Celiac DiseasePhase 2NCT03271138
Bifidobacterium Infantis NLS Super Strain for Celiac Disease Patients on a Gluten-free Diet With Persistent Gastrointestinal Symptoms
A Phase 2 study testing Bifidobacterium infantis NLS super strain (Natren LIFE START®2) in people with Celiac Disease, run by Global Institute of Probiotics at 1 site in Argentina.
Trial summary
The primary purpose of this randomized, double-blinded, placebo-controlled, crossover clinical trial is to evaluate the efficacy of dietary supplementation with Bifidobacterium infantis NLS super strain among celiac disease patients on a gluten-free who have persistent gastrointestinal symptoms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Celiac Disease
- What is being tested?
- Bifidobacterium infantis NLS super strain (Natren LIFE START®2)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteArgentina
- Study dates
- 21 Jul 2017to 7 Dec 2017
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women at least 18 years of age
- Precise diagnosis of celiac disease: serology (a-tTG IgA and/or DGP IgG and/or EmA) and histology (Marsh IIIa or greater) concordantly positive, confirmed at investigator's institution
- Consuming a gluten-free diet for at least 2 years
- Persistent gastrointestinal symptoms: global GSRS questionnaires ≥2 or ≥ 3 points for any of the 5 sub-dimensions
- Signature of informed consent
Who cannot join
- Patients not interested or unable to comply with questionnaires and collection of samples of blood, feces, and urine
- Complicated celiac disease (refractory, ulcerative jejunoileitis, lymphoma)
- Concomitant pathologies that are uncompensated or untreated (Type I or II diabetes mellitus, hyperthyroidism, hypothyroidism, diarrhea due to bile salts, pancreatic insufficiency, bacterial overgrowth)
- Consumption within the 2 weeks prior to study enrollment of medication that interferes with bowel functioning (antibiotics, NSAIDs, laxatives, metformin, opiates, anticholinergics [atropine, antidepressants, neuroleptics, antipsychotics, antiparkinsonians], anticonvulsants, antihistamines, antihypertensives [calcium antagonists, clonidine, diuretics, metal ions (aluminum), antacids, sucralfate, barium sulfate, bismuth, calcium, iron, heavy metals (arsenic, lead, mercury)], resins (cholestyramine), or any other medication deemed relevant by the investigator).
- Women that are pregnant or may become pregnant during the study
Trial locations and contacts
1 site in 1 country.
Argentina1 site
Small Bowel Section, Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital
Buenos Aires
About this study
Official title: A Randomized Controlled Trial of Dietary Supplementation With Bifidobacterium Infantis NLS Super Strain Among Celiac Disease Patients on a Gluten-free Diet With Persistent Gastrointestinal Symptoms
The primary purpose of this randomized, double-blinded, placebo-controlled, crossover clinical trial is to evaluate the efficacy of dietary supplementation with Bifidobacterium infantis NLS super strain among celiac disease patients on a gluten-free who have persistent gastrointestinal symptoms.
Read the detailed description
Most patients with celiac disease demonstrate substantial clinical improvement during the first few weeks after the onset of the consumption of a gluten-free diet. However, between 30-50% of patients with celiac disease have persistent gastrointestinal symptoms despite consuming a gluten-free diet and presenting negative antibodies. It has recently been reported that celiac disease patients treated with a gluten-free diet that still have persistent symptoms possess different intestinal microbiota patterns than patients without persistent symptoms. Furthermore, a pilot study showed that dietary supplementation with probiotics (Bifidobacterium infantis NLS super strain - Natren LIFESTART®) in untreated celiac disease patients was associated with a significant improvement in symptoms as compared to placebo. Collectively, these findings contribute to the hypothesis that celiac disease patients on a gluten-free diet in whom gastrointestinal symptoms persist may benefit from the supplementation of Bifidobacterium infantis NLS super strain.
Participants in this double-blinded crossover trial will be randomized to receive either placebo or Bifidobacterium infantis NLS super strain for 3 weeks, followed by a 2 week washout period, and then followed by 3 weeks of the other of either placebo or probiotic supplementation.
- Conditions
- Celiac Disease
- Being tested
- Bifidobacterium infantis NLS super strain (Natren LIFE START®2), Placebo
- Keywords
- Celiac Disease, Gluten-Free Diet, Bifidobacterium infantis NLS super strain, gastrointestinal symptoms, quality of life, microbiota, IgA TTG, IgA DGP
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bifidobacterium infantis NLS super strain (Natren LIFE START®2)Dietary supplement
2 capsules, 3 times per day, for daily total of 12x10^9 CFU Bifidobacterium infantis NLS super strain
PlaceboOther
2 capsules, 3 times per day, containing rice flour, hydroxypropyl and methylcellulose
| Study group | Role | What they receive |
|---|---|---|
| Bifidobacterium Infantis NLS Super Strain | Active comparator | Participants in the probiotic period will take two capsules of Bifidobacterium infantis NLS super strain (Natren LIFE START®2) three times per day for three weeks. Each capsule contains 2 x 10^9 colony-forming units (CFU) of Bifidobacterium infantis NLS super strain, for a total daily dose of 12 X 10^9 CFU. The probiotic will be kept refrigerated during transportation and throughout the study period. Receives: Dietary Supplement: Bifidobacterium infantis NLS super strain (Natren LIFE START®2) |
| Placebo | Placebo comparator | Participants in the placebo period will take two capsules of placebo three times per day for three weeks. The placebo capsules contain rice flour, hydroxypropyl and methylcellulose. The placebo will be kept refrigerated during transportation and throughout the study period. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Gastrointestinal Symptom Rating Scale (GSRS)
Measured: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Secondary outcomes (6)
Changes in Celiac Symptoms Index (CSI)
Measured: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in Quality of Life: SF-36
Measured: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in gut microbiota
16S rRNA Illumina based sequencing
Measured: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in Gluten Immunogenic Peptides (GIP)
Measured: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in serology (IgA tTG & IgA DGP)
Measured: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in anthropometric measurements (BMI)
Measured: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2017
- Study start21 Jul 2017
- Primary completion7 Dec 2017
- Study completion7 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Celiac DiseaseStudies 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 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Institute of Probiotics
- Sponsor type
- University, hospital or other
- Collaborators
- Dr. C. Bonorino Udaondo Gastroenterology Hospital, Research Institute, Universidad del Salvador, Consejo de Investigaciones en Salud, Ministerio de Salud, Gobierno Autónomo de Buenos Aires
- Responsible party
- Sponsor
- Investigators
- Edgardo Smecuol, MD, Principal investigator, Dr. C. Bonorino Udaondo Gastroenterology HospitalJulio C Bai, MD, Study director, Dr. C. Bonorino Udaondo Gastroenterology Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03271138
- Sponsor's protocol ID
- GlobalIP
- Other IDs
- 001
- Status last verified
- Aug 2018
- First submitted
- 30 Aug 2017
- Last updated
- 24 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Smecuol E, Constante M, Temprano MP, Costa AF, Moreno ML, Pinto-Sanchez MI, Vazquez H, Stefanolo JP, Gonzalez AF, D'Adamo CR, Niveloni SI, Maurino E, Verdu EF, Bai JC. Effect of Bifidobacterium infantis NLS super strain in symptomatic coeliac disease patients on long-term gluten-free diet - an exploratory study. Benef Microbes. 2020 Oct 12;11(6):527-534. doi: 10.3920/BM2020.0016. Epub 2020 Oct 9.
PubMed 33032471
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Dietary Supplementation With Bifidobacterium Infantis NLS Super Strain Among Celiac Disease Patients on a Gluten-free Diet With Persistent Gastrointestinal Symptoms
- ClinicalTrials.gov ID
- NCT03271138
- Acronym / sponsor ID
- GlobalIP
- Conditions
- Celiac Disease
- Keywords
- Celiac Disease, Gluten-Free Diet, Bifidobacterium infantis NLS super strain, gastrointestinal symptoms, quality of life, microbiota, IgA TTG, IgA DGP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Global Institute of ProbioticsUniversity, hospital or other
- Collaborators
- Dr. C. Bonorino Udaondo Gastroenterology Hospital, Research Institute, Universidad del Salvador, Consejo de Investigaciones en Salud, Ministerio de Salud, Gobierno Autónomo de Buenos Aires
- Study start
- 21 Jul 2017 (actual)
- Primary completion
- 7 Dec 2017 (actual)
- Study completion
- 7 Dec 2017 (actual)
- First posted
- 1 Sep 2017 (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.
The primary purpose of this randomized, double-blinded, placebo-controlled, crossover clinical trial is to evaluate the efficacy of dietary supplementation with Bifidobacterium infantis NLS super strain among celiac disease patients on a gluten-free who have persistent gastrointestinal symptoms.
Detailed description
Most patients with celiac disease demonstrate substantial clinical improvement during the first few weeks after the onset of the consumption of a gluten-free diet. However, between 30-50% of patients with celiac disease have persistent gastrointestinal symptoms despite consuming a gluten-free diet and presenting negative antibodies. It has recently been reported that celiac disease patients treated with a gluten-free diet that still have persistent symptoms possess different intestinal microbiota patterns than patients without persistent symptoms. Furthermore, a pilot study showed that dietary supplementation with probiotics (Bifidobacterium infantis NLS super strain - Natren LIFESTART®) in untreated celiac disease patients was associated with a significant improvement in symptoms as compared to placebo. Collectively, these findings contribute to the hypothesis that celiac disease patients on a gluten-free diet in whom gastrointestinal symptoms persist may benefit from the supplementation of Bifidobacterium infantis NLS super strain.
Participants in this double-blinded crossover trial will be randomized to receive either placebo or Bifidobacterium infantis NLS super strain for 3 weeks, followed by a 2 week washout period, and then followed by 3 weeks of the other of either placebo or probiotic supplementation.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bifidobacterium Infantis NLS Super Strain | Active comparator | Dietary Supplement: Bifidobacterium infantis NLS super strain (Natren LIFE START®2)Participants in the probiotic period will take two capsules of Bifidobacterium infantis NLS super strain (Natren LIFE START®2) three times per day for three weeks. Each capsule contains 2 x 10^9 colony-forming units (CFU) of Bifidobacterium infantis NLS super strain, for a total daily dose of 12 X 10^9 CFU. The probiotic will be kept refrigerated during transportation and throughout the study period. |
| Placebo | Placebo comparator | Other: PlaceboParticipants in the placebo period will take two capsules of placebo three times per day for three weeks. The placebo capsules contain rice flour, hydroxypropyl and methylcellulose. The placebo will be kept refrigerated during transportation and throughout the study period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men or women at least 18 years of age
- Precise diagnosis of celiac disease: serology (a-tTG IgA and/or DGP IgG and/or EmA) and histology (Marsh IIIa or greater) concordantly positive, confirmed at investigator's institution
- Consuming a gluten-free diet for at least 2 years
- Persistent gastrointestinal symptoms: global GSRS questionnaires ≥2 or ≥ 3 points for any of the 5 sub-dimensions
- Signature of informed consent
Key exclusion criteria (5 listed)
- Patients not interested or unable to comply with questionnaires and collection of samples of blood, feces, and urine
- Complicated celiac disease (refractory, ulcerative jejunoileitis, lymphoma)
- Concomitant pathologies that are uncompensated or untreated (Type I or II diabetes mellitus, hyperthyroidism, hypothyroidism, diarrhea due to bile salts, pancreatic insufficiency, bacterial overgrowth)
- Consumption within the 2 weeks prior to study enrollment of medication that interferes with bowel functioning (antibiotics, NSAIDs, laxatives, metformin, opiates, anticholinergics [atropine, antidepressants, neuroleptics, antipsychotics, antiparkinsonians], anticonvulsants, antihistamines, antihypertensives [calcium antagonists, clonidine, diuretics, metal ions (aluminum), antacids, sucralfate, barium sulfate, bismuth, calcium, iron, heavy metals (arsenic, lead, mercury)], resins (cholestyramine), or any other medication deemed relevant by the investigator).
- Women that are pregnant or may become pregnant during the study
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 |
|---|---|---|
| Bifidobacterium infantis NLS super strain (Natren LIFE START®2)2 capsules, 3 times per day, for daily total of 12x10^9 CFU Bifidobacterium infantis NLS super strain | Dietary supplement | Bifidobacterium Infantis NLS Super Strain |
| Placebo2 capsules, 3 times per day, containing rice flour, hydroxypropyl and methylcellulose | Other | Placebo |
Primary outcome
Changes in Gastrointestinal Symptom Rating Scale (GSRS)
Time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
6 secondary outcomes
Changes in Celiac Symptoms Index (CSI)
Time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in Quality of Life: SF-36
Time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in gut microbiota
Time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in Gluten Immunogenic Peptides (GIP)
Time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in serology (IgA tTG & IgA DGP)
Time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
Changes in anthropometric measurements (BMI)
Time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
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 24 Aug 2018.
- Derived from this study: PubMed 33032471Smecuol E, Constante M, Temprano MP, Costa AF, Moreno ML, Pinto-Sanchez MI, Vazquez H, Stefanolo JP, Gonzalez AF, D'Adamo CR, Niveloni SI, Maurino E, Verdu EF, Bai JC. Effect of Bifidobacterium infantis NLS super strain in symptomatic coeliac disease patients on long-term gluten-free diet - an exploratory study. Benef Microbes. 2020 Oct 12;11(6):527-534. doi: 10.3920/BM2020.0016. Epub 2020 Oct 9.
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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.
Edgardo Smecuol, MD principal investigator
Dr. C. Bonorino Udaondo Gastroenterology Hospital
Julio C Bai, MD study director
Dr. C. Bonorino Udaondo Gastroenterology Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bifidobacterium infantis NLS super strain (Natren LIFE START®2) in people with Celiac Disease, run by Global Institute of Probiotics at 1 site in Argentina.
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 5 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 24 Aug 2018. 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 Argentina. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Changes in Gastrointestinal Symptom Rating Scale (GSRS) (time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)). 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 NCT03271138, which also lists 1 linked publication.
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 24 Aug 2018.