Tolerance to an Artisanal Bread in a Population Intolerant of the Conventional Bread and Study of Associated Markers (TOLERBREAD)
The objective of this study is to evaluate the effect of consuming an "artisanal" bread for 15 days on gastrointestinal symptoms in individuals intolerant to "conventional" bread.
"Conventional bread" refers to bread made with refined wheat flour (ash = 0.55% of dry matter), containing gluten, and leavened with baker's yeast (Saccharomyces cerevisiae). "Artisanal bread" refers to bread made with whole wheat flour (ash = 1.50% of dry matter) from an ancient durum wheat variety (Russello) and leavened with sourdough.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Abbreviations:
- GSRS-IBS: Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome
- GIQLI: Gastrointestinal Quality of Life Index
- HADS: Hospital Anxiety and Depression Scale
- FSS: Fatigue Severity Scale
- LBP: Lipopolysaccharide-Binding Protein
Inclusion Visit (visit 0 [V0])
At the inclusion visit (V0) at Avicenne Hospital (Bobigny), participants will receive study instructions and materials. They will have up to 15 days to:
- Complete questionnaires (modified GSRS-IBS, Bristol Stool Scale, GIQLI, HADS, FSS)
- Collect a baseline stool sample, stored at -18°C at home until their first hospital visit (V1).
Wash-out phase (Day-15 [D-15] to Day 0 [D0]):
Participants will follow a gluten-free and low-fructan diet for 15 days. During this period:
- Daily food intake will be recorded in a diary, with meal photos sent to the research team via a dedicated email
- On D-8, participants will complete the modified GSRS-IBS and Bristol Stool Scale.
- On D-1, participants will perform a 24-hour urine collection after ingestion of lactulose (10g) and mannitol (10g) in 200 mL water, divided into three containers:
- First morning urine
- 0-5 h collection after sugar ingestion (fasting except water)
- 5-24 h collection Stool will also be collected on D-1 and stored at 4°C until V1.
First investigation day (Day 0 [D0] - V1):
At 9 a.m., participants arrive the Clinical Research Center (at Avicenne Hospital) with their stool and urine samples.
After completing the questionnaires (modified GSRS-IBS, GIQLI, HADS, FSS, and Bristol Stool Scale), a venous catheter will be inserted for blood sampling.
A 10 mL blood sample will be collected before the test meal. Participants will then consume the test meal (105 g of "artisanal" bread with water).
Postprandial blood samples (2 mL each) will be collected every 30 minutes for 3 hours (total blood volume: 22 mL) The modified GSRS-IBS questionnaire will be completed every hour during the postprandial period If a bowel movement occurs during the visit, the stool sample collected at that time may be used to replace the one collected the previous day.
Intervention phase (D1 to D14):
Participants will continue the same gluten-free, low-fructan diet, with the addition of the "artisanal" bread, which will serve as the sole source of gluten source and the main source of fructans.
- D1: 75 g of bread
- D2: 100 g of bread
- D3-14: 125 g of bread daily (≈ 8.5 g gluten, <1.2 g fructans) Bread consumption may be distributed throughout the day. On D8, participants will again complete the modified GSRS-IBS and Bristol Stool Scale.
Second investigation day (D15 - V2):
On D14, participants will repeat the 24-hour urine and stool collection as previously described. On D15, they will return to the research center and undergo the same procedures as V1.
Measurements:
- Questionnaires: modified GSRS-IBS (gastrointestinal symptoms), GIQLI, HADS, FSS.
- Blood: LBP (marker of inflammation), zonulin (marker of intestinal permeability), glucose, insulin.
- Urine: lactulose and mannitol, with calculation of the lactulose/mannitol ratio as a marker of intestinal permeability.
- Stool: microbial community analysis (microbiota) and fecal calprotectin (marker of inflammation). Baseline stool samples (before wash-out phase) will also be used to inoculate an artificial colon model for later investigation of the effects of bread on the microbiota.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Fabien Wuestenberghs
- Número de teléfono: +330148952276
- Correo electrónico: fabien.wuestenberghs@aphp.fr
Copia de seguridad de contactos de estudio
- Nombre: Claire Gaudichon
- Número de teléfono: +33144081829
- Correo electrónico: claire.gaudichon@agroapristech.fr
Ubicaciones de estudio
-
-
-
Bobigny, Francia, 93000
- Reclutamiento
- Centre de Recherche sur Volontaires
-
Contacto:
- Mourad Benallaoua
- Correo electrónico: mourad.benallaoua@aphp.fr
-
Contacto:
- Suzette Maurinier
- Correo electrónico: suzette.maurinier@aphp.fr
-
-
Île-de-France Region
-
Bobigny, Île-de-France Region, Francia, 93000
- Aún no reclutando
- Centre de Recherche sur Volontaires (CRV)
-
Contacto:
- Suzette Maurinier
- Número de teléfono: +331 48 95 74 33
- Correo electrónico: suzette.maurinier@aphp.fr
-
Investigador principal:
- Fabien Wuestenberghs
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Normal weight (18 < BMI < 25 kg.m-2)
- Male or female
- 18 to 65 years old
- Adults reporting intolerance to "conventional" bread
- Absence of celiac disease
- Affiliated to a social security scheme
- Free, informed and express consent
Exclusion Criteria:
- People under protective supervision: legal guardianship, tutorship or curatorship
- People with eating disorders (anorexia, bulimia, binge eating)
- Any known food allergy
- Women who are pregnant or potentially pregnant (based on a positive urine pregnancy test at inclusion)
- Breastfeeding women
- Alcohol abuse (>2 drinks/day). At the time of inclusion, the investigator will assess whether the participant exhibits harmful alcohol consumption
- Untreated hypertension, uncontrolled diabetes, or diseases of the digestive tract (excluding functional intestinal disorders), liver, kidneys, or severe heart disease. The investigator will assess the presence of these conditions on standard clinical criteria and the participants' self-reported medical history at the time of inclusion
- Participation in a clinical study in the three months preceding the study
- Absence of express consent
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Artisanal Bread
"Artisanal" bread is made with wholemeal flour (ash = 1.50% of dry matter) from an ancient durum wheat (Russello variety) and leavened with sourdough. "Artisanal" bread contains 6.8g of gluten and less than 1g of frutans per 100g. |
During the second part of the study (from Day 1 [D1] to Day 14 [D14]), participants will consume the "artisanal" bread on a daily basis. Dose: D1 = 75g; D2 = 100g; from D3 to D14: 125g/day On D0 and D15, volunteers will come to the hospital for 3 hours of postprandial testing. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Intensity of gastrointestinal symptoms
Periodo de tiempo: Scores at Day 0 [D0] and Day 15 [D15]
|
The severity of gastrointestinal symptoms will be assessed using a score from the modified GSRS-IBS questionnaire used in this study. This score consists of 13 questions ranging from 1 (Not at all) to 7 (Very severely) on a Likert scale. Thus, the total score can range from 13 to 91, with higher scores indicating more severe gastrointestinal symptoms and, consequently, lower tolerance. The scores obtained before and after the diet including the "artisanal" bread will be compared. |
Scores at Day 0 [D0] and Day 15 [D15]
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Intensity of gastrointestinal and extraintestinal symptoms
Periodo de tiempo: Scores at Day 0 [D0] and Day 15 [D15]
|
The intensity of gastrointestinal and extra-intestinal symptoms will be assessed using the total score of the modified version of the GSRS-IBS questionnaire. Scores obtained before and after the diet including the "artisanal" bread will be compared. The score is measured on a 7-point Likert scale, ranging from 1 (Not at all) to 7 (Very severely). The questionnaire consists of 28 questions, so total scores can range from 28 to 196, with higher scores indicating more severe gastrointestinal and extra-intestinal symptoms and, therefore, lower tolerance. |
Scores at Day 0 [D0] and Day 15 [D15]
|
|
Validity of the modified GSRS-IBS
Periodo de tiempo: Scores of the two questionnaires at Day [D0] and Day [D15]
|
Correlations between the scores from the GSRS-IBS and the modified GSRS-IBS used in this study will be analyzed. The GSRS-IBS score can be obtained from the modified GSRS-IBS questionnaire. This questionnaire consists of 7-point Likert scale ranging from 1 (No discomfort at all) to 7 (Very severe discomfort) for 13 items. The total score therefore ranges from 13 to 91. An increase in this score indicates greater gastrointestinal discomfort and, consequently, lower tolerance. The modified GSRS-IBS questionnaire comprises 28 items scored on a 7-point Likert scale, ranging from 1 (Not at all) to 7 (Very severely). Thus, the total score of this questionnaire ranges from 28 to 196. An increase in this score indicates greater gastrointestinal symptoms and, consequently, lower tolerance. These two scores will be compared, and their correlation analyzed. |
Scores of the two questionnaires at Day [D0] and Day [D15]
|
|
Comparison between volunteers' perceived tolerance of "artisanal" bread and measured tolerance
Periodo de tiempo: Scores at Day 0 [D0] and Day 15 [D15]
|
In addition to the intensity scores calculated for each symptom (the sum of which constitutes an objective total score), participants will give a global subjective assessment of their tolerance to the "artisanal" bread using a scale from 0 (absence of symptoms) to 10 (extremely intense symptoms).
The objective and subjective scores will then be compared, and their correlation analyzed.
|
Scores at Day 0 [D0] and Day 15 [D15]
|
|
Clinical profile of response to the "artisanal" bread
Periodo de tiempo: These scores are measured at Day 0 [D0], Day 8 [D8] and Day 15 [D15].
|
Individual symptoms will be grouped into symptom groups (pain, reflux, indigestion, diarrhea and constipation).
A score will be calculated for each groupe, and these scores will be compared.
|
These scores are measured at Day 0 [D0], Day 8 [D8] and Day 15 [D15].
|
|
Evaluation of intestinal permeability
Periodo de tiempo: Measured on Day D0 [D0] and Day 15 [D15]
|
Intestinal permeability will be assessed by measuring serum zonulin levels and the urinary lactulose/mannitol ratio.
|
Measured on Day D0 [D0] and Day 15 [D15]
|
|
Evaluation of intestinal inflammation
Periodo de tiempo: Serum LBP : measured on Day 0 [D0] and Day D15 [D15] Fecal calprotectin : measured in stool samples collected at Day-1 [D-1] and Day 14 [D14].
|
Intestinal inflammation will be assessed by measuring serum LBP and faecal calprotectin.
|
Serum LBP : measured on Day 0 [D0] and Day D15 [D15] Fecal calprotectin : measured in stool samples collected at Day-1 [D-1] and Day 14 [D14].
|
|
Microbiota composition
Periodo de tiempo: Determined in stool samples collected at visit 0 [V0], on Day -1 [D-1] and Day 14 [D14]
|
The relative abundance of bacterial genera in stool samples at the end of each diet (with and without bread) will be compared. Stool samples will also be collected at inclusion (visit 0 [V0]) to determine the baseline microbiota and to inoculate an in vitro artificial colon model. |
Determined in stool samples collected at visit 0 [V0], on Day -1 [D-1] and Day 14 [D14]
|
|
Tolerance profiles for "artisanal" bread
Periodo de tiempo: From the enrollment (visit 0 [V0]) to the end of the study (Day 15 [D15])
|
Exploration of tolerance profiles to "artisanal" bread without a priori, and their characterization based on clinical data (questionnaires) and biological markers (inflammation, intestinal permeability, and microbiota).
|
From the enrollment (visit 0 [V0]) to the end of the study (Day 15 [D15])
|
|
Postprandial glucose responses measured after consumption of the test meal ("artisanal bread")
Periodo de tiempo: Measured at 0; 0.5; 1; 1.5; 2; 2.5 and 3 hours after test meal
|
Blood glucose levels measured every 30 minutes for 3 hours after the test meal
|
Measured at 0; 0.5; 1; 1.5; 2; 2.5 and 3 hours after test meal
|
|
Postprandial insulin responses measured after consumption of the test meal ("artisanal bread")
Periodo de tiempo: Measured at 0; 0.5; 1; 1.5; 2; 2.5 and 3 hours after test meal
|
Blood insulin levels measured every 30 minutes for 3 hours after the test meal
|
Measured at 0; 0.5; 1; 1.5; 2; 2.5 and 3 hours after test meal
|
|
Substrate oxidation rates
Periodo de tiempo: Measured at 0; 0.5; 1.5 and 2.5 hours after test meal
|
Fat and glucose oxidation assessed by measuring respiratory exchanges using indirect calorimetry
|
Measured at 0; 0.5; 1.5 and 2.5 hours after test meal
|
|
H2 concentrations in exhaled air
Periodo de tiempo: Measured at 0; 0.5; 1; 1.5; 2; 2.5 and 3 hours after test meal
|
H2 concentration in air measured every 30 minutes for 3 hours after test meal
|
Measured at 0; 0.5; 1; 1.5; 2; 2.5 and 3 hours after test meal
|
Colaboradores e Investigadores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- TOLERBREAD
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .