Probiotics and Biomarkers in Irritable Bowel Syndrome (BIO-IBS)
The Impact of Probiotics on Biomarkers and Symptom Severity in Irritable Bowel Syndrome
The goal of this double-blind parallel-arm randomized controlled trial is to learn if a probiotic supplement (containing a new strain derived from L. reuteri) alters outcomes related to symptom severity and transit time in adults with irritable bowel syndrome (IBS). The main question it aims to answer is:
Does the probiotic alter IBS symptom severity?
Researchers will compare the probiotic to a placebo (a lookalike substance that contains no probiotic) to see if the probiotic works to alter outcomes.
Participants will:
Be randomized to either take the probiotic supplement or placebo supplement daily for 12 weeks.
Visit the lab for 4 study visits (visit 1: screening and informed consent; visit 2: randomization, data collection, beginning the intervention; visit 3: end of intervention and data collection; visit 4: 3 month post intervention follow up and data collection).
Provide biological samples (blood, stool, saliva, urine) Complete questionnaires
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
The BIO-IBS study is a double-blind, randomized, placebo-controlled clinical trial investigating whether a combination probiotic improves symptoms in adults with irritable bowel syndrome (IBS). The trial also explores biological mechanisms and predictors of treatment response.
Background & Rationale IBS is a common disorder of gut-brain interaction (~4% prevalence in Sweden). Current treatments include dietary, pharmacological, and psychological approaches. Increasing evidence suggests the gut microbiome plays a key role, prompting interest in probiotics.
Aims
1. Evaluate effect of probiotic combination on IBS symptoms. 2, Identify predictors of response. 3. Investigate IBS pathophysiology and biomarkers.
Study Design
Type: Double-blind, randomized, placebo-controlled, parallel-group Participants: 252 adults with IBS Randomization: 1:1 (probiotic vs placebo) Treatment duration: 12 weeks Follow-up: 3 months post-treatment Timeline: Recruitment starting April 2026 lasting ~3 years
Participants Inclusion Criteria
Adult (≥18 years), IBS (Rome IV criteria) IBS-SSS > 75 BMI 18.5-35 Able to consent and complete Swedish questionnaires
Key Exclusion Criteria
Significant gastrointestinal or systemic disease Recent antibiotics (within 3 months) or probiotics (within 2 weeks) Opioid use Pregnancy/breastfeeding Significant lab abnormalities (e.g., high fecal calprotectin) Major lifestyle/treatment changes
Intervention
Active treatment: Tablet containing both L. reuteri strains Placebo: Identical without bacteria Dose: 1 tablet twice daily Duration: 12 weeks Compliance ≥80% required for per-protocol analysis.
Outcomes Primary Outcome
Change in IBS symptom severity (IBS-SSS) from baseline to 12 weeks (intervention vs placebo)
Secondary Outcomes
Proportion achieving ≥50 or ≥100 point IBS-SSS reduction Gastrointestinal symptoms (GSRS-IBS) Pain reduction Quality of life (IBSQOL) Work productivity (WPAI:IBS) Transit time (gut motility) Adverse events Sustainability of effects (3-month follow-up)
Exploratory Outcomes
Stool consistency/frequency Biomarkers (microbiome, immune, metabolomics, etc.) Psychological and lifestyle factors Dietary influences Mechanistic insights into IBS
Study Procedures Visits Screening (2-8 weeks before randomization Consent, questionnaires, biological samples, diaries
Randomization (Day 0) Baseline assessments and start of treatment
During intervention Regular symptom tracking Phone follow-up at week 6
End of treatment (12 weeks) Repeat assessments and samples
Follow-up (3 months later) Long-term outcomes
Optional (Facultative) Assessments Rectal sensitivity (barostat) Sigmoidoscopy ± confocal endomicroscopy MRI (motility and colonic volume)
Measurements
Questionnaires: IBS-SSS, GSRS-IBS, HADS, PHQ-15, IBSQOL, stress, work productivity Biological samples: blood, stool, urine, saliva Gut function: transit time (radiopaque markers and sweetcorn method) Diet: food frequency and recall diaries
Statistical Considerations Sample size: 252 participants (powered to detect clinically meaningful IBS-SSS difference)
Populations:
Intention-to-treat (all randomized) Per-protocol (≥80% compliance, no major deviations) Analysis plan: Defined in a Statistical Analysis Plan No interim analysis
Safety Probiotics considered safe with minimal risk (mainly transient flatulence). Adverse events will be recorded and classified by severity and causality. IBS symptom fluctuations are not counted as adverse events unless worsened.
Ethics & Data Handling Conducted according to Declaration of Helsinki and ICH-GCP. Participants give informed consent and can withdraw anytime. Data are pseudonymized and securely stored (REDCap)
Risk-Benefit Assessment Low risk due to established safety of L. reuteri strains Moderate participant burden (questionnaires, sample collection) Optional procedures may cause discomfort but are controlled and voluntary Potential benefit: improved IBS symptoms and better understanding of disease mechanisms
Key Strengths Large sample size Rigorous randomized controlled design Comprehensive symptom, biological, and mechanistic assessment Long follow-up
Conclusion This study aims to determine whether a novel probiotic combination improves IBS symptoms and to identify biological and clinical predictors of response, contributing to more personalized treatment strategies in IBS.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: MagTarmlab office
- Número de telefone: 0046313428107
- E-mail: magtarmlab.su@vgregion.se
Estude backup de contato
- Nome: Magnus Simren, MD, PhD
- Número de telefone: 0046313428107
- E-mail: magnus.simren@medicine.gu.se
Locais de estudo
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Gothenburg, Suécia, 413 45
- Recrutamento
- Mag-tarmlab, Sahlgrenska University Hospital
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Contato:
- MagTarmlab
- Número de telefone: +46 31 342 81 07
- E-mail: magtarmlab.se@vgregion.se
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Diagnosed with IBS according to ROME V criteria
- IBS-SSS greater than or equal to 75
- Adult over 18 years old
- BMI 18.5-35 kg/m2
- Able to understand the participant information sheet and willing to comply with the study protocol
- Able to give informed consent
- Able to complete the Swedish questionnaires
Exclusion Criteria:
- History of any gastroenterology disease including coeliac disease, heart, liver, neurological, or current psychiatric disease, diabetes, any surgery to the abdomen that affects intestinal function (not including cholecystectomy, appendectomy, ceasarean section).
- The use of opioids 1 month prior to screening and throughout the study
- The use of probiotic supplements from 14days before randomization and during the study (not including foods with probiotic components)
- Consumption of antibiotics 3 months prior to screening and throughout the study
- The start of any new drugs that affect the gastrointestinal tract or symptoms within the last month before the start of the study. As well as the start of new diets of psychological therapy as treatment for IBS symptoms.
- Participation in any medical research during the last month
- Clinically relevant lab abnormalities at the time of screening (fecal calprotectin greater than or equal to 150 ug/g as absolute cutoff. If calprotectin is between 50 - 150ug/g the decision is made on clinical judgement)
- Pregnancy, plan to become pregnant during the study, breastfeeding
- alcohol consumption >14 units per week
- Use of recreational active drugs during 1 month before screening or during the study
- Use of medication that primarily affects bowel function, transit time, stool consistency 2 weeks before the intervention or during the 12 week intervention period
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Intervention
Adults with IBS who have been randomized to receive the intervention
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Probiotic using a new strain derived from L. reuteri.
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Comparador de Placebo: Control
Adults with IBS who have been randomized to receive the placebo
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A placebo supplement that is identical to the probiotic in formulation and packaging except that the probiotic bacteria is not present.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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IBS symptom severity (IBS-Symptom-Severity-Score)
Prazo: Screening (15-60 days pre-intervention), baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Screening (15-60 days pre-intervention), baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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General global assessment: satisfactory adequate relief of symptoms from baseline to end of intervention between arms
Prazo: During intervention (days 14, 28, 42, 56, 70), end of intervention (day 84)
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The proportion of individuals with greater or equal to 50% of assessments with an adequate relief of symptoms
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During intervention (days 14, 28, 42, 56, 70), end of intervention (day 84)
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General global assessment: worst pain over the last 24 hours, intervention group vs placebo group reduced between baseline and end of intervention between arms
Prazo: During intervention (days 14, 28, 42, 56, 70), end of intervention (day 84)
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The proportion of individuals with greater or equal to 50% of assessments between baseline and end of intervention, and a greater than or equal to 30% decrease in worst pain during the last 24 hours compared to baseline
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During intervention (days 14, 28, 42, 56, 70), end of intervention (day 84)
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Gastrointestinal Symptom Rating Scale- IBS (GSRS-IBS)
Prazo: Screening (15-60 days pre-intervention), baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Change in Gastrointestinal Symptom Rating Scale- IBS (GSRS-IBS) scores over time between arms The GSRS uses a 7- point Likert scale. Total scores can range from 15 - 105 with higher scores indicating worse symptom rating |
Screening (15-60 days pre-intervention), baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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IBS-quality of life (IBS-QoL)
Prazo: Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Change in IBS-quality of life (IBS-QoL) scores over time between arms The IBS-QoL is a 34-item scale that uses a 5-point Likert scale with total scores ranging from 0-100, where higher scores indicate better quality of life |
Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Work Productivity and Activity Impairment:IBS (WPAI:IBS)
Prazo: Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Change in Work Productivity and Activity Impairment:IBS (WPAI:IBS) scores over time between arms The WPAI:IBS consists of 6 items regarding employment status, hours of work missed because of IBS, hours missed because of other reasons, hours actually worked, how much IBS affected productivity of working (VAS of 0 to 10), how much IBS affected regular activities (VAS of 0 to 10). Total scores are expressed as percentage of impairment/productivity lost with higher scores indicating greater impairment |
Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Change in oro-anal transit time from baseline to end of intervention between groups: Radiopaque markers
Prazo: Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84)
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Participants will take oral tablets that are radiopaque markers following a specific protocol beginning from 7 days prior to attending the study visit.
Each day they will swallow one set of radiopaque markers with water, then on day 7 a nurse will conduct an X-ray of the abdomen to show the location of the markers in the bowel.
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Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84)
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Change in oro-anal transit time from baseline to end of intervention between groups: sweetcorn
Prazo: Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84)
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Sweetcorn oro-anal transit time will be measured using a specific protocol.
7 days before attending the study visit the participants will be advised to eat 100g of sweetcorn at 0800 with minimal chewing.
Following this, each time they open their bowel for the next 6 days they will be advised to visually inspect the stool for sweetcorn and record whether or not they see the sweetcorn in a diary.
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Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84)
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Hospital Anxiety and Depression Scale (HADS)
Prazo: Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Change in Hospital Anxiety and Depression Scale (HADS) scores over time between groups. The HADS is a 14-item questionnaire (with 2 subscales: HADS-Depression (7 items) and HADS-Anxiety (7 items), with each item rated on a 4 point Likert scale. Total scores range from 0 - 21. Higher scores indicate worse symptoms for anxiety and depression |
Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Patient Health Questionnaire (PHQ)
Prazo: Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Change in Patient Health Questionnaire (PHQ) scores over time between groups The PHQ is a 15-item questionnaire with each item rated on a 3-point Likert scale. Total scores range from 0-30 with higher scores indicating greater somatic symptom burden |
Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Validation of the measurement of oro-anal transit time using sweetcorn vs radiopaque markers
Prazo: Baseline to end of intervention (12 weeks)
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Baseline to end of intervention (12 weeks)
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Fecal samples
Prazo: Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Fecal samples will be analysed in relation to factors regarding predictors of IBS symptoms and response to intervention (including gut microbiome and fecal metabolites)
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Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Urine samples
Prazo: Baseline (day 0 of intervention)
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Urine samples will be analysed in relation to factors regarding predictors of IBS symptoms (including urinary metabolites)
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Baseline (day 0 of intervention)
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Saliva samples
Prazo: Baseline (day 0 of intervention)
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Saliva samples will be analysed in relation to factors regarding predictors of IBS symptoms (including salivary protease)
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Baseline (day 0 of intervention)
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Dietary intake - 3 day diet diaries
Prazo: Screening (15-60 days pre-intervention), baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Dietary intake will be recorded prior to and throughout the study period in seven 3-day diet diaries and analysed in relation to predictors of IBS symptoms and response to intervention
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Screening (15-60 days pre-intervention), baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Unprepared sigmoidoscopy (+ biopsy and blood serum to measure permeability) with confocal laser endomicroscopy (CLE)
Prazo: After screening, but pre-randomization (60 - 15 days pre-randomization)
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This is an opt-in outcome for participants to ascertain gut permeability in relation to IBS symptom predictors
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After screening, but pre-randomization (60 - 15 days pre-randomization)
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MRI colon to measure colonic gas volumes
Prazo: After screening, but pre-randomization (60 - 15 days pre-randomization)
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This is an opt-in outcome for participants to ascertain colonic gas volumes in relation to IBS symptom predictors
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After screening, but pre-randomization (60 - 15 days pre-randomization)
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Small bowel motility MRI
Prazo: After screening, but pre-randomization (60 - 15 days pre-randomization)
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This is an opt-in outcome for participants to ascertain small bowel motility in relation to IBS symptom predictors
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After screening, but pre-randomization (60 - 15 days pre-randomization)
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ROME V
Prazo: Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Changes in stool consistency and frequency measured using the ROME V questionnaire The ROME V is a diagnostic questionnaire for disorders of the gut-brain interaction. Changes in stool consistency and frequency are related to a subset of questions in the Rome V (Q54 - 60). Items are rated on a 10-point Likert scale rated as a percentage of 0 - 100% regarding frequency of symptoms in the last 3 months, including: abdominal pain/ discomfort, how often abdominal pain happened close in time to a bowel movement, how often stools were harder than usual, how often stools were softer than usual, how often stools were more frequent than usual, and how often stools were less frequent than usual. |
Baseline (day 0 of intervention), during intervention (days 14, 28, 42, 56, 70), end of intervention (day 84), 3 month follow up post intervention
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Rectal sensitivity barostat
Prazo: After screening, but pre-randomization (60 - 15 days pre-randomization)
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This is an opt-in outcome for participants to ascertain rectal sensitivity in relation to IBS symptom predictors. A balloon is inserted and inflated in the rectum in a controlled setting. The patient indicates when defined sensory thresholds are reached (first feeling of the balloon, urge to empty bowel, discomfort or pain). When the patient indicates discomfort or pain, or another reason to stop, the balloon inflation will be stopped. |
After screening, but pre-randomization (60 - 15 days pre-randomization)
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Rectal sensitivity with Physical Reactions to Emotions Scale (PRES)
Prazo: After screening, but pre-randomization (60 - 15 days pre-randomization)
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This is an opt-in outcome for participants to ascertain rectal sensitivity in relation to IBS symptom predictors Alongside the rectal barostat, participants will complete the PRES, a 9-item questionnaire measured on a 4-item Likert scale. Total scores can range from 0 = 27 with higher scores indicating more frequent physical reactions to the rectal barostat |
After screening, but pre-randomization (60 - 15 days pre-randomization)
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Magnus Simren, MD PHD, Göteborg University
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- BIO-IBS 2025-04788-01-805801
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