Dynamics of clinical manifestations of irritable bowel syndrome against the background of cytoprotector rebamipide intake: intermediate results of the SOKRAT program

Abstract

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common diseases of the gastrointestinal tract, the detection rate of which in the general population is 9-23%, in the Russian Federation – 8.3-19%. IBS is the cause of chronic pain which accompanies patients throughout their life, significantly reducing its quality and disrupting social adaptation. Insufficient effectiveness of modern methods of treating IBS dictates the need to search for new drugs, the pharmacological action of which is aimed at the pathogenetic mechanisms of IBS formation. Currently, more and more attention in the development of IBS is paid to the syndrome of increased epithelial permeability, in connection with which it is promising to include the universal cytoprotector rebamipide in the complex therapy of patients with IBS.

AIM: To evaluate the effect of rebamipide on the course of irritable bowel syndrome.

MATERIALS AND METHODS: This article presents the intermediate results of the SOCRAT study, which has assessed the effect of rebamipide on the course of IBS. For this purpose, 40 patients with IBS have been examined and subsequently randomized into two groups comparable in gender, age and type of IBS. The patients of the main group (n = 21) received cytoprotector rebamipide in addition to standard antispasmodic therapy, and the patients of the comparison group (n = 19) received cytoprotector bismuth tripotassium dicitrate. Patients’ gastroenterological complaints have been assessed before and after treatment using GSRS, 7x7, IBS-QOL questionnaires and a visual analogue scale.

RESULTS: According to the study findings, the well-being of the patients has improved in the both study groups. However, more significant positive dynamics has been observed in the main group, as evidenced by a significant decrease in the frequency and severity of abdominal pain and symptoms caused by constipation, which, in turn, led to an increase in the quality of life of the studied patients.

CONCLUSIONS: Thus, protective therapy of epithelium with rebamipide has not only a symptom-reducing effect, but also a positive effect on the course of IBS.

Keywords

irritable bowel syndrome / rebamipide / increased epithelial permeability syndrome / cytoprotector

References

[1] Aziz I, Palsson OS, Törnblom H, et al. The Prevalence and impact of overlapping rome IV-diagnosed functional gastrointestinal disorders on somatization, quality of life, and healthcare utilization: a cross-sectional general population study in three countries. Am J Gastroenterol. 2018;113(1):86–96. DOI: 10.1038/ajg.2017.421

[2] Aziz I., Palsson O.S., Törnblom H. et al. The prevalence and impact of overlapping rome IV-diagnosed functional gastrointestinal disorders on somatization, quality of life, and healthcare utilization: a cross-sectional general population study in three countries // Am. J. Gastroenterol. 2018. Vol. 113, No. 1. P. 86–96. DOI: 10.1038/ajg.2017.421

[3] Ambulatornaya gastroenterologiya. Rukovodstvo dlya vrachej. Ed. by I.G. Bakulin. Moscow; 2020. (In Russ.)

[4] Амбулаторная гастроэнтерология: руководство для врачей / под ред. И.Г. Бакулина. М., 2020.

[5] Ardatskaya MD, Topchy TB, Loschinina YuN, Kalashnikova MA. Clinical efficiency of butyric acid and inulin in rapid relief of pain syndrome in patients with irritable bowel syndrome. Lechaschi Vrach. 2015;(12):79–86. (In Russ.)

[6] Ардатская М.Д., Топчий Т.Б., Лощинина Ю.Н., Калашникова М.А. Клиническая эффективность масляной кислоты и инулина в купировании болевого синдрома у пациентов с синдромом раздраженной кишки // Лечащий врач. 2015. № 12. С. 79–86.

[7] Pushkina AV, Avalueva EB, Vorobiev SL. Immunohistochemical characteristics of the colonic mucosa in patients with irritable bowel syndrome. Gastroenterology of St. Petersburg. 2020;(3–4):3–12. (In Russ.)

[8] Пушкина А.В., Авалуева Е.Б., Воробьев С.Л. Иммуногистохимические характеристики слизистой оболочки толстой кишки у пациентов с синдромом раздраженного кишечника // Гастроэнтерология Санкт-Петербурга. 2020. № 3–4. С. 3–12.

[9] El Serag HB, Olden K, Bjorkman D. Healthrelated quality of life among persons with irritable bowel syndrome: a systematic review. Aliment Pharmacol Ther. 2002;16(6):1171–1185. DOI: 10.1046/j.1365-2036.2002.01290.x

[10] El Serag H.B., Olden K., Bjorkman D. Healthrelated quality of life among persons with irritable bowel syndrome: a systematic review // Aliment. Pharmacol. Ther. 2002. Vol. 16, No. 6. P. 1171–1185. DOI: 10.1046/j.1365-2036.2002.01290.x

[11] Baranovsky AYu, Wasserman LI, Fedorova VL, Chugunov DN. Irritable bowel syndrome: clinical, psychological and psychosocial interdependence. Experimental and Clinical Gastroenterology. 2019;(12(172)):3. (In Russ.). DOI: 10.31146/1682-8658-ecg-172-12-34-39

[12] Барановский А.Ю., Вассерман Л.И., Федорова В.Л., Чугунов Д.Н. Синдром раздраженной кишки: клинико-психологические и психосоциальные соотношения // Экспериментальная и клиническая гастроэнтерология. 2019. № 12(172). С. 34–39. DOI: 10.31146/1682-8658-ecg-172-12-34-39

[13] Simanenkov VI, Maev IV, Tkacheva ON, et al. Syndrome of increased epithelial permeability in clinical practice. Multidisciplinary national Consensus. Cardiovascular Therapy and Prevention. 2021;20(1):121–278. (In Russ.). DOI: 10.15829/1728-8800-2021-2758

[14] Симаненков В.И., Маев И.В., Ткачева О.Н. и др. Синдром повышенной эпителиальной проницаемости в клинической практике. Мультидисциплинарный национальный консенсус // Кардиоваскулярная терапия и профилактика. 2021. Т. 20, № 1. С. 121–278. DOI: 10.15829/1728-8800-2021-2758

[15] Klinicheskie rekomendacii. Sindrom razdrazhennogo kishechnika. 2021–2023 [Internet]. Minzdrav RF. Available from: https://legalacts.ru/doc/klinicheskie-rekomendatsii-sindrom-razdrazhennogo-kishechnika-utv-minzdravom-rossii/. Accessed: Sep 15, 2021. (In Russ.)

[16] Клинические рекомендации. Синдром раздраженного кишечника. 2021–2023 [Электронный ресурс] // Минздрав РФ. Режим доступа: https://legalacts.ru/doc/klinicheskie-rekomendatsii-sindrom-razdrazhennogo-kishechnika-utv-minzdravom-rossii/. Дата обращения: 15.09.2021.

[17] Sheptulin A, Vize-Khripunova MA. Review of Rome-IV criteria for the irritable bowel syndrome: are there any basic changes? Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016;26(5):99–103. (In Russ.). DOI: 10.22416/1382-4376-2016-26-5-99-103

[18] Шептулин А.А., Визе-Хрипунова М.А. Римские критерии синдрома раздраженного кишечника IV пересмотра: есть ли принципиальные изменения? // Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2016. Т. 26, № 5. С. 99–103. DOI: 10.22416/1382-4376-2016-26-5-99-103

[19] Ivashkin VT, Shelygin YA, Baranskaya EK, et al. Clinical recommendations of the Russian Gastroenterological Association and the Association of Coloproctologists of Russia for the diagnosis and treatment of irritable bowel syndrome. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2017;27(5):76–93. (In Russ.). DOI: 10.22416/1382-4376-2017-27-5-76-93

[20] Ивашкин В.Т., Шелыгин Ю.А., Баранская Е.К. и др. Клинические рекомендации Российской гастроэнтерологической ассоциации и Ассоциации колопроктологов России по диагностике и лечению синдрома раздраженного кишечника // Российский журнал гастроэнтерологии, гепатологии и колопроктологии. 2017. Т. 27, № 5. С. 76–93. DOI: 10.22416/1382-4376-2017-27-5-76-93

[21] Barbalho SM, Goulart RA, Araújo AC, et al. Iirritable bowel syndrome: a review of the general aspects and the potential role of vitamin D. Expert Rev Gastroenterol Hepatol. 2019;13(4):345–359. DOI: 10.1080/17474124.2019.1570137

[22] Barbalho S.M., Goulart R.A., Araújo A.C. et al. Iirritable bowel syndrome: a review of the general aspects and the potential role of vitamin D // Expert. Rev. Gastroenterol. Hepatol. 2019. Vol. 13, No. 4. P. 345–359. DOI: 10.1080/17474124.2019.1570137

[23] Ivashkin VT, Zolnikova OYu. Irritable bowel syndrome in terms of changes in the microbiota. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(1):84–92. (In Russ.). DOI: 10.22416/1382-4376-2019-29-1-84-92

[24] Ивашкин В.Т., Зольникова О.Ю. Синдром раздраженного кишечника с позиций изменений микробиоты // Российский журнал гастроэнтерологии, гепатологии и колопроктологии. 2019. Т. 29, № 1. С. 84–92. DOI: 10.22416/1382-4376-2019-29-1-84-92

[25] Andreev DN. The role of alterations in permeability of the intestinal mucosa in the genesis of functional gastrointestinal disorders. Consilium Medicum. 2019;21(8):29–34. (In Russ.). DOI: 10.26442/20751753.2019.8.190539

[26] Aндреев Д.Н. Роль нарушения проницаемости слизистой оболочки кишечника в генезе функциональных заболеваний желудочно-кишечного тракта // Consilium Medicum. 2019. Т. 21, № 8. С. 29–34. DOI: 10.26442/20751753.2019.8.190539

[27] Casado-Bedmar M, Keita AV. Potential neuro-immune therapeutic targets in irritable bowel syndrome. Therap Adv Gastroenterol. 2020;13:1756284820910630. DOI: 10.1177/1756284820910630

[28] Casado-Bedmar M., Keita A.V. Potential neuro-immune therapeutic targets in irritable bowel syndrome // Therap. Adv. Gastroenterol. 2020. Vol. 13. P. 1756284820910630. DOI: 10.1177/1756284820910630

[29] Choghakhori R, Abbasnezhad A, Hasanvand A, Amani R. Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: Association with digestive symptoms and quality of life. Cytokine. 2017;93:34–43. DOI: 10.1016/j.cyto.2017.05.005

[30] Choghakhori R., Abbasnezhad A., Hasanvand A., Amani R. Inflammatory cytokines and oxidative stress biomarkers in irritable bowel syndrome: Association with digestive symptoms and quality of life // Cytokine. 2017. Vol. 93. P. 34–43. DOI: 10.1016/j.cyto.2017.05.005

[31] Farzaei MH, Bahramsoltani R, Abdollahi M, Rahimi R. The role of visceral hypersensitivity in irritable bowel syndrome: pharmacological targets and novel treatments. Neurogastroenterol Motil. 2016;22(4):558–574. DOI: 10.5056/jnm16001

[32] Farzaei M.H., Bahramsoltani R., Abdollahi M., Rahimi R. The role of visceral hypersensitivity in irritable bowel syndrome: pharmacological targets and novel treatments // Neurogastroenterol. Motil. 2016. Vol. 22, No. 4. P. 558–574. DOI: 10.5056/jnm16001

[33] Farré R, Vanheel H, Vanuytsel T, et al. In functional dyspepsia, hypersensitivity to postprandial distention correlateswwith mealrelated symptom severity. Gastroenterology. 2013;145(3):566–573. DOI: 10.1053/j.gastro.2013.05.018

[34] Farré R., Vanheel H., Vanuytsel T. et al. In functional dyspepsia, hypersensitivity to postprandial distention correlateswwith mealrelated symptom severity // Gastroenterology. 2013. Vol. 145, No. 3. P. 566–573. DOI: 10.1053/j.gastro.2013.05.018

[35] Ludidi S, Mujagic Z, Jonkers D, et al. Markers for visceral hypersensitivity in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2014;26(8):1104–1111. DOI: 10.1111/nmo.12365

[36] Ludidi S., Mujagic Z., Jonkers D. et al. Markers for visceral hypersensitivity in patients with irritable bowel syndrome // Neurogastroenterol. Motil. 2014. Vol. 26, No. 8. P. 1104–1111. DOI: 10.1111/nmo.12365

[37] Kanazawa M, Palsson OS, Thiwan SМ, et al. contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits. Am J Gastroenterol. 2008;103(10):2550–2561. DOI: 10.1111/j.1572-0241.2008.02066.x

[38] Kanazawa M., Palsson O.S., Thiwan S.М. et al. contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits // Am. J. Gastroenterol. 2008. Vol. 103, No. 10. P. 2550–2561. DOI: 10.1111/j.1572-0241.2008.02066.x

[39] Coss-Adame E, Rao SS. Brain and gut interactions in irritable bowel syndrome: new paradigms and new understandings. Curr Gastroenterol Rep. 2014;16(4):379. DOI: 10.1007/s11894-014-0379-z

[40] Coss-Adame E., Rao S.S. Brain and gut interactions in irritable bowel syndrome: new paradigms and new understandings // Curr. Gastroenterol. Rep. 2014. Vol. 16, No. 4. P. 379. DOI: 10.1007/s11894-014-0379-z

[41] Johansso MEV, Sjövall H, Hansson GC. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol. 2013;10(6):352–361. DOI: 10.1038/nrgastro.2013.35

[42] Johansson M.E.V., Sjövall H., Hansson G.C. The gastrointestinal mucus system in health and disease // Nat. Rev. Gastroenterol. Hepatol. 2013. Vol. 10, No. 6. P. 352–361. DOI: 10.1038/nrgastro.2013.35

[43] Simanenkov VI, Lutaenko EA, Nikogosyan AA. Clinical and pharmacological characteristics of rebamipide in deseases of the gastrointestinal tract. Medical Council. 2016;(19):88–95. (In Russ.). DOI: 10.21518/2079-701X-2016-19-88-95

[44] Симаненков В.И., Лутаенко Е.А., Никогосян А.А. Клинико-фармакологические особенности применения ребамипида при заболеваниях желудочно-кишечного тракта // Медицинский совет. 2016. № 19. С. 88–95. DOI: 10.21518/2079-701X-2016-19-88-95

[45] Simanenkov VI, Tikhonov SV. Rebamipide: new opportunities for gastroenteroprotection. Therapeutic Archive. 2015;87(12):134–137. (In Russ.). DOI: 10.17116/terarkh20158712134-137

[46] Симаненков В.И., Тихонов С.В. Ребамипид — новые возможности гастроэнтеропротекции // Терапевтический архив. 2015. Т. 87, № 12. С.134–137. DOI: 10.17116/terarkh20158712134-137

[47] Punkina AV, Avalueva EB, Ellinidi VN, et al. Optimizatsiya nekotorykh pokazateley lokal’nogo immuniteta patsientov s sindromom razrazhennogo kishechnika pri lechenii preparatom vismuta. Gastroenterologiya Sankt-Peterburga. 2016;(1–2):11–14. (In Russ.)

[48] Пушкина А.В., Авалуева Е.Б., Эллиниди В.Н. и др. Оптимизация некоторых показателей локального иммунитета пациентов с синдромом раздраженного кишечника при лечении препаратом висмута // Гастроэнтерология Санкт-Петербурга. 2016. № 1–2. С. 11–14.

[49] Punkina AV, Avalueva EB, Danilova IA, et al. Ispol’zovanie preparatov vismuta trikaliya ditsitrata v lechenii sindroma razdrazhennogo kishechnika s preobladaniem diarei. Lechashchiy vrach. 2016;6:81–84. (In Russ.)

[50] Пушкина А.В., Авалуева Е.Б., Данилова И.А. и др. Использование препарата висмута трикалия дицитрата в лечении синдрома раздраженного кишечника с преобладанием диареи // Лечащий врач. 2016. № 6. С. 81–84.

[51] Simanenkov VI, Bakulina NV, Tikhonov SV. Bismuth tripotassium dicitrat: from pharmaceutical characteristics to clinical efficacy. Medical Alphabet. 2019;1(6(381)):23–28. (In Russ.). DOI: 10.33667/2078-5631-2019-1-6(381)-23-28

[52] Симаненков В.И., Бакулина Н.В., Тихонов С.В. Препараты висмута трикалия дицитрата: от фармацевтических характеристик к клинической эффективности // Медицинский алфавит. 2019. Т. 1, № 6(381). С. 23–28. DOI: 10.33667/2078-5631-2019-1-6(381)-23-28

[53] Tkachenko EI, Avalueva EB, Sitkin SI, et al. Ispol’zovanie preparatov vismuta v lechenii sindroma razdrazhennogo kishechnika. Gastroenterologiya Sankt-Peterburga. 2013;(3–4):11–14. (In Russ.)

[54] Ткаченко Е.И., Авалуева Е.Б., Ситкин С.И. и др. Использование препаратов висмута в лечении синдрома раздраженного кишечника // Гастроэнтерология Санкт-Петербурга. 2013. № 3–4. С. 11–14.

[55] Tarnawski AS, Chai J, Pai R, Chiou SK. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? Dig Dis Sci. 2004;49(2):202–209. DOI: 10.1023/b:ddas.0000017439.60943.5c

[56] Tarnawski A.S., Chai J., Pai R., Chiou S.K. Rebamipide activates genes encoding angiogenic growth factors and Cox2 and stimulates angiogenesis: a key to its ulcer healing action? // Dig. Dis. Sci. 2004. Vol. 49, No. 2. P. 202–209. DOI: 10.1023/b:ddas.0000017439.60943.5c

[57] Arakawa T, Kobayashi K, Yoshikawa T, Tarnawski A. Rebamipide: overview of its mechanisms of action and efficacy in mucosal protection and ulcer healing. Dig Dis Sci. 1998;43(9):5–13.

[58] Arakawa T., Kobayashi K., Yoshikawa T., Tarnawski A. Rebamipide: overview of its mechanisms of action and efficacy in mucosal protection and ulcer healing // Dig. Dis. Sci. 1998. Vol. 43, No. 9. P. 5–13.

[59] Nishizawa T, Suzuki H, Nakagawa I, et al. Rebamipide - promoted restoration of gastric mucosal sonic hedgehog expression after early Helicobacter pylori eradication. Digestion. 2009;79(4):259–262. DOI: 10.1159/000213241

[60] Nishizawa T., Suzuki H., Nakagawa I. et al. Rebamipide-promoted restoration of gastric mucosal sonic hedgehog expression after early Helicobacter pylori eradication // Digestion. 2009. Vol. 79, No. 4. P. 259–262. DOI: 10.1159/000213241

[61] Suzuki T, Yoshida N, Nakabe N, et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci. 2008;106(3):469–477. DOI: 10.1254/jphs.fp0071422

[62] Suzuki T., Yoshida N., Nakabe N. et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution // J. Pharmacol. Sci. 2008. Vol. 106, No. 3. P. 469–477. DOI: 10.1254/jphs.fp0071422

RIGHTS & PERMISSIONS

Simanenkov V.I., Bakulina N.V., Nekrasova A.S., Elokhina E.A., Topalova Y.G.