Clinical trial NCT01802216: Kidney and Periodontal Disease Study
Official title: Kidney and Periodontal Disease Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Periodontal Disease
Keywords: chronic kidney disease progression
periodontal disease
intensive periodontal disease treatment
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2013-03-01
Enrollment: 51
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: 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.

Eligibility criteria: 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 Exclusion Criteria. Subjects must NOT be:

1. Under age 20 or over age 75
2. Unable to understand and provide informed consent
3. Receiving current immunosuppressant therapy.
4. Receiving current anticoagulation therapy resulting in an elevated prothrombin time or an International Normalized Ratio (INR) greater than 2.0
5. Pregnant.

Oral Exclusion Criteria. Subjects must NOT:

1. Have fewer than 6 natural teeth
2. 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).
3. 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.
4. Have any hard or soft tissue lesion requiring further evaluation and/or treatment.
5. Have known allergy to minocycline, tetracyclines, or polyglycolide polymers.

Primary outcomes:
measure: Number of Participants Completing Study Protocol
timeFrame: Baseline, Month 4, Month 8, Month 12
Secondary outcomes:
measure: Change in Estimated Glomerular Filtration Rate
timeFrame: Baseline, Month 4, Month 12
Other outcomes:
Locations:
Study officials:
affiliation: University of California, San Francisco
name: Vanessa Grubbs, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grubbs V, Garcia F, Vittinghoff E, Jue BL, Ryder M, Lovett DH, Offenbacher S, Taylor G, Ganz P, Bibbins-Domingo K, Powe NR. Nonsurgical Periodontal Therapy in CKD: Findings of the Kidney and Periodontal Disease (KAPD) Pilot Randomized Controlled Trial. Kidney Med. 2019 Dec 2;2(1):49-58. doi: 10.1016/j.xkme.2019.09.005. eCollection 2020 Jan-Feb.