers of bacteria before and after the two treatments (SRP alone versus SRP+SPT (use of a mouthrinse and Soft Picks)) of periodontitis in diabetics and non-diabetics.

11. Change in the salivary microbiome after periodontal treatment in group with SRP alone versus SRP + SPT [Baseline to 3 months; Baseline to 6 months; Baseline to 12 months]

    Recent data indicate that the oral microbiome has essential functions in maintaining oral and systemic health. However, there is not much information available, and there are not many published reports investigating the benefits of periodontal therapy on the microbiome in diabetics. We think the microbiome influences clinical response to periodontal therapy and systemic changes showing improvement in diabetes status. We will examine the salivary microbiome in the four groups of participants. We will compare the different kinds and numbers of bacteria before and after the two treatments (SRP alone versus SRP+SPT (use of a mouthrinse and Soft Picks)) of periodontitis in diabetics and non-diabetics.

12. Change in the gut microbiome after periodontal treatment in group with SRP alone versus SRP + SPT [Baseline to 3 months; Baseline to 6 months; Baseline to 12 months]

    Recent data indicate that the oral microbiome has essential functions in maintaining oral and systemic health. In addition, there is not much information about how the gut (intestinal) microbiome influences general and oral health especially in periodontitis and diabetics. We think the gut microbiome may change after periodontal therapy is provided and after systemic changes showing improvement in diabetes status occur. We will examine the gut microbiome in the four groups of participants. We will compare the different kinds and numbers of bacteria before and after the two treatments of periodontitis (SRP alone versus SRP+SPT (use of a mouthrinse and Soft Picks)) in diabetics and non-diabetics.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Be able to understand the informed consent form and be willing and able to read and sign it.

2. At least 25 years of age.

3. Be able to understand and follow directions for study procedures.

4. At least 14 natural teeth, not counting third molars ("wisdom teeth").

5. At least 2 interproximal sites with CAL >= 4 mm or at least 2 interproximal sites with PD >= 5 mm.

Exclusion Criteria:

1. Presence of orthodontic appliances ("braces").

2. 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.

3. Abscess of the gingiva caused by periodontal disease, or visible gross tooth decay

4. A broken tooth root or an abscessed tooth. Subject may be allowed to participate in the study after the condition is successfully treated.

5. Periodontal treatment or antibiotic therapy in the past 6 months.

6. Have used cigarettes or other tobacco products in the past year.

7. Body mass index (BMI) is > 40.

8. Have regularly used non-steroidal anti-inflammatory drugs (such as >= 325 mg aspirin or ibuprofen) over the past 3 weeks.

9. Regularly using drugs that weaken the immune system (such as corticosteroids taken by mouth or injection, and cyclosporine).

10. Have participated in another clinical research study in the past 30 days.

11. Pregnant or breastfeeding.

12. Have a condition that we feel will make study participation unsafe or difficult for the patient.

13. Require premedication for dental exams.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University at Buffalo	Buffalo	New York	United States	14214

Sponsors and Collaborators

• State University of New York at Buffalo
• Sunstar, Inc.

Investigators

• Principal Investigator: Robert E Schifferle, DDS, PhD, University at Buffalo, State University of New York

Study Documents (Full-Text)

None provided.

More Information

Publications

• Abouassi T, Woelber JP, Holst K, Stampf S, Doerfer CE, Hellwig E, Ratka-Krüger P. Clinical efficacy and patients' acceptance of a rubber interdental bristle. A randomized controlled trial. Clin Oral Investig. 2014 Sep;18(7):1873-80. doi: 10.1007/s00784-013-1164-3. Epub 2014 Jan 10.
• Arora N, Papapanou PN, Rosenbaum M, Jacobs DR Jr, Desvarieux M, Demmer RT. Periodontal infection, impaired fasting glucose and impaired glucose tolerance: results from the Continuous National Health and Nutrition Examination Survey 2009-2010. J Clin Periodontol. 2014 Jul;41(7):643-52. doi: 10.1111/jcpe.12258. Epub 2014 May 25.
• Beiswanger BB, Mallat ME, Jackson RD, Mau MS, Farah CF, Bosma ML, Bollmer BW, Hancock EB. Clinical effects of a 0.12% chlorhexidine rinse as an adjunct to scaling and root planing. J Clin Dent. 1992;3(2):33-8.
• Borgnakke WS, Chapple IL, Genco RJ, Armitage G, Bartold PM, D'Aiuto F, Eke PI, Giannobile WV, Kocher T, Kornman KS, Lang NP, Madianos PN, Murakami S, Nishimura F, Offenbacher S, Preshaw PM, Rahman AU, Sanz M, Slots J, Tonetti MS, Van Dyke TE. The multi-center randomized controlled trial (RCT) published by the journal of the American Medical Association (JAMA) on the effect of periodontal therapy on glycated hemoglobin (HbA1c) has fundamental problems. J Evid Based Dent Pract. 2014 Sep;14(3):127-32. doi: 10.1016/j.jebdp.2014.04.017. Epub 2014 May 21.
• Colombo AP, Bennet S, Cotton SL, Goodson JM, Kent R, Haffajee AD, Socransky SS, Hasturk H, Van Dyke TE, Dewhirst FE, Paster BJ. Impact of periodontal therapy on the subgingival microbiota of severe periodontitis: comparison between good responders and individuals with refractory periodontitis using the human oral microbe identification microarray. J Periodontol. 2012 Oct;83(10):1279-87. Epub 2012 Feb 10.
• Colombo AP, Boches SK, Cotton SL, Goodson JM, Kent R, Haffajee AD, Socransky SS, Hasturk H, Van Dyke TE, Dewhirst F, Paster BJ. Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray. J Periodontol. 2009 Sep;80(9):1421-32. doi: 10.1902/jop.2009.090185.
• Engebretson S, Kocher T. Evidence that periodontal treatment improves diabetes outcomes: a systematic review and meta-analysis. J Periodontol. 2013 Apr;84(4 Suppl):S153-69. doi: 10.1902/jop.2013.1340017. Review.
• Engebretson SP, Hyman LG, Michalowicz BS, Schoenfeld ER, Gelato MC, Hou W, Seaquist ER, Reddy MS, Lewis CE, Oates TW, Tripathy D, Katancik JA, Orlander PR, Paquette DW, Hanson NQ, Tsai MY. The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial. JAMA. 2013 Dec 18;310(23):2523-32. doi: 10.1001/jama.2013.282431.
• Faveri M, Gursky LC, Feres M, Shibli JA, Salvador SL, de Figueiredo LC. Scaling and root planing and chlorhexidine mouthrinses in the treatment of chronic periodontitis: a randomized, placebo-controlled clinical trial. J Clin Periodontol. 2006 Nov;33(11):819-28. Epub 2006 Sep 11.
• Kirst ME, Li EC, Alfant B, Chi YY, Walker C, Magnusson I, Wang GP. Dysbiosis and alterations in predicted functions of the subgingival microbiome in chronic periodontitis. Appl Environ Microbiol. 2015 Jan;81(2):783-93. doi: 10.1128/AEM.02712-14. Epub 2014 Nov 14.
• Nelson RG, Shlossman M, Budding LM, Pettitt DJ, Saad MF, Genco RJ, Knowler WC. Periodontal disease and NIDDM in Pima Indians. Diabetes Care. 1990 Aug;13(8):836-40.
• Pérez-Chaparro PJ, Gonçalves C, Figueiredo LC, Faveri M, Lobão E, Tamashiro N, Duarte P, Feres M. Newly identified pathogens associated with periodontitis: a systematic review. J Dent Res. 2014 Sep;93(9):846-58. doi: 10.1177/0022034514542468. Epub 2014 Jul 29. Review.
• Santos VR, Lima JA, Miranda TS, Gonçalves TE, Figueiredo LC, Faveri M, Duarte PM. Full-mouth disinfection as a therapeutic protocol for type-2 diabetic subjects with chronic periodontitis: twelve-month clinical outcomes: a randomized controlled clinical trial. J Clin Periodontol. 2013 Feb;40(2):155-62. doi: 10.1111/jcpe.12040.
• Sgolastra F, Severino M, Pietropaoli D, Gatto R, Monaco A. Effectiveness of periodontal treatment to improve metabolic control in patients with chronic periodontitis and type 2 diabetes: a meta-analysis of randomized clinical trials. J Periodontol. 2013 Jul;84(7):958-73. doi: 10.1902/jop.2012.120377. Epub 2012 Oct 29. Review.
• Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M, Knowler WC, Pettitt DJ. Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years. J Periodontol. 1998 Jan;69(1):76-83.
• Wang J, Qi J, Zhao H, He S, Zhang Y, Wei S, Zhao F. Metagenomic sequencing reveals microbiota and its functional potential associated with periodontal disease. Sci Rep. 2013;3:1843. doi: 10.1038/srep01843.

• Responsible Party: Robert Schifferle, DDS, PhD, Principal Investigator, State University of New York at Buffalo
• ClinicalTrials.gov Identifier: NCT04830969
• Other Study ID Numbers: STUDY00000962
• First Posted: Apr 5, 2021
• Last Update Posted: Apr 19, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Periodontitis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Chlorhexidine; Chlorhexidine gluconate

Study Results

No Results Posted as of Apr 19, 2021