Release of substance P during peritoneal dialysis: effects of intervention. Controlled cross-over study of the neurokinin-1 receptor antagonist Aprepitant

INTERVENTION: Trade Name: Emend Product Name: Emend Product Code: EMEA/H/C/000527 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Emend Other descriptive name: APREPITANT Concentration unit: mg milligram(s) Concentration type: range Concentration number: 80‐125 Trade Name: TrioBe Product Name: TrioBe Pharmaceutical Form: Tablet Other descriptive name: FOLIC ACID Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.8‐ INN or Proposed INN: PYRIDOXINE HYDROCHLORIDE CAS Number: 58‐56‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 3‐ Other descriptive name: CYANOCOBALAMIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.5‐ CONDITION: End stage renal disease under treatment with peritoneal dialysis Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] ‐ Therapeutic techniques [E02] PRIMARY OUTCOME: Main Objective: In an earlier study in rats we demonstrated that experimental peritoneal dialysis (PD) induced a neurogenic inflammatory response in the peritoneum, leading to the release of neuropeptides substance P (SP) and CGRP.; By blocking the effects of SP (NK1 receptor blockade) we were able to reduce plasma protein loss (leakage of albumin from blood to the peritoneal cavity) by half.; Our primary hypothesis is that NK1 receptor blockade has corresponding effects in humans and thus substantially reduces loss of plasma albumin during dialysis. Primary end point(s): Measurements are performed according to the PDC (Personal Dialysis Capacity) protocol whis is a clinical routine applied to PD patients. PDC quantitates the transperitoneal transport of water and solutes, including proteins, during dialysis in terms of the three‐pore model. In addition, concentrations of the cytokines IL‐1 beta, IL‐6, IL‐8, TNF alfa, NGF are measured in plasma and dialysate.; Primary end points are transperitoneal albumin transport and peritoneal release of IL‐1 beta, IL‐6, IL‐8, TNF alfa, NGF. Secondary Objective: Secondary objectives involve other known effects of neuropeptide release. Substance P propagates an inflammatory response by inducing the release of inflammatory cytokines. Hypothetically NK1 receptor blockade will also inhibit this effect, thereby reducing the negative long‐term effects of PD on peritoneal structure and function. Timepoint(s) of evaluation of this end point: Transperitoneal albumin transport is evaluated as part of the PDC evaluation within two weeks after the finalization of each treatment time period.; Evaluations of intraperitoneal cytokine release are performed whenever measurements of pooled samples are available, typically every three to six months. SECONDARY OUTCOME: Secondary end point(s): Secondary end points are the other measurements obtained from the PDC, i.e. peritoneal diffusion surface area, hydraulic conductivity and reabsorption. Timepoint(s) of evaluation of this end point: PDC evaluation is performed within two weeks after the finalization of each treatment time period. INCLUSION CRITERIA: Included persons are treated with PD since at least 3 months and are males aged 20‐90 or post‐menopausal females up to age 90. Included persons must have positive ultrafiltration (ultrafiltration volume larger than 0 ml/24 hours measured not more than one month earlier). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16