EFFECTS OF N-ACETYL-L-CYSTEINE IN PATIENTS WITH CHRONIC ATROPHIC GASTRITIS AND NONULCER DYSPEPSIA - A PHASE-III PILOT-STUDY

Several studies have suggested that oxidative damage may contribute to gastritis. This damage is counteracted by various scavengers includin g glutathione (GSH), which may help defend the gastric mucosa. N-acety l-L-cysteine (NAC), a GSH precursor, could thus be of therapeutic inte rest. This multiple-dose, double-masked, randomized, parallel-group, p hase III pilot study was designed to assess the effects of NAC in 18 p atients undergoing upper gastrointestinal endoscopy for dyspepsia who had endoscopically and histologically confirmed chronic atrophic gastr itis but no peptic ulcer. Patients were randomly allocated to one of t hree treatment groups (NAC 1 g/d at bedtime, 1 g two times a day [2 g/ d], or 2 g two times a day [4 g/d]) for 4 weeks. After treatment, pati ents underwent a second endoscopy. During both endoscopies, multiple b iopsies were taken for histologic examination (based on a semiquantita tive score according to the Sydney system). Reduced/oxidized glutathio ne (GSH/GSSG) and malondialdehyde (MDA) were also measured (using high -performance liquid chromatography and fluorometric assay). At recruit ment, 6 patients tested negative and 12 tested positive for Helicobact er pylori. Serologic findings and symptoms (semi-quantitatively scored ) were collected at the beginning and end of the trial. After treatmen t, 13 (72%) of 18 patients showed improvement on endoscopy, irrespecti ve of NAC dose, and 5 (28%) showed no change. Histologically, polymorp h infiltration was significantly reduced in patients who received 2 g of NAC. The 5-point total symptom score was lower, but not significant ly so, in patients who received the other doses. Because of a high var iability, no significant change in GSH and MDA was found. No differenc e was observed between H pylori-positive and -negative patients. No re levant changes were detected in laboratory findings, and the most comm on adverse events were constipation, abdominal pain, and flatulence. O ur findings suggest that in patients with gastritis and nonulcer dyspe psia, NAC is fairly well tolerated and apparently leads to endoscopic, symptomatic, and to some extent histologic improvement, unrelated to changes in mucosal GSH levels.