A Potential Role of Ethosuximide and Pentoxifylline in Relieving Abdominal Pain in Irritable Bowel Syndrome Patients Treated with Mebeverine: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background and Purpose Irritable bowel syndrome (IBS) is defined as an association of chronic abdominal pain with bowel habit abnormalities, without clear organic dysfunction. T-type calcium channels and low-grade mucosal inflammation are linked to abdominal pain; however, medical treatments for IBS abdominal pain are largely ineffective. In this study, we investigated if pentoxifylline (PTX) and ethosuximide could potentially alleviate abdominal pain in patients with IBS treated with mebeverine. Methods We recruited 150 patients from Tanta University Hospital to this randomized, prospective, and double blinded study. Patients were randomly allocated to three groups (n = 50). Group 1 (mebeverine) received 135 mg mebeverine three times/day (t.i.d). Group 2 (ethosuximide group) received 135 mg mebeverine t.i.d plus 250 mg ethosuximide twice daily (b.i.d) and group 3 (PTX group) received 135 mg mebeverine t.i.d plus 400 mg PTX b.i.d. Patients were assessed by a gastroenterologist at baseline and 6 months after therapy. Serum interleukin-8 (IL-8), IL-6, tumor necrosis-α (TNF-α), fecal myeloperoxidase, and fecal neutrophil gelatinase associated lipocalin (NGAL) levels were measured before and after therapy. The numeric pain rating scale (NRS) was also assessed before and after therapy. Primary Outcomes Reduced NRS scores and abdominal pain relief. Secondary Outcomes Decreased inflammatory biomarkers. Results After 6 months, groups 2 and 3 showed a significantly greater reduction in serum IL-8, IL-6, TNF-α, fecal myeloperoxidase, and fecal NGAL levels when compared to group 1 after therapy. Both groups 2 and 3 showed significant reductions in NRS scores when compared to the group 1. Conclusion Ethosuximide and PTX may be promising, novel adjunct drugs to antispasmodics for relieving abdominal pain in patients with IBS. Trial Registration Identifier: NCT04217733.

Concerns about data integrity of 30 randomized clinical trials from one author.

“…One has been retracted. (12) 16 were retrospectively registered and 7 were prospectively registered (Table 3). Studies were submitted at regular intervals between 2016 and 2022 (Figure 1).…”

“…Since then, four COVID-19 RCTs, one Gastroenterology RCT (co-)authored by Dr Abd-Elsalam, and one COVID-19 RCT by another author within the same network have been retracted. The underlying datasets of these retracted RCTs showed clear signs of data-fabrication, including data-copying between different study databases (7)(8)(9)(10)(11)(12) In view of the above, we decided to investigate all RCTs published by Dr Abd-Elsalam.…”

Logistic Regression Analysis of Clinical Characteristics for Differentiation of Chronic Obstructive Pulmonary Disease Severity

“…As emerging inflammatory indicators, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are derived from the complete blood count and all are related to the degree of inflammation and clinical symptoms of COPD [ 9 , 10 ]. Elevated NLR levels have been reported in thyroid conditions [ 11 ], irritable bowel disease [ 12 ], COVID-19 infection [ 13 ], diabetes mellitus [ 14 ], and thyroiditis [ 15 ]. However, the use of blood count indicators and their derivatives in the classification of COPD severity has rarely been reported.…”