Boosting Biologics in UC

Boosting Biologics in Ulcerative Colitis

This study evaluates the safety of the probiotic compound IDOFORM TRAVEL® in patients with ulcerative colitis undergoing anti-TNF treatment with insufficient clinical response. Furthermore, the study aims to explore the composition of the bacteria of the gut as well as the immunological activity in patients with ulcerative colitis undergoing anti-TNF treatment, aiming to identify differences between groups of patients responding and not responding adequately to treatment.

The project will explore whether probiotics have beneficial effects as adjuvant therapy in ulcerative colitis patients with insufficient response to anti-TNF treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Bowel Diseases; Ulcerative Colitis
• Intervention / Treatment: Dietary supplement: IDOFORM®Travel

Detailed Description

The use of anti TNF agents has improved the medical treatment of ulcerative colitis (UC). However, one third of patients receiving such treatment will not reach remission. Studies have demonstrated that the gut microbiome influences the cytokine response and in particular the TNF production. In this study we aim to manipulate the gut microbiome in patients with ulcerative colitis not responding to anti-TNF therapy to evaluate potential beneficial effects.

20 UC patients with insufficient response to anti-tumor necrosis factor (anti-TNF) therapy upon routine evaluation colonoscopy 6-12 months after start of treatment will receive intervention with the probiotic formula IDOFORM Travel®, 4 capsules daily for 8 weeks. A colonoscopy will be performed at baseline (week 0) and after intervention (week8). Gut biopsies, fecal samples and serological markers will, in addition to clinical examination and endoscopic results, be used to evaluate the safety and possible beneficial effects of the intervention.

In a subsidiary cross-sectional study, 20 UC patients on anti-TNF therapy in remission upon evaluation colonoscopy will serve as controls. 20 individuals with no history of inflammatory bowel disease will be recruited as healthy controls.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jonas Lundekvam, MD; Phone Number: +47 45282558; Email: jonasalu@gmail.com

Study Locations

• Norway
  • Oslo, Norway
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Subjects may be included as cases in the study if they meet all of the following criteria:

• Diagnosed With ulcerative colitis based on Lennard-Jones criteria
• Under treatment With anti-TNF infusions/injections defined as infliximab or adalimumab
• Failure to Reach remission upon routine evaluation colonoscopy after 6-12 months of treatment - defined as an endoscopy sub score of ≥ using the Mayo score for ulcerative colitis
• Age 18-75
• Signed informed consent and expected Cooperation of the patients for the treatment and follow up must be obtained and documented according to International Committee on Harmonization (ICH) Good Clinical Practice (GCP), and national/local regulations.

Subjects may be included as Control subjects in the sub-study if they meet all of the following criteria:

• Diagnosed With ulcerative colitis based on Lennard-Jones Criteria
• Under treatment With anti-TNF infusions/injections defined as infliximab or adalimumab
• Remission upon routine colonoscopy after 6-12 months of treatment - defined as an endoscopy sub score of ≤ using the Mayo score for ulcerative colitis
• Age 18-75
• Signed informed consent and expected Cooperation of the patients for the treatment and follow up must be obtained and documented according to International Committee on Harmonization (ICH) Good Clinical Practice (GCP), and national/local regulations.

OR if they meet all the following criteria:

• No history of inflammatory bowel disease
• Age 18-75
• Signed informed consent and expected Cooperation of the patients for the treatment and follow up must be obtained and documented according to International Committee on Harmonization (ICH) Good Clinical Practice (GCP), and national/local regulations.

Exclusion Criteria:

• Clinical status poor to such extent that treating physician finds refraining from escalation of treatment contraindicated
• Signs of severe ulcerative colitis as defined by the "Montreal classification of severity of ulcerative colitis" = 3: Passage of at least six bloody stools daily, pulse rate of at least 90 beats per minute, temperature of at least 37.5°C, haemoglobin of less than 10.5 g/100 ml, and erythrocyte sedimentation rate (ESR) of at least 30 mm/h.
• Previous use of anti-TNF medication
• History of bowel resection, other inflammatory bowel disease (IBD)-related surgery, or other major intestinal surgery
• Plasma hepatitis C (HCV) positive
• Serum hepatitis B surface antigen (HBsAg) positive
• HIV positive
• Comorbidity of coeliac disease or malnutrition
• Pregnancy
• Concomitant use of non-steroid anti-inflammatory drugs (NSAIDS) or corticosteroids
• Concomitant use of antithrombotic pharmaceutical substances
• Regular (weekly) use of any probiotic substance within 3 months prior to inclusion
• Use of antibiotics within 3 months prior to inclusion
• Deranged liver function (serum albumin < 25 g/L or Child-Pugh ≥10)
• Renal failure (estimated glomerular filtration rate (eGFR) < 30
• Heart failure (NYHA class II-IV)
• Any reason why, in the opinion of the investigator, the patient should not participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention with probiotics; Intervention with the probiotic compound IDOFORM®Travel. The patient will receive four capsules orally every 24 hour (12*10^9 cfu/day) for eight weeks as adjuvant therapy to his/her anti-TNF treatment. The intervention arm will at the end of intervention serve as their own controls compared to baseline data (before intervention).	Dietary supplement: IDOFORM®Travel; Four capsules IDOFORM®Travel orally every 24 hour (12*10^9 cfu/day) for eight weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Unit of Measure: Frequency	8 weeks
Total Mayo Score for Ulcerative Colitis	Alterations in Total Mayo Score at time of control colonoscopy. Minimal value=0 (best outcome), Maximal value = 12 (worst outcome)	8 weeks
Change in Fecal Calprotectin	Change in Fecal Calprotectin from baseline (week 0) to end of intervention (week 8) and after intervention (week 12). Unit of measure: mg/kg	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alterations in mucosa-adherent microbial composition	Exploratory analyses of microbial composition at baseline (week 0) and at end of intervention (week 8). (Unit of Measure: Descriptive)	8 weeks
Alterations in epithelial gene expression	Exploratory (Unit of Measure: Descriptive)	8 weeks
Alterations in markers of chronic inflammation / immune activation	Explorative (Unit of Measure: Descriptive)	8 weeks

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Helse Sor-Ost
• Investigators: Principal Investigator: Asle Medhus, MD, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Estimated): December 15, 2023
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: January 22, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Ulcer; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 2016/2269

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No