Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04020458 |
| Other study ID # |
1295706 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 9, 2018 |
| Est. completion date |
January 4, 2022 |
Study information
| Verified date |
July 2023 |
| Source |
Augusta University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The study aims to understand why dental infections in end-stage kidney patients results in
poor outcomes for kidney functions and eventually transplant. Further, if an active dental
treatment is provided to such patients, does it helps improve the kidney functional
parameters, and eventually results in better survival of kidney transplant. In addition, the
molecular markers that result in altered interactions between the blood cells and bacteria in
these patients will be identified and compared with those found in a healthy subjects, or
subjects with gum disease but no kidney disease. Besides, if any of the makers of altered
interactions found in the blood can be found to be altered in the saliva samples from the
patients with gum disease (periodontitis), and kidney disease, it will help to develop a
non-invasive oral risk test for predicting outcomes of kidney transplant survival.
Description:
PURPOSE: The Dental College of Georgia (DCG) and the Periodontics and Oral Health and
Diagnostic Sciences departments propose to develop a collaborative clinical and research
program with the Carlos and Marguerite Mason Trust Solid Organ Transplant Center at the
Augusta University (AU) Medical Center. The overall goal is to develop a dental intervention
program, with a research component, to address the role of dental infections in kidney
transplantation outcomes, with the goal of improving best practices for kidney transplant
patients. The study, which has been funded by the Mason Trust (C.W. Cutler, PI) is aimed
toward improving overall quality of life of the patients on dialysis or with kidney
transplant and reducing transplantation complications and failure rates.
AIM 1: To evaluate the effect of dental intervention on kidney transplant outcomes for
patients with chronic kidney diseases awaiting kidney transplant/ or having received a kidney
transplant within two (2) years. This aim will examine whether dental intervention will
improve outcomes of patients with periodontitis (PD) and kidney disease, including kidney
function and allograft survival in patients with chronic kidney diseases
post-transplantation. Hypothesis is that active dental intervention will result in better
oral health in patients with chronic kidney diseases resulting in better transplantation
outcomes.
AIM 2: To determine the pathophysiological links between PD and chronic kidney disease with
or without kidney transplantation.
Hypothesis is that active treatment of PD in chronic kidney patients will shift the systemic
molecular profile towards anti-inflammatory, resulting in better transplant outcomes for
these patients. The correlation of expression of various molecular proteins in saliva and
blood will help to develop a non-invasive oral risk test for predicting outcomes of kidney
transplant survival.
There will be three groups in the study:
Control groups: There will be 2 control groups. The data from these two groups will help
establish the baseline for the different parameters to study in the experimental population.
1. Group 1: moderate to severe generalized periodontitis (PD) (no kidney disease).
2. Group 2: healthy controls, no PD or kidney disease.
Experimental group:
3) Group 3: Patients with chronic kidney disease : i. Group 3a- stage 5 (without dialysis,
glomerular filtration rate (GFR) < 20)/ stage 5D (on dialysis), awaiting kidney transplant.
(n=50) ii. Group 3b- Stages 2-4 (patients who have had either a living donor transplant
(n=25), or deceased donor transplant within the last 2 years (n=25), with /without no history
of rejection of kidney transplant) (total n=50).
The Group 1 and Group 2 subjects will be recruited from the patient population at AU-Dental
College of Georgia (DCG), post-graduate periodontics clinic and/or primary care clinics at
AU-Medical College of Georgia or volunteers who are willing to participate in this research
study, after looking at study advertisements placed on DCG monitors or AU clinics. The group
3 patients will be recruited from among the patients registered at the AU Heath Kidney
Transplant Center, who are either awaiting kidney transplant (Group 3a) or have received
kidney transplant within last 2 years (Group 3b). The medical records of the potential will
be reviewed against pre-screening criteria to determine their eligibility for the study. The
eligible subjects will be invited for participating in the study.
At the pre-screening visit (visit 1), potential subjects will receive the Informed Consent
Document (ICD) describing the overall aim of the study, study design, participation, and
eligibility criteria. The consent process will occur in a separate room with no time
restrictions. All questions and concerns will be clarified by the PI /Periodontics residents
on the study or research coordinator. Consenting subjects will sign and date the consent
form, and will receive a copy of the ICD. Any study procedure will be initiated only after
obtaining a written, signed consent document from the potential subject. The consent document
will be stored in a locked drawer in the research coordinators office at the Clinical
Research Center, along with the subjects' records. At each of the subsequent visits (visits
2-8), eligible subjects will confirm consent to participate in the study.
Study procedures considered standard of care for all subjects:
1. Filling out a medical and dental history form
2. Being clinically examined by a dentist
3. Receiving oral hygiene instructions, oral health counseling, and referral for dental
treatment
4. Dental intervention plan for Group 1 and 3 subjects with periodontitis only, considered
standard of care i. Full mouth intraoral X-rays (FMX)
ii. Full periodontal exam, diagnosis, Oral hygiene instructions (OHI)
iii. RX: 7 days of p.o. metronidazole (250mg)/amoxicillin (500mg) T.I.D., combined with local
chlorhexidine rinses (not for subjects with Kidney transplant).
iv. Single visit intensive scaling and root planning (SRP) (full mouth)
v. Re-evaluation after 4-6 weeks (referral for definitive treatment)
vi. Extraction of teeth deemed hopeless based on periodontal, endodontic or restorative
considerations
vii. Caries control, sedative dressing (palliative), referral to endodontic dentist for root
canal treatment (RCT)
Assessment of kidney function parameters, such as creatinine level and glomerular filtration
rate, will be done at the AU Health Kidney Transplant Center for Group 3 subjects, as part of
standard of care and follow-up visits at the clinic.
Study procedures for research purposes only on all subjects:
1. Phlebotomy for peripheral blood samples (15 mls per visit)
2. Sampling of dental plaque for microbiological analysis before and after dental
intervention program (DIP)
3. Measurement of unstimulated and stimulated salivary flow rate measurement and
4. Collection of whole saliva for microbiological analysis, cytokine profile and other
molecular markers.
Potential risks to subjects include
1. There is a small risk that subjects using antibiotics may have gastrointestinal
problems.
2. There is a small risk that the use of mouth rinses can temporarily stain teeth light
brown.
3. There is a small risk that the collection of a blood sample may cause major pain and
bruising where the needle enters the skin, fainting and/or infection
4. There is a very small risk that periodontal probing, subgingival plaque sample
collection, and dental anesthesia injections will cause major discomfort
5. There is a small risk that SRP may also cause major discomfort and pain
6. Withdrawal of fifteen (15) ml of blood from Group 3 subjects might put them at risk for
anemia. Group 3 patients will be monitored at the AU-Health Kidney Transplant Clinic for
anemia using CBC, hemoglobin and hematocrit levels.
Participants will be actively assessed for the occurrence of serious (SAEs) and non-serious
adverse events (NSAEs) throughout the study. SAEs are defined as fatal or life-threatening
events that require inpatient hospitalization or cause persistent or significant disability
or incapacity. NSAEs are defined as any unfavorable and unintended sign, symptom, condition
or disease temporally associated with a study intervention or medication. SAEs should be a
rare occurrence and NSAEs are likely related but not restricted to procedures for biological
sampling, scaling and root planning and antibiotic use including: inter-current illness,
fever, nausea, vomiting, diarrhea, rashes, drug interactions, drug hypersensitivity, gingival
pain, dentine hypersensitivity. Participants will be asked about any abnormal signs and
symptoms and intra-oral examinations will be performed at every dental visit. Moreover, a
phone number will be provided to participants for reporting any unexpected AE. Any
occurrences will be recorded in preset forms and the following items will be assessed:
description of the adverse event, period, frequency, severity, relationship with study
procedures and medications, action taken and resolution. All SAEs will be reported to the IRB
accordingly.
Confidentiality will be maintained by restricting access to subjects' data and
de-identification of datasets and specimens. De-identification of the research records will
be achieved by generating a subject study number. A separate list matching the subjects'
study numbers and dental records will be kept in a separate file, which will be stored in a
looked drawer in the research coordinator's office at the Clinical Research Center. Research
team members will only have access to confidential data as needed for the strict execution of
their functions. Subjects will not be identified by name in any report or publications
resulting from this study.
For the purpose of statistical analysis, there will be 4 groups with experimental group 3a
and 3b treated as separate groups.
As a preliminary step, the Shapiro-Wilk test will be used to assess normality of each
dependent variable (DV). If the DV appears to be normally distributed, four-group repeated
measures analysis based on a mixed effects regression model (MRM) will be performed. For each
DV, MRMs will be used to assess the significance of each of the following design factors and
covariates: (1) Within-subjects (repeated-measures) Factor: Time (6 levels: Baseline, 4
weeks, 3 months, 6 months, 1 year, 5 years); (2) Between-subjects Factor: Group (4 levels:
Groups 1, 2, 3a, 3b); (3) Interaction terms: Time by Group, Group by selected covariates,
Time by selected covariates; and (4) Covariates (age, race, sex, etc.). For each DV, several
competing covariance structures for the repeated measures will be examined, including
unstructured, compound symmetry, Huynh-Feldt, first-order autoregressive, first-order
autoregressive with heterogeneous variances, etc. The Akaike (AIC) and Bayesian (BIC)
Information Criteria will be used to select the most appropriate covariance structure.
Tukey-Kramer adjustments will be made to any post-hoc multiple comparisons in order to
control the family-wise error rate at the 0.05 level. If a DV appears to be non-normally
distributed, an attempt will be made to identify a transformation to normality using the
Box-Cox method. If an appropriate transformation cannot be found, robust multivariate
analyses will be used instead of standard normal-theory based methods. All statistical
analyses will be carried out using SAS 9.4, and all statistical tests will be performed using
a two-tailed significance level of 0.05 unless otherwise specified.
