Geranylgeranylacetone protects against diclofenac-induced gastric and small intestinal mucosal injuries in healthy subjects: a prospective randomized placebo-controlled double-blind cross-over study.
OBJECTIVE
Little information is available regarding the prevention and treatment of small intestinal mucosal injuries caused by non-steroidal anti-inflammatory drugs (NSAIDs). We planned a pilot study to investigate the protective effects of geranylgeranylacetone (GGA) against NSAID-induced small intestinal injuries using video capsule endoscopy (VCE).


METHODS
Ten healthy male volunteers took oral GGA 300 mg/day (regimen A) or placebo (regimen B) in addition to diclofenac 75 mg/day + rabeprazole 20 mg/day for 7 days. We conducted a cross-over trial of regimens A and B with a 2-week washout period. All subjects underwent VCE before and after each administration period, and were evaluated for NSAID-induced gastric and small intestinal mucosal lesions.


RESULTS
The number of mucosal lesions (erosions, ulcers and a red spot with possible bleeding) detected in both stomach and small bowel changed between prior to and immediately after administration period, with significantly fewer lesions for regimen A after administration period (mean +/- SD A:B = 2.6 +/- 3.2:9.5 +/- 8.5; p = 0.027).


CONCLUSIONS
Combination therapy with GGA and rabeprazole reduced the incidence of gastroenteropathy induced by 1-week administration of diclofenac. Our findings suggest this therapy as a candidate for protecting patients on long-term NSAID therapy.
Niwa
Yasumasa
Y
Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan. yniwa@med.nagoya-u.ac.jp
Nakamura
Masanao
M
Miyahara
Ryoji
R
Ohmiya
Naoki
N
Watanabe
Osamu
O
Ando
Takafumi
T
Kawashima
Hiroki
H
Itoh
Akihiro
A
Hirooka
Yoshiki
Y
Goto
Hidemi
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D053704:Capsule Endoscopy; D018592:Cross-Over Studies; D004008:Diclofenac / Q000009:adverse effects*; D004224:Diterpenes / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D011446:Prospective Studies; D064750:Rabeprazole; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D004008:Diclofenac; D064750:Rabeprazole; C031049:geranylgeranylacetone