Role of Roflumilast in Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

Clinical Study to Evaluate the Possible Efficacy and Safety of Roflumilast in Patients With Ulcerative Colitis.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05684484
• Other study ID #: Roflumilast ulcerative colitis
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: February 1, 2023
• Est. completion date: November 2024

Study information

• Verified date: January 2023
• Source: Tanta University
• Contact: ahmed m. youness, master degree
• Phone: 0020114718892
• Email: ahmedyounes881[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to investigate possible efficacy and safety of Roflumilast in adult patients with ulcerative colitis disease .

Description:

- Study design and study population This study will be randomized, controlled, parallel study. - It will be conducted on 52 patient having with mild to moderate degree ulcerative colitis disease divided into two groups 1. Group 1 (n=26): Patients will receive conventional treatment only (corticosteroids +immune suppressive +amino salicylic acid) for 3 months. 2. Group 2 (n=26): Patients will receive previous conventional treatment and Roflumilast (500 mcg ) orally once daily for 3 months - Patient will be selected from Gastroenterology and Endoscopy Unit, Internal Medicine Department, Tanta University Hospital. - A written informed consent will be obtained from all patients - This study will be approved by the Research Ethics Committee of Tanta University. - Any unexpected risks appeared during the course of research will be reported to the participants and ethical committee on time and documented through an adverse effects reporting form . - Randomization will be carried out based on days of hospital admission

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 52
• Est. completion date: November 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients referred to endoscopy units in Tanta University hospitals during the period of the study.

Patient with mild to moderate UC diagnosed as:

1. Clinical signs: Patients with moderate clinical disease have frequent loose, bloody stools (>4per day), mild anemia, and abdominal pain that is not severe. Patients have minimal signs of systemic toxicity, including a low-grade fever. Adequate nutrition is usually maintained, and weight loss.

2. Endoscopy : are necessary to establish the chronicity of inflammation and to exclude other causes of colitis.

Exclusion Criteria:

• Other inflammatory bowel disease (crohn's disease) .
• Patients <15 and >80 years
• Patients who didn't give consent to participate in the study
• Patients with contraindications of colonoscopy e.g. suspected colonic perforation, acute peritonitis, pregnancy, severe bleeding tendency, shock, uncooperative patient and if toxic mega colon is suspected were excluded
• History of allergic reaction to Roflumilast or any component of the formulation Like rash , hives ,itching and redness .
• Depression , thoughts of suicide , anxiety and emotional instability .
• Excessive weight loss .
• Moderate to severe hepatic impairment (child pugh class B or C) .
• Strong (CYP3A4) inducers : Barbiturates (phenobarbital) , Carbamazepine , Phenytoin , Rifampicin ( Risk , X interaction )
• Loxapine ( Risk , X interaction )

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Roflumilast 500 Ug ORAL TABLET [Daliresp]
Roflumilast has been approved by U.S. Food and Drug Administration (FDA) for attenuating bronchial and dermatological disorders
• corticosteroids +immune suppressive +amino salicylic acid
conventional treatment

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

References & Publications (16)

de Souza HSP, Fiocchi C, Iliopoulos D. The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol. 2017 Dec;14(12):739-749. doi: 10.1038/nrgastro.2017.110. Epub 2017 Aug 23. — View Citation

Elbadry M, Nour MO, Hussien M, Ghoneem EA, Medhat MA, Shehab H, Galal S, Eltabbakh M, El-Raey F, Negm M, Afify S, Abdelhamed W, Sherief A, Abdelaziz A, Abo Elkasem M, Mahrous A, Kamal G, Maher M, Abdel-Hameed O, Elbasuny A, El-Zayyadi I, Bassiony A, Moussa A, Bedewy E, Elfert A, El Kassas M. Clinico-Epidemiological Characteristics of Patients With Inflammatory Bowel Disease in Egypt: A Nationwide Multicenter Study. Front Med (Lausanne). 2022 Apr 19;9:867293. doi: 10.3389/fmed.2022.867293. eCollection 2022. — View Citation

Faleiro L, Kobayashi R, Fearnhead H, Lazebnik Y. Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells. EMBO J. 1997 May 1;16(9):2271-81. doi: 10.1093/emboj/16.9.2271. — View Citation

Feuerstein JD, Cheifetz AS. Ulcerative colitis: epidemiology, diagnosis, and management. Mayo Clin Proc. 2014 Nov;89(11):1553-63. doi: 10.1016/j.mayocp.2014.07.002. Epub 2014 Sep 8. — View Citation

Fujita Y, Khateb A, Li Y, Tinoco R, Zhang T, Bar-Yoseph H, Tam MA, Chowers Y, Sabo E, Gerassy-Vainberg S, Starosvetsky E, James B, Brown K, Shen-Orr SS, Bradley LM, Tessier PA, Ronai ZA. Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines Intestinal Inflammation and Severity of Colitis. Cell Rep. 2018 Sep 18;24(12):3296-3311.e6. doi: 10.1016/j.celrep.2018.08.057. — View Citation

Kokkonen K, Kass DA. Nanodomain Regulation of Cardiac Cyclic Nucleotide Signaling by Phosphodiesterases. Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:455-479. doi: 10.1146/annurev-pharmtox-010716-104756. Epub 2016 Oct 12. — View Citation

Kosutova P, Mikolka P, Kolomaznik M, Balentova S, Adamkov M, Calkovska A, Mokra D. Reduction of lung inflammation, oxidative stress and apoptosis by the PDE4 inhibitor roflumilast in experimental model of acute lung injury. Physiol Res. 2018 Dec 31;67(Suppl 4):S645-S654. doi: 10.33549/physiolres.934047. — View Citation

Li H, Fan C, Feng C, Wu Y, Lu H, He P, Yang X, Zhu F, Qi Q, Gao Y, Zuo J, Tang W. Inhibition of phosphodiesterase-4 attenuates murine ulcerative colitis through interference with mucosal immunity. Br J Pharmacol. 2019 Jul;176(13):2209-2226. doi: 10.1111/bph.14667. Epub 2019 May 17. — View Citation

Li H, Li J, Zhang X, Feng C, Fan C, Yang X, Zhang R, Zhu F, Zhou Y, Xu Y, Liu H, Tang W. DC591017, a phosphodiesterase-4 (PDE4) inhibitor with robust anti-inflammation through regulating PKA-CREB signaling. Biochem Pharmacol. 2020 Jul;177:113958. doi: 10.1016/j.bcp.2020.113958. Epub 2020 Apr 3. — View Citation

Neurath MF. Targeting immune cell circuits and trafficking in inflammatory bowel disease. Nat Immunol. 2019 Aug;20(8):970-979. doi: 10.1038/s41590-019-0415-0. Epub 2019 Jun 24. — View Citation

Raker VK, Becker C, Steinbrink K. The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases. Front Immunol. 2016 Mar 31;7:123. doi: 10.3389/fimmu.2016.00123. eCollection 2016. — View Citation

Thrash B, Patel M, Shah KR, Boland CR, Menter A. Cutaneous manifestations of gastrointestinal disease: part II. J Am Acad Dermatol. 2013 Feb;68(2):211.e1-33; quiz 244-6. doi: 10.1016/j.jaad.2012.10.036. — View Citation

Trivedi PJ, Adams DH. Chemokines and Chemokine Receptors as Therapeutic Targets in Inflammatory Bowel Disease; Pitfalls and Promise. J Crohns Colitis. 2018 Nov 28;12(12):1508. doi: 10.1093/ecco-jcc/jjy130. No abstract available. — View Citation

Zebda R, Paller AS. Phosphodiesterase 4 inhibitors. J Am Acad Dermatol. 2018 Mar;78(3 Suppl 1):S43-S52. doi: 10.1016/j.jaad.2017.11.056. Epub 2017 Dec 15. — View Citation

Zhang X, Dong G, Li H, Chen W, Li J, Feng C, Gu Z, Zhu F, Zhang R, Li M, Tang W, Liu H, Xu Y. Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. J Med Chem. 2019 Jun 13;62(11):5579-5593. doi: 10.1021/acs.jmedchem.9b00518. Epub 2019 May 31. — View Citation

Zundler S, Becker E, Schulze LL, Neurath MF. Immune cell trafficking and retention in inflammatory bowel disease: mechanistic insights and therapeutic advances. Gut. 2019 Sep;68(9):1688-1700. doi: 10.1136/gutjnl-2018-317977. Epub 2019 May 24. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	clinical improvement in ulcerative colitis severity	To demonstrate the efficacy of Roflumilast and clinical improvement in (Mayo disease activity index) for assessment of ulcerative colitis severity	3 months
Secondary	changes in serum levels of the measured biochemical parameters	demonstrate changes in serum levels of the measured biochemical parameters; Tumor necrosis factor-alpha (TNF-a) as pro inflammatory marker (ELISA).; Signal transducer and activator of transcription 3 (STAT3) as a potential marker for apoptosis ( ELISA); Caspase-3 as a potential marker for apoptosis (ELISA).	7 months