Given the public health importance of increased P levels in the general population and specifically in patients with chronic kidney disease, it is of great importance to evaluate the ability of a medical food such as K2CG to reduce elevated serum P levels. In patients with CKD receiving dialysis it has been estimated that sustained control of serum P may result in an approximate 17% reduction in mortality.
The investigators have conducted a previous pilot double blind randomized controlled study of K2CG 20 mg and 40 mg BID for 4 weeks in 90 patients with ESRD. In this initial study the investigators did not observe a statistically significant reduction in either serum P or salivary P with active therapy as compared to placebo. However, a clear trend towards a reduction in serum P was seen in the randomized phase of the study with the active gum administered twice a day. During the open-label period where the gum was administered thrice-daily the investigators did see a statistically significant reduction in serum P of 0.3 mg/dL. Moreover, in patients with CKD not on dialysis, the investigators observed a reduction in mean serum P of approximately 0.2 mg/dL. While not statistically significant, this trial was not powered to detect this level of change in serum P and was underpowered to do so.. Differences in this range (0.2-0.4 mg/dL) have been reported in studies utilizing dietary manipulation (plant protein versus animal protein) and with the use of Niacin and are felt to be clinically meaningful reductions.
The investigators have previously also conducted a cross-sectional observational study evaluating salivary P levels across a wide spectrum of eGFR. The data indicate that mean salivary P is uniformly increased (15-25 mg/dL) relative to serum P (2.5- 4.5 mg/dL) being approximately 5-7X higher as shown below (group 1 = eGFR \> 90, group 7= eGFR \< 15). Importantly, salivary P was similar across the entire spectrum of eGFR.
The investigators have previously conducted a clinical trial evaluating several different formulations of K2CG with varying amounts of chitosan loading into the gum base, variable weights of gum base and 2 different formulations of gum base. In these trials the investigators further studied the effects of gum chewing in either the fasted or fed state and the effects of varying amounts of gum chewing time. Results from this study have demonstrated that the maximal amount of P loading into the K2CG is seen with the 1g chewing gum containing 20 mg chitosan and that the maximal effect is seen with 30 minutes of gum chewing.
Based on data from this study the investigators have chosen this strength/formulation for the primary efficacy endpoint assessment in the current protocol. Similar efficacy results with regard to total P loading per chewing gum were seen with the 2.0 gram, 60 mg chitosan chewing gum and there was an indication that subjects had a subjective preference for this formulation. As a result, this protocol will also assess (as a secondary efficacy endpoint) the reduction in serum P with this strength/formulation during an open label phase only in those subjects who have responded during the primary efficacy assessment phase. This will allow a comparison of efficacy between the 2 gum sizes/strengths among known 'responders' with regard to serum P reduction.
