Conference: 2009 PH Resource Network Symposium
Release Date: 09.24.2009
Presentation Type: Abstracts
David Badesch, MD; Karen Fagan, MD; Deborah McCollister, RN, BSN; John Kittelson, PhD; Mark Tripputi, MS; Tom Yaeger, BS; Howard Weinberger, MD; John V Weil, MD
University of Colorado, Denver, CO; University of S. Alabama, Mobile, AL
BACKGROUND: Although small numbers of adults with PAH have received chronic inhaled nitric oxide (NO), long-term delivery has not been formally studied, and is expensive and complicated. NO synthases are present in endothelium and other cells. L-arginine (arg) is the sole substrate for these enzymes, and thus essential for NO production. Chronic L-arg administration ameliorates PH and vascular remodeling in rats. This small pilot study investigated the safety and pilot efficacy of chronic L-arg supplementation in humans with PAH, as measured by exercise capacity, right heart size and function, and systemic arterial function.
METHODS: 20 patients with WHO Group-1 PAH were entered into a 6-mo, single-center, randomized, double-blind, placebo-controlled safety-oriented pilot study of oral L-arg supplementation, comparing 1 gm PO QID to matching placebo on various safety parameters (potassium levels and adverse events (AEs)), as well as 6-minute walking distance (6MWD), 2-D echo parameters, and brachial arterial blood flow.
RESULTS: The treatment groups were well-matched at baseline in terms of 6MWD, NYHA functional class, estimated right ventricular systolic pressure (RVSP), age, and gender. After 6 mos of blinded therapy, there were no differences in potassium levels or AEs between treatment groups. Similarly, there were no significant differences in 6MWD expressed as change from baseline between treatment arms [mean(+SD): -28m(+80) and +40m(+66) for L-arg and placebo, respectively], or RVSP [7(+9) and 0(+10) respectively]. Other exploratory endpoints included RV diameter, RV index, and circulating arg levels.
CONCLUSIONS: This small, safety-oriented, pilot study of oral L-arg supplementation in PAH showed no differences in potassium levels or AEs, and no favorable trends in efficacy as assessed by 6MWD or estimated RVSP. The data need to be interpreted cautiously due to the small sample size.
FUNDING: NIH/NHLBI K24 HL04004-05; and NIH M01 RR00051-43