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Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial.
Ix, JH, Isakova, T, Larive, B, Raphael, KL, Raj, DS, Cheung, AK, Sprague, SM, Fried, LF, Gassman, JJ, Middleton, JP, et al
Journal of the American Society of Nephrology : JASN. 2019;(6):1096-1108
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Abstract
BACKGROUND Higher serum phosphate and fibroblast growth factor-23 (FGF23) levels may be modifiable to prevent cardiovascular disease in CKD. Short-term studies have reported modest efficacy in phosphate and FGF23 reduction with intestinal phosphate binders in CKD. METHODS To investigate effects of lanthanum carbonate (LC; a phosphate binder) and/or nicotinamide (NAM; an inhibitor of active intestinal phosphate transport) on serum phosphate and FGF23 in stage 3b/4 CKD, we conducted a randomized trial among individuals with eGFR 20-45 ml/min per 1.73 m2 to NAM (750 mg twice daily) plus LC (1000 mg thrice daily), NAM plus LC placebo, LC plus NAM placebo, or double placebo for 12 months. Dual primary end points were change from baseline in serum phosphate and intact FGF23 concentrations. RESULTS Mean eGFR for the 205 participants was 32ml/min per 1.73 m2. At baseline, serum phosphate was 3.7 mg/dl and median FGF23 was 99 pg/ml (10th, 90th percentiles: 59, 205). Mean rates of change in phosphate increased slightly over 12 months in all groups and did not differ significantly across arms. Similarly, percent changes in FGF23 per 12 months increased for all arms except LC plus placebo, and did not differ significantly across arms. Gastrointestinal symptoms limited adherence. Adverse events rates were similar across arms. CONCLUSIONS LC and/or NAM treatment did not significantly lower serum phosphate or FGF23 in stage 3b/4 CKD over 12 months. Although these agents appeared safe, intestinal symptoms limited adherence. Reducing phosphate and FGF23 in nondialysis CKD will require new approaches.
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[Genetic and immunologic risks for development of type 1 diabetes--experiences from an intervention trial].
Undlien, DE, Joner, G, Dahl-Jørgensen, K, Rønningen, KS, Nicol-Smith, L, Torjesen, PA, Søvik, O
Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. 2000;(23):2799-803
Abstract
BACKGROUND Type 1 diabetes is a common multi-factorial disease. Recently, promising attempts have been made at preventing the disease in individuals at risk. We present our experiences as participants in an international multicentre intervention trial, the European Nicotinamide Diabetes Intervention Trial (ENDIT). The aim is to prevent prediabetic individuals from becoming overtly diabetic by the use of nicotinamide. MATERIAL AND METHODS First degree relatives of type 1 diabetes children attending paediatric clinics in Norway were recruited. The level of islet cell antibodies (ICA) was determined. Individuals with ICA titer above 20 Juvenile Diabetes Foundation Units (JDFU) were allocated to treatment with nicotinamide or placebo in a double-blind design. In the Norwegian patients in the trial HLA-DQ genotypes were also determined. RESULTS 56 individuals had ICA > 20 JDFU; 36 agreed to participate in the trial. Assessment of genetic and immunological risk did not seem to emotionally upset the majority of participants; so far, no serious adverse events have been observed. The final results of this trial are expected in year 2003. INTERPRETATION Prevention of type 1 diabetes may be feasible in the future.