Abstract 542: Effects of 1-Methylnicotinamide on Inflammatory and Lipid Biomarkers

Background: 1-methylnicotinamide, a nicotinic acid metabolite, is TRIA-662’s active component. As part of a pilot study, we assessed TRIA-662’s effects on inflammatory biomarkers and blood lipids. Methods: Patients aged 18-80 years with mean serum triglycerides (TG) 2.26-5.65 mmol/L, low-density lipoprotein-cholesterol levels not needing drug therapy, and stable diet and exercise regimens were randomized to TRIA-662 or placebo (PBO, 3:1) up-titrating to 6 g daily orally for 14 weeks. Outcomes were treatment compliance and changes from baseline in inflammatory biomarkers and blood lipids. Results: The 71 randomized patients were 54±12 years old, 54% were male, 48% were obese, 37% had hypertension, 25% dyslipidemia, and 7% diabetes. Treatment compliance and study completion (95% CI) were reached in 87.1% (79.3, 95.0%) and 87.3% (79.6, 95.1%) of patients overall, respectively. Adjusted geometric mean percent change (95% CI) from baseline in high-sensitivity C-reactive protein was -15.66% (-28.40, -0.66%) with TRIA-662 (p=0.0419 vs baseline) and 1.21% (-13.95, 19.05%) with PBO. The between-group difference of -16.67% (-33.59%, 4.57%) in favor of TRIA-662 did not reach significance (p=0.1130). The effect of TRIA-662 on tumor necrosis factor (TNF) alpha was influenced by the baseline value: For a baseline TNF value of 3.30 pg/mL (third quartile), the adjusted mean change (95% CI) was -0.65 (-0.92, -0.38) pg/mL, corresponding to a 20% decrease, with TRIA-662 and 0.31 (-0.32, 0.95) pg/ml, corresponding to a 9% increase with PBO, with a between-group difference of -0.97 (-1.65, -0.29) pg/mL (p=0.0076). The adjusted mean changes from baseline in adiponectin were 0.55 μg/mL (0.23, 0.86 μg/mL) corresponding to a 6% increase for TRIA-662 and -0.06 μg/mL (-0.53, 0.42 μg/mL) corresponding to a 0.7% decrease for PBO (p=0.0391 between groups). Geometric mean TG value at baseline was 3.36 mmol/L. The adjusted geometric mean percent change (95% CI) in TG was -9.01% (-15.91%, -1.54%) for TRIA-662 and -2.09% (-13.03, 10.24%) for PBO (p=0.3088 between groups). Baseline HDL-C was 1.01 ± 0.28 mmol/L, and the difference in change over time was not significant between groups (p=0.8242). Conclusion: TRIA-662 favourably affected inflammatory biomarkers in this pilot study.