IBS - Irritable Bowel SyndromeNCT05475314
Effect of Postbiotic Product on Colonic Barriers in IBS
A study testing ReFerm(R) in people with IBS - Irritable Bowel Syndrome, run by Nordisk Rebalance A/S at 1 site in Sweden.
Trial summary
Impaired intestinal permeability and microbial dysbiosis are important pathophysiological mechanisms underlying irritable bowel syndrome (IBS). ReFerm®, also called Profermin®, is a postbiotic product of oat gruel fermented with Lactobacillus plantarum 299v. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- IBS - Irritable Bowel Syndrome
- What is being tested?
- ReFerm(R)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteSweden
- Study dates
- 1 Dec 2020to 30 Apr 2022
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed IBS-D or IBS-M according to Rome IV criteria
- Moderate to severe IBS according to IBS-SSS score (≥175p)
- Age 18-70 years
- Fluency in written and spoken Swedish language
Who cannot join
- Organic gastrointestinal disease
- Previous major gastrointestinal operation (apart from appendectomy and cholecystectomy)
- Psychiatric disease (bipolar disease, schizophrenia)
- NSAID intake less than 2 weeks prior to endoscopy
- Self-reported pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Postbiotic Fermented Oat Gruel May Have a Beneficial Effect on the Colonic Mucosal Barrier in Patients With Irritable Bowel Syndrome
Impaired intestinal permeability and microbial dysbiosis are important pathophysiological mechanisms underlying irritable bowel syndrome (IBS). ReFerm®, also called Profermin®, is a postbiotic product of oat gruel fermented with Lactobacillus plantarum 299v. In this experimental study, we investigated whether ReFerm® has a beneficial effect on the intestinal epithelial barrier function in patients with IBS.
Read the detailed description
A single-blinded, randomised experimental study was conducted. Potential participants were screened based on the inclusion and exclusion criteria during telephone interviews. As the patients were their own controls, self-reported allergy was not an exclusion criterion as long as both interventions were carried out during unchanged allergic exposure.
Patients were then randomly allocated to one of two study arms: Referm® or thickened water (Thick-it ®, commercially available; Kent Precision Foods Group, Inc., Muscatine, IA, USA) as placebo. The patients underwent sigmoidoscopy with biopsies obtained from the distal colon at baseline and after 14 days of intervention with ReFerm® or placebo enema twice a day. The enema was administered rectally, in the left side position, and retained for as long as possible (at least 10 min) both in the left-sided and supine body position to activate retrograde peristalsis. To assess clinical improvement of symptoms, questionnaires were completed twice: before and after the intervention. During the 14 days of the intervention, the patients completed daily questionnaires. To improve compliance with the study intervention, the patients were given a check-up call by a principal investigator (OBe) twice per week during the intervention period.
- Conditions
- IBS - Irritable Bowel Syndrome
- Being tested
- ReFerm(R)
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ReFerm(R)Dietary supplement
Also called Profermin(R)
Enemas of approx 250 mL twice daily
| Study group | Role | What they receive |
|---|---|---|
| ReFerm(R); fermented oat gruel | Experimental | ReFerm® is manufactured by the fermentation of an oat gruel with L. plantarum 299v. The product is tested for pH and colony-forming units (CFU) of Enterobacteriaceae, yeasts/moulds, and L. plantarum 299v. The pH must be < 4.0, the CFU of Enterobacteriaceae and yeasts/moulds must be < 100/mL, and the CFU for L. plantarum 299v must be > 10E+08 immediately after completion of fermentation. The energy content of 100 mL ReFerm® is 58 kcal (240 kJ), from 1.6 g protein, 9.8 g carbohydrate, and 0.9 g fat. Each ReFerm® package contained 250 ml Receives: Dietary Supplement: ReFerm(R) |
| Thick-it(R); thickened water | Placebo comparator | Thick-it ® mildly thick, Kent Precision Foods Group, Inc.; commercially available) was chosen as a placebo to mimic the viscosity. This product contains artesian mineral water and ≤ 2% xanthan gum, calcium chloride, malic acid, potassium benzoate, potassium sorbate (to preserve freshness), sodium hexametaphosphate, and disodium EDTA. The energy content of 237 mL Thick-it ® (one package) was 5 kcal (21 kJ) from 0 g protein, 1 g carbohydrate, and 0 g fat Receives: Dietary Supplement: ReFerm(R) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intestinal permeability
Basic Science.
Mucosal permeability change (transcellular (amount of HRP (fmol/mL) and paracellular (amount of FITC (pM)), before and after treatment using an Ussing chamber with mounted patient biopsies
Measured: 14 days
Secondary outcomes (1)
Symptom change
Symptom change using the following questionnaires systems.
IBS severity scoring system for symptom change (significant if > 50 points) before and after treatment.
Gastrointestinal Symptom Rating Scale-IBS and Visceral sensitivity index. Data analyzed by cluster or as a total score for all items with statistically significant change.
Hospital Anxiety and Depression Scale. Cut-off values are indicated as ≥8 for subclinical (suspicious) anxiety or depression and ≥11 as definite cases on both the HADS-D and HADS-A, respectively.
Short Health Scale. Data analyzed by cluster or as a total score for all items with statistically significant change.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2022
- Study start1 Dec 2020
- Primary completion30 Apr 2021
- Study completion30 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for IBS - Irritable Bowel SyndromeStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients were randomly allocated to ReFerm® (18 patients, two men) or placebo (12 patients, three men) arms. There were no significant differences between the groups in terms of age, BMI, or disease severity.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nordisk Rebalance A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University Hospital, Linkoeping, Linkoeping University
- Responsible party
- Sponsor
- Investigators
- Susanna Walter, MD, Study chair, University Hospital, Linköping, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05475314
- Sponsor's protocol ID
- referm-barrier
- Status last verified
- Jul 2022
- First submitted
- 21 Jul 2022
- Last updated
- 26 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Biskou O, Walter S, Israelsen H, Winberg ME, Bednarska O, Keita AV. ReFerm(R): a postbiotic fermented oat gruel composition is reducing mast cell degranulation in the colon of patients with irritable bowel syndrome. Front Med (Lausanne). 2024 Jul 4;11:1408623. doi: 10.3389/fmed.2024.1408623. eCollection 2024.
PubMed 39026547Bednarska O, Biskou O, Israelsen H, Winberg ME, Walter S, Keita AV. A postbiotic fermented oat gruel may have a beneficial effect on the colonic mucosal barrier in patients with irritable bowel syndrome. Front Nutr. 2022 Dec 8;9:1004084. doi: 10.3389/fnut.2022.1004084. eCollection 2022.
PubMed 36570171
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Postbiotic Fermented Oat Gruel May Have a Beneficial Effect on the Colonic Mucosal Barrier in Patients With Irritable Bowel Syndrome
- ClinicalTrials.gov ID
- NCT05475314
- Acronym / sponsor ID
- referm-barrier
- Conditions
- IBS - Irritable Bowel Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Nordisk Rebalance A/SIndustry (pharma, biotech, devices)
- Collaborators
- University Hospital, Linkoeping, Linkoeping University
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 30 Apr 2022 (actual)
- First posted
- 26 Jul 2022 (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.
Impaired intestinal permeability and microbial dysbiosis are important pathophysiological mechanisms underlying irritable bowel syndrome (IBS). ReFerm®, also called Profermin®, is a postbiotic product of oat gruel fermented with Lactobacillus plantarum 299v. In this experimental study, we investigated whether ReFerm® has a beneficial effect on the intestinal epithelial barrier function in patients with IBS.
Detailed description
A single-blinded, randomised experimental study was conducted. Potential participants were screened based on the inclusion and exclusion criteria during telephone interviews. As the patients were their own controls, self-reported allergy was not an exclusion criterion as long as both interventions were carried out during unchanged allergic exposure.
Patients were then randomly allocated to one of two study arms: Referm® or thickened water (Thick-it ®, commercially available; Kent Precision Foods Group, Inc., Muscatine, IA, USA) as placebo. The patients underwent sigmoidoscopy with biopsies obtained from the distal colon at baseline and after 14 days of intervention with ReFerm® or placebo enema twice a day. The enema was administered rectally, in the left side position, and retained for as long as possible (at least 10 min) both in the left-sided and supine body position to activate retrograde peristalsis. To assess clinical improvement of symptoms, questionnaires were completed twice: before and after the intervention. During the 14 days of the intervention, the patients completed daily questionnaires. To improve compliance with the study intervention, the patients were given a check-up call by a principal investigator (OBe) twice per week during the intervention period.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Patients were randomly allocated to ReFerm® (18 patients, two men) or placebo (12 patients, three men) arms. There were no significant differences between the groups in terms of age, BMI, or disease severity.
| Arm | Type | Receives |
|---|---|---|
| ReFerm(R); fermented oat gruel | Experimental | Dietary Supplement: ReFerm(R)ReFerm® is manufactured by the fermentation of an oat gruel with L. plantarum 299v. The product is tested for pH and colony-forming units (CFU) of Enterobacteriaceae, yeasts/moulds, and L. plantarum 299v. The pH must be < 4.0, the CFU of Enterobacteriaceae and yeasts/moulds must be < 100/mL, and the CFU for L. plantarum 299v must be > 10E+08 immediately after completion of fermentation. The energy content of 100 mL ReFerm® is 58 kcal (240 kJ), from 1.6 g protein, 9.8 g carbohydrate, and 0.9 g fat. Each ReFerm® package contained 250 ml |
| Thick-it(R); thickened water | Placebo comparator | Dietary Supplement: ReFerm(R)Thick-it ® mildly thick, Kent Precision Foods Group, Inc.; commercially available) was chosen as a placebo to mimic the viscosity. This product contains artesian mineral water and ≤ 2% xanthan gum, calcium chloride, malic acid, potassium benzoate, potassium sorbate (to preserve freshness), sodium hexametaphosphate, and disodium EDTA. The energy content of 237 mL Thick-it ® (one package) was 5 kcal (21 kJ) from 0 g protein, 1 g carbohydrate, and 0 g fat |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Confirmed IBS-D or IBS-M according to Rome IV criteria
- Moderate to severe IBS according to IBS-SSS score (≥175p)
- Age 18-70 years
- Fluency in written and spoken Swedish language
Key exclusion criteria (5 listed)
- Organic gastrointestinal disease
- Previous major gastrointestinal operation (apart from appendectomy and cholecystectomy)
- Psychiatric disease (bipolar disease, schizophrenia)
- NSAID intake less than 2 weeks prior to endoscopy
- Self-reported pregnancy
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 |
|---|---|---|
| ReFerm(R)Also: Profermin(R)Enemas of approx 250 mL twice daily | Dietary supplement | ReFerm(R); fermented oat gruel, Thick-it(R); thickened water |
Primary outcome
Intestinal permeability
Time frame: 14 days
Basic Science. Mucosal permeability change (transcellular (amount of HRP (fmol/mL) and paracellular (amount of FITC (pM)), before and after treatment using an Ussing chamber with mounted patient biopsies
1 secondary outcome
Symptom change
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Derived from this study: PubMed 39026547Biskou O, Walter S, Israelsen H, Winberg ME, Bednarska O, Keita AV. ReFerm(R): a postbiotic fermented oat gruel composition is reducing mast cell degranulation in the colon of patients with irritable bowel syndrome. Front Med (Lausanne). 2024 Jul 4;11:1408623. doi: 10.3389/fmed.2024.1408623. eCollection 2024.
- Derived from this study: PubMed 36570171Bednarska O, Biskou O, Israelsen H, Winberg ME, Walter S, Keita AV. A postbiotic fermented oat gruel may have a beneficial effect on the colonic mucosal barrier in patients with irritable bowel syndrome. Front Nutr. 2022 Dec 8;9:1004084. doi: 10.3389/fnut.2022.1004084. eCollection 2022.
- 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.
Susanna Walter, MD study chair
University Hospital, Linköping, Sweden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ReFerm(R) in people with IBS - Irritable Bowel Syndrome, run by Nordisk Rebalance A/S 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 4 inclusion and 5 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: finished, as of the sponsor's last update on 26 Jul 2022. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Intestinal permeability (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05475314, which also lists 2 linked publications.
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 26 Jul 2022.