Kidney and Periodontal Disease Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is (1) to determine whether a 12-month trial of patients from underserved communities with clinically significant gum disease and kidney disease randomly assigned to intensive gum disease treatment or delayed treatment is feasible and (2) to determine the variability of various tests of kidney function and inflammation in response to intensive gum disease treatment.

Detailed Description
-----------------
This is a randomized controlled pilot trial to two intention-to-treat treatment arms: intensive periodontal therapy or control-delayed periodontal therapy. The investigators' goals are to test the feasibility of conducting this trial among an underserved (mostly poor and low literacy) population and to determine the variability of renal and inflammatory biomarkers in response to intensive periodontal therapy over a 12 month period among participants with both chronic kidney disease (CKD) and significant periodontal disease. Randomization will be restricted with respect to diabetes (a strong risk factor for causing/aggravating both CKD and periodontal disease) to prevent an imbalance between the two arms. The investigators will recruit 51 patients from the San Francisco General Hospital (SFGH) Renal Clinic. Participants will be assigned 2:1 to the intervention group for the intensive periodontal treatment protocol (n=34) or to the control/delayed treatment group for rescue periodontal treatment only with intensive treatment at the end of the study (n=17). Hypothesis: A large scale randomized controlled trial of intensive periodontal treatment among the underserved will be feasible (with respect to enrollment, randomization, adherence and variability in clinical outcomes). Specific Aims: To assess the feasibility of recruiting patients to this pilot trial. To determine the variability of kidney biomarkers in response to periodontal disease treatment. Statistical Analysis: The investigators will calculate descriptive statistics (mean, standard deviation) of each clinical outcome which will include a traditional marker of kidney function (serum creatinine), markers of kidney structure [as glomerular injury (albuminuria) and tubular injury (neutrophil gelatinase-associated lipocalin (NGAL))]; a marker of vascular endothelial injury (asymmetrical dimethylarginine (ADMA)); and markers of systemic inflammation (IL-6 and C-reactive protein) measured at baseline, study month 4, and study month 12. The investigators will use repeated-measures generalized estimating equations (GEE) to compare changes in clinical outcomes over time within each treatment group and to compare differences between treatment groups taking individual change over time into account. Sample Size Calculation: This is a pilot study. To the investigators' knowledge, there are no existing data of the anticipated effect size of periodontal treatment to inform sample size calculations. However, because a primary aim is to determine the variability of various renal and inflammatory biomarkers, the investigators seek to enroll at least 30 subjects in the intervention arm of the trial.

Official Title
-----------------
Kidney and Periodontal Disease Study

Conditions
-----------------
Chronic Kidney Disease, Periodontal Disease

Intervention / Treatment
-----------------
* Procedure: Scaling and root planing
* Drug: Minocycline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 20-75 years Speaks English or Spanish At least two measurements of estimated glomerular filtration (eGFR) rate 15-59 ml/min/1.73m2 within the preceding 12 months No eGFR increase by >= 50% in the preceding 6 months Moderate/severe periodontal disease in accordance with the Centers for Disease Control and Prevention/American Academy of Periodontology definition Exclusion Criteria: General Exclusion Criteria. Subjects must NOT be: Under age 20 or over age 75 Unable to understand and provide informed consent Receiving current immunosuppressant therapy. Receiving current anticoagulation therapy resulting in an elevated prothrombin time or an International Normalized Ratio (INR) greater than 2.0 Pregnant. Oral Exclusion Criteria. Subjects must NOT: Have fewer than 6 natural teeth Requires antibiotic prophylaxis for dental procedures as defined by the 2007 American Heart Association guidelines (patients with prosthetic heart valves, those with prosthetic material used for cardiac valve repair, those who have had a history of infective endocarditis, or those with congenital heart defects repaired with prosthetic material). Have severe dental disease defined as deep dental caries, endodontic involvement of one or more teeth, presence of abscesses of periodontal or endodontic origin, or dental conditions requiring immediate treatment. Have any hard or soft tissue lesion requiring further evaluation and/or treatment. Have known allergy to minocycline, tetracyclines, or polyglycolide polymers.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control/Delayed Treatment<br>Baseline panoramic x-ray (Panorex) and complete oral examinations at every visit. Rescue scaling and root planing only to sites of periodontal disease progression (since prior examination) of greater than 3mm. Subjects will be informed of their assignment to the delayed treatment group and provided referral list of local dentists should patient not feel comfortable waiting until end of study for full intensive periodontal disease treatment. Written and verbal instruction in oral hygiene. Provision of oral hygiene supplies. | |
| Active Comparator: Intensive periodontal disease treatment<br>Baseline panoramic x-ray (Panorex) and complete oral examinations at every visit. Intensive periodontal disease treatment to include administration of local anesthetic to up to two quadrants for scaling and root planing with ultrasonic and hand instruments. Minocycline will be applied to any sites with probing depth >=5mm. Hopeless teeth in scaled quadrants will be extracted. Written and verbal instruction in oral hygiene. Provision of oral hygiene supplies. | Procedure: Scaling and root planing<br>* non-surgical periodontal disease treatment<br>* Other names: Subgingival cleaning;Drug: Minocycline<br>* antibiotic microspheres<br>* Other names: Arestin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Completing Study Protocol | The investigators will determine the number of participants who complete baseline, month 4, month 8, and month 12 study visits. | Baseline, Month 4, Month 8, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Estimated Glomerular Filtration Rate | Using the creatinine-based CKD-EPI equation, the investigators will determine change in estimated glomerular filtration rate from baseline to 12 month by individual and treatment group | Baseline, Month 4, Month 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chronic kidney disease progression, periodontal disease, intensive periodontal disease treatment