Efficacy of Ustekinumab-based Integrated Medicine Therapy in Patients With Symptomatic Stricturing Crohn's Disease

Crohn Disease Clinical Trial

Official title:

Efficacy of Ustekinumab-based Integrated Medicine Therapy in Patients With Symptomatic Stricturing Crohn's Disease: a Multicentre, Prospective, Observational Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05387031
• Other study ID #: 2022-0276
• Status: Recruiting
• Start date: May 26, 2022
• Est. completion date: June 2025

Study information

• Verified date: May 2022
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Yan Chen, MD.
• Phone: +86-571-87783777
• Email: chenyan72_72[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study intends to select patients with confirmed moderate-to-severe Crohn's disease (CD) and obstructive symptoms of intestinal stenosis, who have clear evidence of lumen stenosis caused by the disease itself through radiography or endoscopy. After the informed consent of the patients, comprehensive drug therapy with ustekinumab as the mainstay was performed. The basic information and medical history of the patients were collected, and the treatment process of the patients was followed up and recorded, and the drug regimen was adjusted according to the physician's experience and judgment. At different follow-up time points, blood, feces, tissue and other specimens of patients were collected according to the situation, and gastrointestinal endoscopy, imaging examination, laboratory index examination, self-assessment of subjects' symptoms, and nutritional risk screening were performed on the patients. This study evaluated the CD disease activity, obstructive symptoms, and radiographic or endoscopic remission in patients at different follow-up time points, and comprehensively evaluated the efficacy of ustekinumab in relieving stenotic CD and its related factors.

Description:

This study intends to select patients with confirmed moderate-to-severe CD and obstructive symptoms of intestinal stenosis, who have clear evidence of lumen stenosis caused by the disease itself through radiography or endoscopy. After the informed consent of the patients, comprehensive drug therapy with ustekinumab as the mainstay was performed. The basic information and medical history of the patients were collected, and the treatment process of the patients was followed up and recorded, and the drug regimen was adjusted according to the physician's experience and judgment. At different follow-up time points, blood, feces, tissue and other specimens of patients were collected according to the situation, and gastrointestinal endoscopy, imaging examination, laboratory index examination, self-assessment of subjects' symptoms, and nutritional risk screening were performed on the patients. This study evaluated the CD disease activity, obstructive symptoms, and radiographic or endoscopic remission in patients at different follow-up time points, and comprehensively evaluated the efficacy of ustekinumab in relieving stenotic CD and its related factors.

The investigators conduct follow-up and disease assessment at weeks 0, 12, 24, 52, and 104, respectively. The investigators define the primary endpoint of the study as the treatment success of ustekinumab at week 52, and investigate the efficacy of ustekinumab by site of stricture and assessed possible clinical, biochemical, and radiological predictors of treatment response at weeks 12, 24, 52, and 104. This clinical study provides evidence for the efficacy of ustekinumab-based comprehensive drugs in the treatment of stenotic Crohn's disease, provides biological information resources for future treatment options for patients with stenotic CD, and can also be used for disease diagnosis and treatment. In this group of people, the investigators tend to further analyze and find the influencing factors related to the development of stenotic CD disease and drug response, in order to provide corresponding support for clinical activities in the early stage of the disease or during the treatment process, and to improve the effectiveness and accuracy of individualized treatment for patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of moderate to severe Crohn's disease

• Obstructive symptoms within the last eight weeks

• A single or several lumen stricture(s) identified by radiological imaging or endoscopy

• For strictures identified by CT enterograph defined as a lesion with combination of a reduction of luminal narrowing >50%, an increase in bowel wall thickness >25% relative to non-affected bowel and pre-stricture dilation >3.0 cm

• For strictures identified during endoscopic procedure defined by intestinal strictures with a lumen diameter =12 mm or even inability to pass the endoscope across the narrowing

Exclusion Criteria:

• Requirement of urgent surgery or endoscopic intervention within 2 months as judged by the clinician

• Symptoms or signs of perforation such as active perianal sepsis, abdominal abscess, intestinal fistula, and abdominal adhesions

• Intestinal obstruction caused by surgery, intra-abdominal abscess, isolated intestinal stricture

• Unable to eat after using enteral nutrition for more than 2 months

• History of ustekinumab (UST) or other IL-23 antagonists use in the past 12 months,

• Bowel ultrasound Limberg score of 1-2

• CT enterograph contraindications, such as pulmonary tuberculosis-positive chest X-ray or active tuberculosis with strong positive tuberculin skin test, myocardial infarction, heart failure, or demyelinating neurological disease in the past five years

• Currently suffering from a solid tumor, lymphoma, or melanoma and undergoing chemotherapy or radiation therapy

• Combination of intestinal dysplasia (eg, diagnosed with short bowel syndrome), colostomy, or colorectal tumors

• Combination of active gastrointestinal bleeding, shock, severe diarrhea, refractory vomiting and severe malabsorption syndrome

• Combination of severe liver and kidney dysfunction

• Coexistence of bacterial or viral active infection

• Pregnant or breastfeeding

• Severe hemodynamics, unstable vital signs or presence of rapidly progressive or end-stage disease, expected to be fatal during the course of the study

Related Conditions & MeSH terms

• Constriction, Pathologic
• Crohn Disease
• Intestinal Stricture
• Stricture; Bowel

Intervention

Drug:
• Ustekinumab
The initial intravenous (IV) infusion with ustekinumab at baseline was weight-adjusted (260 mg =55 kg, 390 mg between 55 and 85 kg, 520 mg =85 kg). According to the label, the first subcutaneous (SC) 90 mg induction dose was administered at week 8 followed by a maintenance dose of 90 mg SC every 8 or 12 weeks, at the discretion of the physician. This study evaluated the CD disease activity, obstructive symptoms, and radiographic or endoscopic remission in patients at different follow-up time points, and comprehensively evaluated the efficacy of ustekinumab in relieving stenotic CD and its related factors.

Locations

Country	Name	City	State
China	Center of Inflammatory Bowel Disease, Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang

Sponsors (4)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University	Chongqing Renji Hospital, University of Chinese Academy of Sciences, Second Affiliated Hospital of Soochow University, Sixth Affiliated Hospital, Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment success at week 52	The primary endpoint was the success at week 52, defined as ustekinumab continuation with all the following criteria: (1) no use of a prohibited treatment (corticosteroids after the eight week following inclusion, parenteral nutrition, other biological agents); (2) no endoscopic dilation; (3) no bowel surgery for resection of small bowel stricture; (4) no severe adverse events leading to ustekinumab withdrawal and (5) no study withdrawal whatever the reason.; Clinical improvement was measured by symptoms and clinical remission (Crohn's Disease Activity Index <150), steroid-free symptom improvement (obstructive symptom score) following initial steroid tapering, Crohn's Disease Obstructive Score (improvement of =1 point), treatment failure (defined as bowel obstruction requiring surgery, endoscopic balloon dilation, or persisting symptoms necessitating change in treatment), the need for surgery.	up to 52 weeks
Secondary	Number of participants with improvement in stricture inflammation and morphology on imaging	CT and MRI stricture improvement was defined as resolution of prestenotic dilatation (small bowel diameter <3.0 cm); stricture resolution (normal bowel wall thickness and luminal diameter with absence of prestenotic dilation; and reduced stricture length by =1 mm). Intestinal ultrasound stricture improvement included normalisation of prestenotic dilation (<3.0 cm) or reduction in prestenotic dilation (=50%). Endoscopic stricture improvement included increased luminal diameter; the ability to pass a standard paediatric colonoscope (11.5 mm diameter); and improved stricture ulceration score using the modified Simple Endoscopic Score for Crohn's Disease.	at week 8, 24, 52 and 104
Secondary	Number of participants with improvement in general health	General health improvement was measured by patient reported outcomes of Inflammatory Bowel Disease (IBD) Quality of Life Questionnaire. The minimum and maximum values are 32 and 224 points respectively, and higher scores mean a better outcome.	at week 8, 24, 52 and 104
Secondary	Number of Participants with surgery	Number of Participants with surgery during follow-up included patients undergoing any surgery for endoscopic dilatation and stricture resection.	at week 8, 24, 52 and 104