Recruiting young pre-symptomatic children for a clinical trial in type 1 diabetes: insights from the Fr1da insulin intervention study

Background: Although detection of children at high risk of developing type 1 diabetes and diagnosis of early stages is possible, up to now there exists no approved therapy to delay or prevent type 1 diabetes. Thus it is vital to develop evidence-based interventions. For this a sufficient number of trial participants is crucial but difficult to obtain especially in asymptomatic children. Aim: Identifying family characteristics that lead to or impede trial participation and analyze reasons stated by families for non-participation. Methods: Participants for the Fr1da Insulin Intervention study are recruited from the Fr1da study, a population based screening for early stage type 1 diabetes in Bavaria. Families with eligible children were invited to enroll. We analyzed sex and age of the child, distance of the family to the study center in Munich and the existence of a first degree family member with type 1 as possible influential factors for study participation. We also analyzed reasons stated by families who declined study participation in a phone interview. Results: Of 146 eligible children 77 (53%) were enrolled into the trial. None of the tested family characteristics differed significantly between the enrolling and the families not participating, but in general enrolling families lived closer to the study site than families not participating. This is also reflected in the reasons given by non-participating families. The most frequent reason stated were time restrictions. The second most frequent reason was the venous blood draw. Conclusion: The factors for non-participation identified in this project need be taken into account for the design of future trials in young children to ensure proper recruitment and thus to generate valid results for medical treatment of children. More research on the reason of participation and non-participation in clinical trials is needed. Keywords: Type 1 diabetes, Trial recruitment, Trial enrollment, Infants, Children, Asymptomati

Impact of Regular or Extended Hemodialysis and Hemodialfiltration on Plasma Oxalate Concentrations in Patients With End-Stage Renal Disease

Calcium oxalate supersaturation is regularly exceeded in the plasma of patients with end-stage renal disease (ESRD). Previous reports have indicated that hemodialfiltration (HDF) lowers elevated plasma oxalate (POx) concentrations more effectively compared with hemodialysis (HD). We reevaluate the therapeutic strategy for optimized POx reduction with advanced dialysis equipment and provide data on the effect of extended treatment time on dialytic oxalate kinetics. Methods: Fourteen patients with ESRD who underwent HDF 3 times a week for 4 to 4.5 hours (regular HDF; n = 8) or 7 to 7.5 hours (extended HDF; n = 6) were changed to HD for 2 weeks and then back to HDF for another 2 weeks. POx was measured at baseline, pre-, mid-, and postdialysis, and 2 hours after completion of the treatment session. Results: Baseline POx for all patients averaged 28.0 ± 7.0 μmol/l. Intradialytic POx reduction was approximately 90% and was not significantly different between groups or treatment modes [F(1) = 0.63; P = 0.44]. Mean postdialysis POx concentrations were 3.3 ± 1.8 μmol/l. A rebound of 2.1 ± 1.9 μmol/l was observed within 2 hours after dialysis. After receiving 2 weeks of the respective treatment, predialysis POx concentrations on HD did not differ significantly from those on HDF [F(1) = 0.21; P = 0.66]. Extended treatment time did not provide any added benefit [F(1) = 0.76; P = 0.40]. Discussion: In contrast to earlier observations, our data did not support a benefit of HDF over HD for POx reduction. With new technologies evolving, our results emphasized the need to carefully reevaluate and update traditional therapeutic regimens for optimized uremic toxin removal, including those used for oxalate