Chronic Kidney Disease, Periodontal Disease
Conditions
Keywords
chronic kidney disease progression, periodontal disease, intensive periodontal disease treatment
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: 1. To assess the feasibility of recruiting patients to this pilot trial. 2. 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.
Interventions
PROCEDUREScaling and root planing
non-surgical periodontal disease treatment
DRUGMinocycline
antibiotic microspheres
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 20-75 years 2. Speaks English or Spanish 3. At least two measurements of estimated glomerular filtration (eGFR) rate 15-59 ml/min/1.73m2 within the preceding 12 months 4. No eGFR increase by \>= 50% in the preceding 6 months 5. Moderate/severe periodontal disease in accordance with the Centers for Disease Control and Prevention/American Academy of Periodontology definition
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Completing Study Protocol | Baseline, Month 4, Month 8, Month 12 | The investigators will determine the number of participants who complete baseline, month 4, month 8, and month 12 study visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Estimated Glomerular Filtration Rate | Baseline, Month 4, Month 12 | 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 |
Participant flow
Recruitment details
This study enrolled English and Spanish-speaking patients 20-75 years old receiving primary care within the San Francisco Community Health Network. Patients with chronic kidney disease, not on dialysis, and moderate to severe periodontal disease are invited to participate.
Pre-assignment details
Participants are assigned in a 2:1 ratio to control or intensive treatment group, randomization is stratified by presence of diabetes. Enrollment began February 2014 until September 2016. 101 participants attended the in-person oral exam screening. 55 were randomized, 46 were excluded (41 did not meet periodontal disease criteria and 5 declined.
Participants by arm
| Arm | Count |
|---|---|
| Control/Delayed Treatment 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. | 17 |
| Intensive Periodontal Disease Treatment 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.
Scaling and root planing: non-surgical periodontal disease treatment
Minocycline: antibiotic microspheres | 34 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12 Month Visit | Participant did not show to visit | 3 | 4 |
| 4 Month Visit | Participant did not show to visit | 3 | 4 |
| 8 Month Visit | Participant did not show to visit | 3 | 5 |
Baseline characteristics
| Characteristic | Control/Delayed Treatment | Intensive Periodontal Disease Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 9 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 25 Participants | 40 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 19 Participants | 24 Participants |
| Race/Ethnicity, Customized Hispanic | 5 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Female | 4 Participants | 13 Participants | 17 Participants |
| Sex: Female, Male Male | 13 Participants | 21 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 34 |
| other Total, other adverse events | 0 / 17 | 0 / 34 |
| serious Total, serious adverse events | 0 / 17 | 1 / 34 |
Outcome results
Primary
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.
Time frame: Baseline, Month 4, Month 8, Month 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control/Delayed Treatment | Number of Participants Completing Study Protocol | Completed Baseline Visit | 17 Participants |
| Control/Delayed Treatment | Number of Participants Completing Study Protocol | Completed 4 Month Visit | 14 Participants |
| Control/Delayed Treatment | Number of Participants Completing Study Protocol | Completed 8 Month Visit | 14 Participants |
| Control/Delayed Treatment | Number of Participants Completing Study Protocol | Completed 12 Month Visit | 14 Participants |
| Intensive Periodontal Disease Treatment | Number of Participants Completing Study Protocol | Completed 12 Month Visit | 30 Participants |
| Intensive Periodontal Disease Treatment | Number of Participants Completing Study Protocol | Completed Baseline Visit | 34 Participants |
| Intensive Periodontal Disease Treatment | Number of Participants Completing Study Protocol | Completed 8 Month Visit | 29 Participants |
| Intensive Periodontal Disease Treatment | Number of Participants Completing Study Protocol | Completed 4 Month Visit | 30 Participants |
Secondary
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
Time frame: Baseline, Month 4, Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control/Delayed Treatment | Change in Estimated Glomerular Filtration Rate | Baseline Visit | 46.3 mL/min/1.73m^2 | Standard Deviation 10.8 |
| Control/Delayed Treatment | Change in Estimated Glomerular Filtration Rate | 4 Month Vist | 44.7 mL/min/1.73m^2 | Standard Deviation 12.1 |
| Control/Delayed Treatment | Change in Estimated Glomerular Filtration Rate | 12 month Visit | 45.6 mL/min/1.73m^2 | Standard Deviation 12.4 |
| Intensive Periodontal Disease Treatment | Change in Estimated Glomerular Filtration Rate | Baseline Visit | 43.4 mL/min/1.73m^2 | Standard Deviation 14.7 |
| Intensive Periodontal Disease Treatment | Change in Estimated Glomerular Filtration Rate | 4 Month Vist | 43.2 mL/min/1.73m^2 | Standard Deviation 16.6 |
| Intensive Periodontal Disease Treatment | Change in Estimated Glomerular Filtration Rate | 12 month Visit | 42.4 mL/min/1.73m^2 | Standard Deviation 18.3 |