Clinical trial NCT05387031: Efficacy of Ustekinumab Therapy in Patients With Symptomatic Stricturing Crohn's Disease
Official title: Efficacy of Ustekinumab-based Integrated Medicine Therapy in Patients With Symptomatic Stricturing Crohn's Disease: a Multicenter, Prospective, Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Crohn Disease
Stricture; Bowel
Intestinal Stricture
Keywords: Crohn Disease
intestinal stricture
Ustekinumab
integrated medicine therapy
cohort study
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Sixth Affiliated Hospital, Sun Yat-sen University
name: Second Affiliated Hospital of Soochow University
name: Chongqing Renji Hospital, University of Chinese Academy of Sciences
name: The First Affiliated Hospital of Zhejiang Chinese Medical University
name: Seventh Medical Center of PLA Army General Hospital
name: First People's Hospital of Hangzhou
name: Yangzhou University
name: Xian-Janssen Pharmaceutical Ltd.
First posted: 2022-05-24
Enrollment: 239
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants were adult CD patients treated with their first UST therapy for symptomatic strictures (confirmed on endoscopy or imaging) from centers of IBD at 8 hospitals all over China. This study does not involve the use of vulnerable groups.

Brief 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.

Detailed 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.

Eligibility criteria: 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
* Effective treatments for stricture in the past half a year, such as endoscopic balloon dilatation, intestinal stricture plasty, surgery/manual anal dilatation, etc.
* 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
* CT enterograph contraindications, such as allergy to contrast media
* Relative contraindications of biological agents, 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
* 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

Primary outcomes:
measure: Number of participants with treatment success at week 52
timeFrame: up to 52 weeks
Secondary outcomes:
measure: Number of participants with improvement in stricture inflammation and morphology on imaging
timeFrame: at week 8, 24, 52 and 104
measure: Number of participants with improvement in general health
timeFrame: at week 8, 24, 52 and 104
measure: Number of Participants with surgery
timeFrame: at week 8, 24, 52 and 104
measure: Number of participants with treatment success at week 104
timeFrame: at week 104
Other outcomes:
measure: Clinical response and clinical alleviate
timeFrame: at week 8, 24, 52 and 104
measure: Biochemical ease
timeFrame: at week 8, 24, 52 and 104
measure: UST drug concentration and antibody concentration
timeFrame: at week 8, 24, 52 and 104
measure: Safety outcomes
timeFrame: at week 8, 24, 52 and 104
Locations:
city: Peking
country: China
facility: Department of Gastroenterology, Seventh Medical Center of PLA Army General Hospital
state: Beijing
city: Chongqing
country: China
facility: Department of Gastroenterology, Chongqing Renji Hospital, University of Chinese Academy of Sciences
state: Chongqing
city: Guangzhou
country: China
facility: Department of Gastroenterology, Sixth Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Huai'an
country: China
facility: Department of Gastroenterology, Huai'an First People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Department of Gastroenterology, Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Yangzhou
country: China
facility: Department of Gastroenterology, Affiliated Hospital of Yangzhou University
state: Jiangsu
city: Hangzhou
country: China
facility: Center of Inflammatory Bowel Disease, Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University
state: Zhejiang
Study officials:
affiliation: Center of IBD, the Second Affiliated Hospital, Zhejiang University School of Medicine
name: Yan Chen, MD.
role: STUDY_CHAIR
affiliation: Center of IBD, the Second Affiliated Hospital, Zhejiang University School of Medicine
name: Jingwen Liu, MD.
role: PRINCIPAL_INVESTIGATOR
References: