Ulcerative ColitisNCT06504784
The Role of Gut Bacteria in the Immune Response to Vaccination in Patients With Ulcerative Colitis
A study testing Dietary Fiber Mixture in people with Ulcerative Colitis, run by Sahlgrenska University Hospital at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Dietary Fiber Mixture
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteSweden
- Study dates
- 14 Sep 2023to Oct 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- Dietary Fiber Mixture, Placebo
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary Fiber MixtureDietary supplement
10g/day of dietary fibre mixture - a mixture of oligo-and polysaccharides
PlaceboOther
10g/day of placebo (glucose)
| Study group | Role | What they receive |
|---|---|---|
| Dietary Fibre Mixture | Experimental | Study participants receive 10g/day of dietary fibre mixture (a mixture of oligo-and polysaccharides), divided into two doses and administered orally for 6 weeks. Receives: Dietary Supplement: Dietary Fiber Mixture |
| Placebo | Placebo comparator | Study participants receive 10g/day of placebo (glucose) matching the fibre mixture in colour and flavor, divided into two doses and administered orally for 6 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The level of influenza-specific antibodies (titers) in blood samples measured post-vaccination.
The level of influenza-specific antibodies (titers) in blood samples of UC patients measured post-vaccination in intervention group (receiving dietary fiber) compared to patients in the placebo group.
Measured: Measured at Visit 2 (day of vaccination), Visit 3 (3-4 weeks post-vaccination), and Visit 4 (20-25 weeks post-vaccination).
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.
GI symptoms are assessed using the validated Gastrointestinal Symptom Rating Scale (GSRS). GSRS is a 15 item measure of IBS symptom severity. The scale measures the severity of each symptom on a scale from 1 to 7. Maximum total score is 7 and minimum score is 1, where a higher score indicates higher gastrointestinal symptom severity.
Measured: GI symptoms using GSRS symptom questionnaire were assessed at baseline and at 3 week and 6 weeks after intervention
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.
Disease activity is assessed using a modified Mayo score (UC patients only). Mayo score measures disease activity on a scale from to 6, where the maximum score is 6 and minimum score is 0, and higher score indicated worse outcome with regards to disease activity. Change in total Mayo score will be evaluated.
Measured: Mayo score (modified) will be measured at baseline and at 3 week and 6 weeks after intervention
Secondary outcomes (1)
Effect of dietary fiber intake on metabolite composition in UC patients and healthy controls comparing baseline vs. end of 6 week oral intervention.
Change in metabolite profile/composition in UC patients and healthy controls after intervention with dietary fiber compared to placebo will be established. Fecal samples will be used to evaluate the Metabolite profile using untargeted Liquid chromatography coupled to a mass spectrometer (LC-MS). Change in the metabolite profile measured as metabolite signal response from Baseline to 6 Weeks after intervention will be evaluated.
Measured: 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).]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2024
- Study start14 Sep 2023
- Primary completionJul 2024 (estimated)
- Study completionOct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by Sahlgrenska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, placebo-controlled study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Calmino group AB
- Responsible party
- Principal investigator, Jóhann P. Hreinsson, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06504784
- Sponsor's protocol ID
- PreVac2023
- Status last verified
- Jul 2024
- First submitted
- 11 Jun 2024
- Last updated
- 19 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06504784
- Acronym / sponsor ID
- PreVac2023
- Conditions
- Ulcerative Colitis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Collaborators
- Calmino group AB
- Study start
- 14 Sep 2023 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 17 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized, double-blind, placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| Dietary Fibre Mixture | Experimental | Dietary Supplement: Dietary Fiber MixtureStudy participants receive 10g/day of dietary fibre mixture (a mixture of oligo-and polysaccharides), divided into two doses and administered orally for 6 weeks. |
| Placebo | Placebo comparator | Other: PlaceboStudy participants receive 10g/day of placebo (glucose) matching the fibre mixture in colour and flavor, divided into two doses and administered orally for 6 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dietary Fiber Mixture10g/day of dietary fibre mixture - a mixture of oligo-and polysaccharides | Dietary supplement | Dietary Fibre Mixture |
| Placebo10g/day of placebo (glucose) | Other | Placebo |
Primary outcome
The level of influenza-specific antibodies (titers) in blood samples measured post-vaccination.
Time frame: Measured at Visit 2 (day of vaccination), Visit 3 (3-4 weeks post-vaccination), and Visit 4 (20-25 weeks post-vaccination).
The level of influenza-specific antibodies (titers) in blood samples of UC patients measured post-vaccination in intervention group (receiving dietary fiber) compared to patients in the placebo group.
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.
Time frame: GI symptoms using GSRS symptom questionnaire were assessed at baseline and at 3 week and 6 weeks after intervention
GI symptoms are assessed using the validated Gastrointestinal Symptom Rating Scale (GSRS). GSRS is a 15 item measure of IBS symptom severity. The scale measures the severity of each symptom on a scale from 1 to 7. Maximum total score is 7 and minimum score is 1, where a higher score indicates higher gastrointestinal symptom severity.
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.
Time frame: Mayo score (modified) will be measured at baseline and at 3 week and 6 weeks after intervention
Disease activity is assessed using a modified Mayo score (UC patients only). Mayo score measures disease activity on a scale from to 6, where the maximum score is 6 and minimum score is 0, and higher score indicated worse outcome with regards to disease activity. Change in total Mayo score will be evaluated.
1 secondary outcome
Effect of dietary fiber intake on metabolite composition in UC patients and healthy controls comparing baseline vs. end of 6 week oral intervention.
Time frame: 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).]
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary Fiber Mixture in people with Ulcerative Colitis, run by Sahlgrenska University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The level of influenza-specific antibodies (titers) in blood samples measured post-vaccination. (time frame: Measured at Visit 2 (day of vaccination), Visit 3 (3-4 weeks post-vaccination), and Visit 4 (20-25 weeks post-vaccination).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2024.