Clinical trial NCT05610956: Evaluate the Possible Efficacy and Safety of Empagliflozin in Patient With Ulcerative Colitis
Official title: Clinical Study to Evaluate the Possible Efficacy and Safety of Empagliflozin in Patients With Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Ulcerative Colitis
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2022-11-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel randomized controlled
Primary purpose: TREATMENT

Brief summary: •This study will be a randomized, controlled, parallel study. .To demonstrate the efficacy of empagliflozin and clinical improvement in patients of mild to moderate UC using the Montreal classification of severity of ulcerative colitis.

Detailed description: * It will be conducted on 60 patients having with mild to moderate degree UC divided into two groups:

  1. Group 1 (n=30): Patients will receive conventional treatment only (corticosteroids +immune suppressive +amino salicylic acid).
  2. Group 2 (n=30): Patients will receive conventional treatment (corticosteroids +immune suppressive + aminosalicylic acid) and empagliflozin (0.4 - 0.5mg/kg/day) orally (maximum dose 25mg per day).
* The patient will be selected from the Gastroenterology and Endoscopy Unit, Internal Medicine.

  . All patients will be subjected to the following:
* Complete history taking.
* Colonoscopy with intubation of the ileum and biopsies of affected and unaffected areas should be obtained to confirm the diagnosis of UC.
* Blood sample collection to assess:

A) Routine Laboratory tests

1. Complete blood picture (CBC).
2. Liver functions (ALT, AST, Total and Direct Bilirubin).
3. Kidney functions tests (Urea, serum creatinine).
4. C-reactive protein.
5. Fasting blood glucose.
6. Urine analysis. B) Specific Laboratory tests

1. Tumor necrosis factor alpha (TNF-α). 2. Adenosine monophosphate kinase (9AMPK). 3. Fecal calprotectin. All patients will be assessed at baseline and after 4 months of therapy for all parameters

Eligibility criteria: Inclusion Criteria:

•Patients with mild to moderate UC are diagnosed by history, clinical signs according to the Montreal classification of severity of ulcerative colitis and( Endoscopy, and biopsy) to establish the chronicity of inflammation and to exclude other causes of colitis.

Exclusion Criteria:

* Other inflammatory bowel diseases (CD).
* History of serious hypersensitivity to empagliflozin or any component of the formulation.
* Patients on dialysis.
* Severe renal impairment (eGFR \<20 ml/minute/1.73m2) .
* Chronic urinary tract infection.
* Chronic genital infection.

Primary outcomes:
measure: clinical improvement of patients of mild to moderate UC using using the Montreal classification of severity of ulcerative colitis.
timeFrame: 4months
Secondary outcomes:
measure: expression of TNFalpha
timeFrame: 4months
measure: expression of Adenosine monophosphate kinase (9AMPK ).
timeFrame: 4months
measure: expression of Fecal calprotectin
timeFrame: 4months
Other outcomes:
Locations:
Study officials:
References:
citation: Rubin DT, Huo D, Kinnucan JA, Sedrak MS, McCullom NE, Bunnag AP, Raun-Royer EP, Cohen RD, Hanauer SB, Hart J, Turner JR. Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study. Clin Gastroenterol Hepatol. 2013 Dec;11(12):1601-8.e1-4. doi: 10.1016/j.cgh.2013.06.023. Epub 2013 Jul 17.
citation: Gasche C, Scholmerich J, Brynskov J, D'Haens G, Hanauer SB, Irvine EJ, Jewell DP, Rachmilewitz D, Sachar DB, Sandborn WJ, Sutherland LR. A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis. 2000 Feb;6(1):8-15. doi: 10.1097/00054725-200002000-00002.
citation: Colman RJ, Rubin DT. Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review. Intest Res. 2016 Jul;14(3):202-10. doi: 10.5217/ir.2016.14.3.202. Epub 2016 Jun 27.
citation: Jess T, Frisch M, Simonsen J. Trends in overall and cause-specific mortality among patients with inflammatory bowel disease from 1982 to 2010. Clin Gastroenterol Hepatol. 2013 Jan;11(1):43-8. doi: 10.1016/j.cgh.2012.09.026. Epub 2012 Sep 27.
citation: Regueiro M, Greer JB, Szigethy E. Etiology and Treatment of Pain and Psychosocial Issues in Patients With Inflammatory Bowel Diseases. Gastroenterology. 2017 Feb;152(2):430-439.e4. doi: 10.1053/j.gastro.2016.10.036. Epub 2016 Nov 2.
citation: MacDermott RP, Sanderson IR, Reinecker HC. The central role of chemokines (chemotactic cytokines) in the immunopathogenesis of ulcerative colitis and Crohn's disease. Inflamm Bowel Dis. 1998 Feb;4(1):54-67. doi: 10.1097/00054725-199802000-00009.
citation: Greenstein AJ, Sachar DB, Gibas A, Schrag D, Heimann T, Janowitz HD, Aufses AH Jr. Outcome of toxic dilatation in ulcerative and Crohn's colitis. J Clin Gastroenterol. 1985 Apr;7(2):137-43. doi: 10.1097/00004836-198504000-00007.
citation: Jalan KN, Sircus W, Card WI, Falconer CW, Bruce CB, Crean GP, McManus JP, Small WP, Smith AN. An experience of ulcerative colitis. I. Toxic dilation in 55 cases. Gastroenterology. 1969 Jul;57(1):68-82. No abstract available.
citation: Bedine MS. Textbook of gastroenterology. Gastroenterology. 2000 May;118(5):984-5. doi: 10.1016/s0016-5085(00)70191-0. No abstract available.
citation: Bernstein CN, Wajda A, Blanchard JF. The incidence of arterial thromboembolic diseases in inflammatory bowel disease: a population-based study. Clin Gastroenterol Hepatol. 2008 Jan;6(1):41-5. doi: 10.1016/j.cgh.2007.09.016. Epub 2007 Dec 11.
citation: Merigo F, Brandolese A, Facchin S, Missaggia S, Bernardi P, Boschi F, D'Inca R, Savarino EV, Sbarbati A, Sturniolo GC. Glucose transporter expression in the human colon. World J Gastroenterol. 2018 Feb 21;24(7):775-793. doi: 10.3748/wjg.v24.i7.775.
citation: Zhou H, Wang S, Zhu P, Hu S, Chen Y, Ren J. Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission. Redox Biol. 2018 May;15:335-346. doi: 10.1016/j.redox.2017.12.019. Epub 2017 Dec 30.
citation: Iannantuoni F, M de Maranon A, Diaz-Morales N, Falcon R, Banuls C, Abad-Jimenez Z, Victor VM, Hernandez-Mijares A, Rovira-Llopis S. The SGLT2 Inhibitor Empagliflozin Ameliorates the Inflammatory Profile in Type 2 Diabetic Patients and Promotes an Antioxidant Response in Leukocytes. J Clin Med. 2019 Nov 1;8(11):1814. doi: 10.3390/jcm8111814.
citation: Karle EJ, Gehring F, Trautner K. [Cariogenic properties of various snacks in animal experiments]. Dtsch Zahnarztl Z. 1977 Sep;32(9):741-3. German.
citation: Esmat S, El Nady M, Elfekki M, Elsherif Y, Naga M. Epidemiological and clinical characteristics of inflammatory bowel diseases in Cairo, Egypt. World J Gastroenterol. 2014 Jan 21;20(3):814-21. doi: 10.3748/wjg.v20.i3.814.