Kidney and Periodontal Disease Study (KAPD)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01802216
First received: February 15, 2013
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention
Chronic Kidney Disease
Periodontal Disease
Procedure: Scaling and root planing
Drug: Minocycline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Kidney and Periodontal Disease Study

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Number of participants completing study protocol [ Time Frame: conclusion of study (month 12) ] [ Designated as safety issue: No ]
    The investigators will determine the number of participants who complete baseline, month 4, month 8, and month 12 study visits.

  • serum creatinine [ Time Frame: baseline ] [ Designated as safety issue: No ]
    The investigators will measure serum creatinine as a traditional biomarker of kidney function.

  • change in serum creatinine [ Time Frame: baseline and study month 4 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum creatinine (a traditional biomarker of kidney function) from baseline to study month 4.

  • change in serum creatinine [ Time Frame: study month 4 and 12 ] [ Designated as safety issue: No ]
    The investigators will measure change serum creatinine (a traditional biomarker of kidney function) from study month 4 to 12.

  • albuminuria [ Time Frame: baseline ] [ Designated as safety issue: No ]
    The investigators will measure urine albumin to creatinine ratio as a marker of glomerular injury.

  • change in albuminuria [ Time Frame: baseline and study month 4 ] [ Designated as safety issue: No ]
    The investigators will measure change in urine albumin to creatinine ratio (a marker of glomerular injury) from baseline to study month 4.

  • change in albuminuria [ Time Frame: study month 4 and 12 ] [ Designated as safety issue: No ]
    The investigators will measure change in urine albumin to creatinine ratio (a marker of glomerular injury) from study month 4 to 12.

  • urine NGAL [ Time Frame: baseline ] [ Designated as safety issue: No ]
    The investigators will measure urine neutrophil gelatinase-associated lipocalin (NGAL) as a marker of tubular injury.

  • change in urine NGAL [ Time Frame: baseline and study month 4 ] [ Designated as safety issue: No ]
    The investigators will measure change in urine neutrophil gelatinase-associated lipocalin (NGAL) (a marker of tubular injury) from baseline to study month 4.

  • change in urine NGAL [ Time Frame: study month 4 and 12 ] [ Designated as safety issue: No ]
    The investigators will measure change in urine neutrophil gelatinase-associated lipocalin (NGAL) (a marker of tubular injury) from study month 4 to 12.

  • serum NGAL [ Time Frame: baseline ] [ Designated as safety issue: No ]
    The investigators will measure serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of tubular injury.

  • change in serum NGAL [ Time Frame: baseline and study month 4 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum neutrophil gelatinase-associated lipocalin (NGAL) (a marker of tubular injury) from baseline to study month 4.

  • change in serum NGAL [ Time Frame: study month 4 and 12 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum neutrophil gelatinase-associated lipocalin (NGAL) (a marker of tubular injury) from study month 4 to 12.

  • serum ADMA [ Time Frame: baseline ] [ Designated as safety issue: No ]
    The investigators will measure serum asymmetrical dimethylarginine (ADMA) as a marker of renal endothelial injury.

  • change in serum ADMA [ Time Frame: baseline and study month 4 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum asymmetrical dimethylarginine (ADMA) (a marker of renal endothelial injury) from baseline to study month 4.

  • change in serum ADMA [ Time Frame: study month 4 and 12 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum asymmetrical dimethylarginine (ADMA) (a marker of renal endothelial injury) from study month 4 to 12.


Secondary Outcome Measures:
  • serum IL-6 [ Time Frame: baseline ] [ Designated as safety issue: No ]
    The investigators will measure serum IL-6 as a biomarker of systemic inflammation.

  • change in serum IL-6 [ Time Frame: baseline and study month 4 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum IL-6 (a biomarker of systemic inflammation) from baseline to study month 4.

  • change in serum IL-6 [ Time Frame: study month 4 and 12 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum IL-6 (a biomarker of systemic inflammation) from study month 4 to 12.

  • serum hsCRP [ Time Frame: baseline ] [ Designated as safety issue: No ]
    The investigators will measure serum highly sensitive C-reactive protein (hsCRP) as a biomarker of systemic inflammation.

  • change in serum hsCRP [ Time Frame: baseline and study month 4 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum highly sensitive C-reactive protein (hsCRP) (a biomarker of systemic inflammation) from baseline to study month 4.

  • change in serum hsCRP [ Time Frame: study month 4 and 12 ] [ Designated as safety issue: No ]
    The investigators will measure change in serum highly sensitive C-reactive protein (hsCRP) (a biomarker of systemic inflammation) from study month 4 to 12.


Estimated Enrollment: 51
Study Start Date: February 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 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.
Active Comparator: 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.
Procedure: Scaling and root planing
Other Names:
  • Deep cleaning
  • Subgingival cleaning
Drug: Minocycline
Other Name: Arestin

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

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01802216

Locations
United States, California
San Francisco General Hospital
San Francisco, California, United States, 94110
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Vanessa Grubbs, MD, MPH University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01802216     History of Changes
Other Study ID Numbers: A119016
Study First Received: February 15, 2013
Last Updated: February 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
chronic kidney disease progression
periodontal disease
intensive periodontal disease treatment

Additional relevant MeSH terms:
Kidney Diseases
Periodontal Diseases
Renal Insufficiency, Chronic
Mouth Diseases
Renal Insufficiency
Stomatognathic Diseases
Urologic Diseases
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014