Safety and Effectiveness of Sulfasalazine in the Treatment of Liver Fibrosis/Cirrhosis.

NCT06293378 | Recruiting

• 1 other identifier: Pengmingli
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 2

Brief Summary

This is a controlled, observational clinical study initiated by investigators to investigate the efficacy and safety of sulfasalazine in the treatment of cirrhosis in patients with cirrhosis. Four cohorts were planned: primary biliary cirrhosis, hepatitis B and C cirrhosis, and alcoholic cirrhosis. The four groups were divided into experimental group and control group, and the experimental group: each group of patients was orally treated sulfasalazine for 12 months, taken three times a day, each time taking 0.5g. The control group did not take sulfasalazine. After 12 months, Observe changes in patients' biochemical and imaging indicators, liver stiffness values, fecal microbiota, and metabolites before and after the use of sulfasalazine.

Conditions

Cirrhosis, Liver; Fibrosis, Liver

Outcome Measures

Primary Outcomes (7)

• Hepatic fibrosis

  The changes of liver fibrosis

  baseline，1,3,6,9,12 months after treatment and 1 month after the end of treatment.

• Serum alkaline phosphatase (ALP)

  Serum alkaline phosphatase (ALP) level

  baseline,1,3,6,9,12 months after treatment and 1 month after the end of treatment.

• Serum γ-glutamyl transpeptidase (GGT)

  Serum γ-glutamyl transpeptidase (GGT) level

  baseline,1,3,6,9,12 months after treatment and 1 month after the end of treatment.

• Serum bilirubin

  Serum bilirubin level

  baseline,1,3,6,9,12 months after treatment and 1 month after the end of treatment.

• Serum bile acids

  Serum bile acids level

  baseline,1,3,6,9,12 months after treatment and 1 month after the end of treatment.

• Serum aspartate aminotransferase(AST)

  Serum aspartate aminotransferase(AST) level

  baseline,1,3,6,9,12 months after treatment and 1 month after the end of treatment.

• Serum alanine aminotransferase (ALT)

  Serum alanine aminotransferase (ALT) level

  baseline,1,3,6,9,12 months after treatment and 1 month after the end of treatment.

Secondary Outcomes (1)

• The gut microbiota and metabolites.

  baseline,1,3,6,9,12 months after treatment and 1 month after the end of treatment.

Other Outcomes (1)

• Changes in immune cells

  baseline,1,3,6,9,12 months after treatment and 1 month after the end of treatment.

Study Arms (4)

Cohort A：Patients with PBC were treated with sulfasalazine

EXPERIMENTAL

PBC treatment group: 1. PBC patients with poor response to UDCA after treatment: 30 patients continued to take UDCA 13-15mg/kg , 30 patients took UDCA 13-15mg/kg +SASP (0.5g orally three times a day), 30 patients took SASP (0.5g orally three times a day) for 12 months of follow-up observation. During 12 months of treatment, at the time of enrollment and the 1st/3rd/6th/9th/12th months, the liver function, fecal flora, liver fibrosis and immune related indexes were detected. 2. Newly treated PBC patients: 30 patients took UDCA 13-15mg/kg and 30 patients took UDCA 13-15mg/kg +SASP (0.5g orally three times a day) for 12 months of follow-up observation. During 12 months of treatment, at the time of enrollment and the 1st/3rd/6th/9th/12th months, the liver function, fecal flora, liver fibrosis and immune related indexes were detected.

Drug: Sulfasalazine enteric-coated tablets

Cohort B：Patients with HBV were treated with sulfasalazine

EXPERIMENTAL

Cohort B: 60 cases with hepatitis B cirrhosis were collected , 30 cases continued the current treatment(people with hepatitis B cirrhosis continue to take antivirals), and 30 patients were taking sulfasalazine for 12 months of follow-up observation. During 12 months of treatment, at the time of enrollment and the 1st/3rd/6th/9th/12th months, the liver function, fecal flora, liver fibrosis and immune related indexes were detected.

Drug: Sulfasalazine enteric-coated tablets

Cohort C：Patients with HCV were treated with sulfasalazine

EXPERIMENTAL

Cohort C: 60 cases with hepatitis C cirrhosis were collected，30 cases continued the current treatment(people with hepatitis C cirrhosis continue to take antivirals), and30 patients were taking sulfasalazine for 12 months of follow-up observation. During 12 months of treatment, at the time of enrollment and the 1st/3rd/6th/9th/12th months, the liver function, fecal flora, liver fibrosis and immune related indexes were detected.

Drug: Sulfasalazine enteric-coated tablets

Cohort D：Patients with alcoholic liver fibrosis/cirrhosis were treated with sulfasalazine

EXPERIMENTAL

60 cases with alcoholic cirrhosis were collected , 30 cases continued the current treatment and 30 patients were taking sulfasalazine for 12 months of follow-up observation. During 12 months of treatment at the time of enrollment and the 1st/3rd/6th/9th/12th months, the liver function, fecal flora, liver fibrosis and immune related indexes were detected.

Drug: Sulfasalazine enteric-coated tablets

Interventions

Sulfasalazine enteric-coated tablets DRUG

Sulfasalazine enteric-coated tablets Cohort A: PBC treatment group: (1) PBC patients with poor response to UDCA after treatment: 30 patients continued to take UDCA(13-15mg/kg), 30 patients took UDCA(13-15mg/kg)+SASP (0.5g orally three times a day), 30 patients took SASP (0.5g orally three times a day) for 12 months of follow-up observation. During 12 months of treatment, at the time of enrollment and the 1st/3rd/6th/9th/12th months, the liver function, fecal flora, liver fibrosis and immune related indexes were detected. (2) Newly treated PBC patients: 30 patients took UDCA(13- 15mg/kg) and 30 patients took UDCA(13-15mg/kg)+SASP (0.5g orally three times a day) for 12 months of follow-up observation. During 12 months of treatment, at the time of enrollment and the 1st/3rd/6th/9th/12th months, the liver function, fecal flora, liver fibrosis and immune related indexes were detected.

Cohort A：Patients with PBC were treated with sulfasalazine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign the informed consent form before the trial and be able to complete the study in accordance with the requirements of the trial protocol;
• The age is 18\~70 years old (including boundary value), the weight of male subjects is not less than 45 kg, and the weight of female subjects is not less than 40 kg. Body mass index (BMI) in the range of 18\~32kg/m2 (including critical value);
• Enrolled patients also need to meet:
• A:Patients with PBC cirrhosis PBC patients who have been treated and show an inadequate response to UDCA：(1) according to the biochemical response criteria for 2021 PBC, Enrolled patients need to meet the criteria of ALP ≥1.67 × ULN as a poor biochemical response to UDCA after 12 months of UDCA treatment; (2) meeting the diagnostic criteria for primary cholangitis (PBC) , i.e. meeting at least two of the following criteria: 1.indicators of cholestasis such as elevated Alkaline phosphatase; 2.Anti-mitochondrial antibody AMA or AMA-m2 positive, or if AMA negative, PBC-specific antibodies (anti-GP210 Andor anti-SP100) positive .3 liver biopsy consistent with PBC; Patients with newly diagnosed primary cholangitis (PBC-RRB- met the diagnostic criteria of at least two of the following): 1.indicators of cholestasis such as elevated Alkaline phosphatase; 2.Anti-mitochondrial antibody AMA or AMA-m2 positive, or if AMA negative, PBC-specific antibodies (anti-GP210 Andor anti-SP100) positive 3. liver biopsy consistent with PBC; B:Patients with hepatitis B cirrhosis Diagnosis of hepatitis B cirrhosis based on clinical history, histology or imaging.
• C:Patients with hepatitis C cirrhosis Diagnosis of hepatitis C cirrhosis based on clinical history, histology or imaging.
• D:Alcoholic hepatitis cirrhosis Diagnosis of alcoholic cirrhosis based on clinical history, histology, or imaging.

You may not qualify if:

• Those who have a history of allergies in the past, or the investigator suspects that they are allergic to the active ingredients of the drug or their excipients under study;
• Allergy to sulfasalazine and its metabolites, sulfonamides or salicylic acid;
• Patients with intestinal obstruction or urinary tract obstruction;
• Patients with porphyria, such as sulfonamides, have been reported to cause acute attacks.
• Acute and chronic liver disease with clinical significance caused by infections other than HBV, HCV, PBC, and alcoholic liver disease;
• Primary liver cancer; alpha-fetoprotein (AFP) greater than 50 ug/L or imaging suggests malignant liver mass; Those with other malignancies or a history of other malignancies in the 5 years prior to screening (except for complete remission of malignant tumors after treatment and no additional medical or surgical intervention within 3 years prior to screening);
• The investigator judged that there is impaired gastrointestinal function or gastrointestinal diseases that may affect the absorption of oral drugs, such as severe gastric ulcer, erosive gastritis, partial gastrectomy, and persistent \>Grade 2 gastrointestinal symptoms (e.g., nausea, vomiting, or diarrhoea);
• Serious diseases of circulatory, respiratory, urinary, blood, metabolic, immune, psychiatric, neurological, renal and other systems;
• Those who have had major trauma or undergone major surgery within 3 months before screening; or those who plan to undergo surgery during the study;
• Donated blood or lost blood ≥ 400mL within 3 months before screening, or received blood transfusion; or ≥ blood donation or blood loss within 1 month prior to screening 200mL；
• Those who are positive for AIDS antigen/antibody, positive for Treponema pallidum antibody and positive RPR test;
• History of drug dependence or drug abuse within 1 year prior to screening;
• Participate in clinical trials of other investigational drugs or medical devices within 3 months before screening, and take experimental drugs or use them Those who have medical devices;
• Those who have a positive pregnancy test during lactation or screening, or who have fertility requirements in the past two years;
• Subjects who the investigator believes have other factors that are not suitable to participate in this trial.

Sponsors & Collaborators

• The Second Affiliated Hospital of Chongqing Medical University: lead

Study Sites (2)

Chongqing Medical University

Chongqing, Chongqing Municipality, 400000, China

RECRUITING

Chongqing

Chongqing, Chongqing Municipality, 400000, China

RECRUITING

Related Publications (3)

• Gulamhusein AF, Hirschfield GM. Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol. 2020 Feb;17(2):93-110. doi: 10.1038/s41575-019-0226-7. Epub 2019 Dec 9.

  PMID: 31819247 RESULT

• Lv T, Chen S, Li M, Zhang D, Kong Y, Jia J. Regional variation and temporal trend of primary biliary cholangitis epidemiology: A systematic review and meta-analysis. J Gastroenterol Hepatol. 2021 Jun;36(6):1423-1434. doi: 10.1111/jgh.15329. Epub 2020 Dec 6.

  PMID: 33141955 RESULT

• Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2021 practice guidance update from the American Association for the Study of Liver Diseases. Hepatology. 2022 Apr;75(4):1012-1013. doi: 10.1002/hep.32117. Epub 2021 Dec 20. No abstract available.

  PMID: 34431119 RESULT

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mingli Peng, Doctor

  The Second Affiliated Hospital of Chongqing Medical University

  STUDY CHAIR

• Yinghua Lan, Doctor

  Doctor

  STUDY CHAIR

Central Study Contacts

Mingli Peng, Doctor

CONTACT

+8613512362906; 300618@cqmu.edu.cn

Yinghua Lan, Doctor

CONTACT

+8613796050629; 306346@hospital.cqmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: March 5, 2024
• Study Start: February 1, 2024
• Primary Completion (Estimated): October 10, 2028
• Study Completion (Estimated): October 10, 2028
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)