Healing with basic fibroblast growth factor is associated with reduced indomethacin induced relapse in a human model of gastric ulceration.

Abstract

Background-Acid stable basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats and reduces subsequent non-steroidal anti-inflammatory drug (NSAID) induced relapse. Aims-To test in a double blind, placebo controlled, three way crossover study whether bFGF promotes healing and reduces subsequent relapse in a human model of gastric ulceration. Subjects-Twelve healthy volunteers. Methods-Subjects took aspirin 900 mg twice daily (days 1-3) with bFGF 01 mg twice daily or cimetidine 400 mg twice daily or placebo (days 1-14) and then indomethacin 50 mg thrice daily (days 15-21). Endoscopy was performed on days 1, 4, 8, 15, and 22 during each treatment period. Eight antral biopsy specimens were taken on day 1 and the number of unhealed biopsy induced mini-ulcers and NSAID induced erosions counted during subsequent endoscopies. Results-Basic FGF and cimetidine were protective against aspirin and indomethacin induced duodenal (but not gastric) injury compared with placebo. There was significant relapse of biopsy induced mini-ulcers after indomethacin only in the placebo group (0 (0-0) before v 1 (0-45) after; p>0'05). TGP-580 was detected in serum of one volunteer.Conclusions-Healing with bFGF (and cimetidine) was associated with reduced NSAID induced ulcer replapse in this model of gastric ulceration.

Role of growth factors and their receptors in gastric ulcer healing

“…In humans, the acid-stable mutein of bFGF, CS23, has been shown to accelerate ulcer healing in patients with treatment-refractory ulcerations due to non-steroidal anti-inflammatory drugs (Hull et al, 1995) and to reduce indomethacin induced gastric ulcer relapse (Hull et al, 1997).…”

Expression of Decorin and Biglycan in Rat Gastric Tissue: Effects of Ulceration and Basic Fibroblast Growth Factor

“…The availability of mice with interrupted genes for decorin and biglycan, respectively, opens up new ways for studying the role of the two proteoglycans during gastric ulcer healing in greater detail. However, from the data presented in this study it appears unlikely that the two proteoglycans participate in mediating the bene cial effect of an acid-stable FGF-2 analogue on ulcer healing previously described by us (22) as well as others (21).…”

“…Additionally, we have studied the in uence of intragastral application of an acidstable mutein of FGF-2 (CS23). FGF-2 has been shown to accelerate ulcer healing in animal models (20) as well as in man (21). In a previous study utilizing FGF-2, we demonstrated an increased matrix deposition upon CS23 application, whereas no differences in procollagen I mRNA (22) and the expression of matrix metalloproteinase-2 mRNA were found.…”

Endoscopy-Based Research in Healthy Volunteers

“…Although other studies [9] performed high quality procedures in a similar way, the number of endoscopies and/ or biopsies taken is subject to intensive discussion (table 5). We have just completed a study in HV, in which 10 individuals underwent a total of 8 endoscopies with a cumulative number of 240 biopsies.…”

“…Table 5. Study details of [9] 12 healthy volunteers Double-blind, three-way, placebo-controlled study 15 endoscopies and less than 48 biopsies/volunteer 1/12 could not tolerate endoscopy beyond first treatment period 9 episodes of adverse events, no serious adverse events Table 6. Key issues for ethical research involving HV Definition of limits (maximum number of biopsies, cross-over treatments, number of endoscopies, time for one endoscopy procedure) Limits for salary (to guarantee sufficient motivation for participation) Testing of clinically relevant outcomes (improved drug safety, drug interactions) Minimum follow-up observation period after study completion Application of same safety standards as in patient studies Obligatory report of discomfort/intolerance for future trials tified if the expected improvement in scientific knowledge is likely to contribute to routine clinical practice (e.g.…”