Clinical trial NCT06504784: The Role of Gut Bacteria in the Immune Response to Vaccination in Patients With Ulcerative Colitis
Official title: Effect of Dietary Fiber on Gut Microbiota Composition and Immune Response to Influenza Vaccination in Ulcerative Colitis Patients on Immunosuppressive Therapy: A Randomized, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Ulcerative Colitis
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
Collaborators: name: Calmino group AB
First posted: 2024-07-17
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: Patients with the inflammatory bowel disease ulcerative colitis (UC) are a high-risk group encouraged to get vaccinated against seasonal influenza. It is also known that UC patients may have an altered gut microbiota.

Patients with more severe disease are treated with immunosuppressive medications such as thiopurines and biologics that block pro-inflammatory cytokines. However, these treatments makes patients more susceptible to infections and results in a poorer response to certain types of vaccinations, as the immunosuppressive treatment aims to suppress mechanisms in the immune response.

The purpose of the study is to determine if dietary fibers can improve the immune response to influenza vaccination in UC patients treated with immunosuppressive medications. Further, the study aims to determine if dietary fibers (prebiotics) can enrich the composition and function of the gut microbiota in UC patients.

Detailed description: Project Description:

The purpose of the study is to determine if dietary fibers can improve the immune response to influenza vaccination in UC patients treated with immunosuppressive medications. The investigators also intend to determine if dietary fibers (prebiotics) can enrich the composition and function of the gut microbiota in UC patients.

Background and Justification:

Patients with moderate to severe UC often require lifelong medical treatment. Long-term treatment typically includes medications such as 5-ASA, immunomodulatory agents like thiopurines, and/or antibodies or biologics that block pro-inflammatory cytokines. These medical treatments aim to suppress the patient's inflammatory activity both systemically and locally in the gut. The treatment is often effective, leading to complete or partial healing of gut inflammation, known as remission. Unfortunately, the treatment also makes patients more susceptible to infections and results in a poorer response to certain types of vaccinations.

Patients with UC are a high-risk group and are encouraged to vaccinate against the seasonal influenza virus. Vaccination activates immune cells to produce antibodies that protect against the influenza virus. The effectiveness of the vaccination is measured by the levels (titers) of influenza-specific antibodies formed. Previous studies have shown that patients treated with biologics such as antibodies against the pro-inflammatory cytokine TNF, have a poorer response to various vaccinations, including influenza, and therefore receive less protection against the infection.

Recent studies have shown that the composition of the gut microbiota at the time of vaccination affects the response/protection from vaccination in healthy volunteers. The studies also implicate research subjects with a "poorer"/more depleted composition of gut bacteria with a reduced ability to form antibodies and thus create immunological protection in response to vaccination. It is known that UC patients have a depleted composition of gut bacteria compared to healthy individuals.

Previous studies have suggested that it may be possible to improve the composition of gut bacteria in UC patients by enriching the diet with dietary fibers, known as prebiotics, which promote the presence of certain gut bacteria believed to have health-promoting effects. There are many different types of dietary fibers consisting of carbohydrates and starch. Examples of dietary fibers include inulin, mannose, galacto-oligosaccharides, and starch.

Study Design:

Recruitment of Participants:

UC Patients: Patients treated at the Gastroenterology Clinic, Sahlgrenska University Hospital, will be invited via mail and follow-up phone calls. This study aims to recruit 100 patients (18-65 years) on maintenance treatment with anti-TNF agents and/or thiopurines, or 5-ASA.

Healthy subjects: Recruited through local advertising at Sahlgrenska University Hospital and social media. This study aims to recruit 50 healthy participants as control (18-65 years).

All research subject will be informed and asked verbally to participate in the study. Those who agree will sign informed consent.

Intervention:

All study participants will be randomized to receive either 10 g of dietary fiber per day (divided into 2 doses) or 10 g of placebo (glucose, divided into 2 doses) for 3 weeks before the influenza vaccination. They will continue to take dietary fiber or placebo for 3-4 weeks after the vaccination.

The dietary fiber mix (total 10 g/day) includes inulin, acetylated polymannose, galacto-oligosaccharides, and resistant starch. Intervention products were provided by Calmino group AB, Sweden.

All research subjects will be vaccinated after 3 weeks of intervention period. The vaccination procedure and dosage will be the same as in standard clinical practice.

All participants will complete questionnaires to assess GI symptom severity, and blood and fecal samples will be collected at baseline, 3 weeks after intervention (vaccination visit), 6 weeks after intervention/end of intervention (3 weeks post-vaccination) and at long term follow-up ( 20-25 weeks post-vaccination).

Significance:

This is the first time the impact of dietary fibers on vaccination response is being studied in UC patients treated with anti-inflammatory drugs. If the study shows favorable results, it could lead to changes in clinical practice, including advising patients to intake dietary fiber to enrich gut flora, improve immune response, and enhance protection during vaccination.

Eligibility criteria: Inclusion Criteria:

* UC patients, aged 18-65, in remission, with stable maintenance treatment for at least 6 months consisting of anti-TNF medications and/or thiopurines, or 5-ASA.
* Healthy volunteers, aged 18-65.

Exclusion Criteria:

* Comorbidity according to the Charlston Comorbidity Index
* Ongoing immunosuppressive treatment for a condition other than inflammatory bowel disease
* Colorectal surgical treatment for inflammatory bowel disease
* Treatment with antibiotics in the past 3 months
* Intake of probiotic or prebiotic dietary supplements in the past 3 months
* Inability to understand information about the study or provide informed consent

Additional Exclusion Criteria for Healthy Volunteers:

-Inflammatory bowel disease or suspicion thereof

Primary outcomes:
measure: The level of influenza-specific antibodies (titers) in blood samples measured post-vaccination.
timeFrame: Measured at Visit 2 (day of vaccination), Visit 3 (3-4 weeks post-vaccination), and Visit 4 (20-25 weeks post-vaccination).
measure: Effect of Dietary Fibers on Gastrointestinal Symptoms using the validated Gastrointestinal Symptom Rating Scale (GSRS) questionnaire in Patients with Ulcerative Colitis comparing baseline vs. end of 6 week oral intervention with dietary fiber.
timeFrame: GI symptoms using GSRS symptom questionnaire were assessed at baseline and at 3 week and 6 weeks after intervention
measure: Effect of Dietary Fibers on disease activity assessed using a modified Mayo score form in Patients with Ulcerative Colitis comparing baseline vs. end of 6 week oral intervention.
timeFrame: Mayo score (modified) will be measured at baseline and at 3 week and 6 weeks after intervention
Secondary outcomes:
measure: Effect of dietary fiber intake on metabolite composition in UC patients and healthy controls comparing baseline vs. end of 6 week oral intervention.
timeFrame: Analyzed from fecal samples collected at Visit 1 (baseline), Visit 2 (day of vaccination), Visit 3 (3-4 weeks post-vaccination), and Visit 4 (20-25 weeks post-vaccination).]
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
References: