Novel PAradigm to improve Inflammatory burden in end stage Renal disease (rePAIR): study protocol for a randomized controlled trial

Abstract

Background: Given the importance of inflammation as a predictor of poor outcomes in End Stage Renal Disease (ESRD), reductions in inflammatory biomarkers have been proposed as a critical target in this population. This study targets chronic periodontitis, an oral inflammatory disease of microbial etiology causing persistent inflammation in ESRD. Unlike the previously reported episodic periodontal interventions, we propose to control periodontal inflammation with a continuous maintenance and oral health behavior modifications. We hypothesize that this strategy will improve systemic inflammation and oxidative stress, oral health and quality of life within the 6-month observation period.

Methods: The rePAIR (novel PAradigm to improve Inflammatory burden in ESRD) study is a pilot and feasibility, parallel-arm, and randomized controlled clinical trial that will recruit 72 ESRD subjects with periodontitis in a model of computerized block randomization. This trial aims to compare the effect of standard-of-care vs. repeated non-surgical periodontal therapy on systemic and oral inflammatory burden. This trial will recruit ESRD adult patients with periodontitis older than 21 years old with a minimum of 12 teeth and no history of periodontal treatment within a year. The trial will examine serum C-reactive protein (CRP) (primary outcome) as a biomarker of inflammation as well as interleukin-6 (IL-6), F2 isofurans and F2 isoprostanes (secondary outcomes) and compare their difference between groups from baseline to 6 months. The trial will also compare the difference between groups in patient-centered and clinical oral outcomes from baseline to 6 months.

Discussion: The trial follows a rigorous and transparent study design capturing elements such as pre-specified eligibility criteria, pre-specified primary and secondary outcomes, detailed intervention description to allow replication, intervention random allocation and concealment, blinding in outcome assessment, appropriate sample size calculations, explanation of interim analysis, as per CONSORT Guidelines. Further, gender diversity is secured not only at recruitment but also throughout the trial and during the analysis. Therefore, treatment response outcomes will be examined per gender category. In order to manage anticipated problems, the protocol has included alternative approaches.

Trial registration: ClinicalTrials.gov, NCT03241511 . Registered on 7 August 2017.

Conflict of interest statement

Ethics approval and consent to participate

The study is conducted in accordance with the Declaration of Helsinki. The study received full board status review and approval by IRB Panel 1 including members: Karen Beyard PhD, Kai Chen MD PhD, Linda Choquette MSHC CCRP, Pamela Colwell BS, Alan Curto JD, Terese Donovan MS RN, Julian Ford PhD, William Kleinman JD, Kourosh Parham MD PhD, David Pendrys DDS PhD, Deborah Redford-Badwal DDS PhD, Melinda Sanders MD, Mitchell Sauerhoff PhD, Meryem Tuncel MD, Jeffrey Wasser MD, Catherine Wilcox M. Div, Andrew Winokur MD PhD. The study received approval by the UCONN Health Institutional Review Board (Approval number #16–111-1). The potential participants are enrolled after reviewing and signing the IRB approved informed consent.

Competing interests

RT, VBN, RC, MC, JB, EI declare no competing interest.

GF holds shares at the American Renal Associates.

JH serves as a consultant for Corvidia, Inc.

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Figures

Fig. 1

Standard protocol time points and items based on the SPIRIT guidelines. *Recommended content can be displayed using various schematic formats. See SPIRIT 2013 Explanation and Elaboration for examples from protocols. **List specific timepoints in this row

Fig. 2

Study Flow Chart