Clinical Trials Register

Summary
EudraCT Number:	2016-001793-15
Sponsor's Protocol Code Number:	Gastro_CHU_16-1
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-07-12
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2016-001793-15

A.3

Full title of the trial

PROSPECTIVE STUDY OF THE EFFICIENCY OF PROBIOTIC MIXTURE TO IMPROVE LACTOSE DIGESTION AND SYMPTOMS OF LACTOSE INTOLERANCE

ETUDE PROSPECTIVE DE L’EFFICACITE D’UN MELANGE PROBIOTIQUE POUR L’AMELIORATION DE LA DIGESTION DU LACTOSE ET DES SYMPTOMES DE L’INTOLERANCE AU LACTOSE

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

PROSPECTIVE STUDY OF THE EFFICIENCY OF PROBIOTIC MIXTURE TO IMPROVE LACTOSE DIGESTION AND SYMPTOMS OF LACTOSE INTOLERANCE

ETUDE PROSPECTIVE DE L’EFFICACITE D’UN MELANGE PROBIOTIQUE POUR L’AMELIORATION DE LA DIGESTION DU LACTOSE ET DES SYMPTOMES DE L’INTOLERANCE AU LACTOSE

A.4.1

Sponsor's protocol code number

Gastro_CHU_16-1

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	LactoResearch sprl
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	LactoResearch sprl
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	LactoResearch sprl
B.5.2	Functional name of contact point	Fabienne Fonteyn
B.5.3	Address:
B.5.3.1	Street Address	Rue Herman Méganck, 21
B.5.3.2	Town/ city	Isnes
B.5.3.3	Post code	5032
B.5.3.4	Country	Belgium
B.5.4	Telephone number	32(0)81408630
B.5.5	Fax number	32(0)81408639
B.5.6	E-mail	F.Fonteyn@lactoresearch.be

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	M5PR310
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Bifidobacterium longum subsp. infantis
D.3.9.2	Current sponsor code	THT 010201
D.3.9.3	Other descriptive name	BIFIDOBACTERIUM INFANTIS
D.3.9.4	EV Substance Code	SUB32823
D.3.10	Strength
D.3.10.1	Concentration unit	billion CFU billion colony forming units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Bifidobacterium adolescentis
D.3.9.2	Current sponsor code	THT 010701
D.3.9.3	Other descriptive name	BIFIDOBACTERIUM
D.3.9.4	EV Substance Code	SUB32505
D.3.10	Strength
D.3.10.1	Concentration unit	billion CFU billion colony forming units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lactobacillus delbrueckii subsp. bulgaricus
D.3.9.2	Current sponsor code	THT 030301
D.3.9.3	Other descriptive name	LACTOBACILLUS BULGARICUS
D.3.9.4	EV Substance Code	SUB14312MIG
D.3.10	Strength
D.3.10.1	Concentration unit	billion CFU billion colony forming units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lactobacillus reuteri
D.3.9.2	Current sponsor code	THT 030802
D.3.9.3	Other descriptive name	LACTOBACILLUS REUTERI
D.3.9.4	EV Substance Code	SUB32256
D.3.10	Strength
D.3.10.1	Concentration unit	billion CFU billion colony forming units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Streptococcus thermophilus
D.3.9.2	Current sponsor code	THT 070102
D.3.9.3	Other descriptive name	STREPTOCOCCUS THERMOPHILUS
D.3.9.4	EV Substance Code	SUB15399MIG
D.3.10	Strength
D.3.10.1	Concentration unit	billion CFU billion colony forming units
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Mix of 5 lactic acid bacteria (Bifidobacterium infantis , Bifidobacterium adolescentis , Lactobacillus bulgaricus , Lactobacillus reuteri and Streptococcus thermophilus )

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

lactose intolerance

intolérance au lactose

E.1.1.1

Medical condition in easily understood language

dairy product intolerance, lactose malabsorption, milk sugar intolerance

intolérance aux produits laitiers, malabsorption du lactose, intolérance au sucre du lait

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10023682
E.1.2	Term	Lactose intolerant
E.1.2	System Organ Class	100000004861

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Determining the efficacy of a mixture containing bifidobacter infantis tht010201, bifidobacter adolescentis tht010701, lactobacillus bulgaricus tht030301, Lactobacillus reuteri tht030802 and streptococcus thermophilus tht070102 at a concentration of 10 billion CFU to improve lactose digestion of patients intolerant to lactose.

Déterminer l’efficacité d’un mélange contenant du bifidobacter infantis tht010201, bifidobacter adolescentis tht010701, lactobacille bulgaricus tht030301, lactobacille reuteri tht030802 et streptocoque thermophilus tht070102 à la concentration de 10 milliards CFU pour l’amélioration de la digestion du lactose chez des patients intolérants au lactose.

E.2.2

Secondary objectives of the trial

Determining the efficacy of a mixture containing bifidobacter infantis tht010201, bifidobacter adolescentis tht010701, lactobacillus bulgaricus tht030301, Lactobacillus reuteri tht030802 and streptococcus thermophilus tht070102 at a concentration of 10 billion CFU to improve gastrointestinal symptoms of patients intolerant to lactose.

Déterminer l’efficacité d’un mélange contenant du bifidobacter infantis tht010201, bifidobacter adolescentis tht010701, lactobacille bulgaricus tht030301, lactobacille reuteri tht030802 et streptocoque thermophilus tht070102 à la concentration de 10 milliards CFU pour l’amélioration des symptômes gastro-intestinaux chez des patients intolérants au lactose.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age: 45 years, <65 years.
- Patient Agreement with written consent.
- diagnosis of lactose intolerance based on a breath testing (13C-lactose or hydrogen (+ CH4 + CO2) breath test with a dose of 25g of lactose): cumulative recovery of 13CO2 less than 15% for 3 hours, or an increase in the concentration of hydrogen expired more than 20 ppm or 10 ppm when two consecutive measurements during the test of 4 hours compared to the fasting state.
The alveolar air samples are taken every 20 minutes until 60 minutes and then every 30 minutes until 240 minutes for the H2 test (+ CH4 + CO2).
- Patient with a minimum average symptom score of 5/10 (bloating, abdominal pain, flatulence, diarrhea) during breath test.

- Age : 45 ans, < 65 ans.
- Accord du patient avec consentement écrit.
- Diagnostic de l’intolérance au lactose selon les tests au 13C-lactose ou hydrogène (+CH4+CO2) (25g) : taux de récupération cumulé de 13CO2 sur 3 h inférieur à 15%, ou augmentation de la concentration de l’hydrogène expiré de plus de 20 ppm ou de 10 ppm lors de 2 mesures consécutives au cours du test de 4 h par rapport aux valeurs à jeun.
Les échantillons d’air alvéolaire sont pris toutes les 20 minutes jusque 60 minutes, puis toutes les 30 minutes jusque 240 minutes pour le test H2(+CH4+CO2).
- Patient présentant lors du test respiratoire un score symptomatique moyen minimum de 5/10 (ballonnements, douleurs abdominales, flatulences, diarrhée).

E.4

Principal exclusion criteria

- Patients with previous abdominal surgery, with the exception of an appendectomy, cholecystectomy and repair of parietal abdominal hernia.
- history of inflammatory bowel disease.
- Diagnosis of bacterial overgrowth of the small intestine
- Diabetes
- Patients suffering of progressive disease uncontrolled by medical treatment.
- Pregnant or lactating women.
- Use of probiotics in the 2 weeks preceding the study.
- antibiotic use in the month before the study.
- Use of lactase.
- Recent loss of> 10 Kg.
- Fever.
- Noncompliant patients.

- Patients avec antécédents de chirurgie abdominale, à l’exception d’une appendicectomie, cholécystectomie et réfection de hernie pariétale abdominale.
- Antécédent de maladie inflammatoire intestinale.
- Diagnostic de prolifération bactérienne de l’intestin grêle
- Diabète
- Patients porteur d’une pathologie évolutive non contrôlée par un traitement médical.
- Femmes enceintes ou allaitantes.
- Utilisation de probiotiques dans les 2 semaines précédant l’étude.
- Utilisation d’antibiotique dans le mois précédant l’étude.
- Utilisation de lactase.
- Perte récente de > 10 Kg.
- Fièvre.
- Sujets non compliants.

E.5 End points

E.5.1

Primary end point(s)

Given the equipment available at the screening and evaluation visits, one of the two following criteria will be used:
Significant increase (≥ 10%) of cumulative recovery rate of 13C02 following the administration of 13 C-lactose, with the probiotic mixture compared to basal values.
Significant decrease (≥ 40%) of the total amount of hydrogen expired following the administration of lactose, with the probiotic mixture relative to baseline.

Compte tenu de l’équipement disponible lors des visites de screening et d’évaluation, l’un des deux critères ci-dessous sera utilisé :
Augmentation significative (≥ 10%) du taux de récupération cumulé de 13C02 suite à l’administration de 13C-lactose, avec le mélange probiotique par rapport aux valeurs basales.
Diminution significative (≥ 40%) du taux total d’hydrogène expiré suite à l’administration de lactose, avec le mélange probiotique par rapport aux valeurs basales.

E.5.1.1

Timepoint(s) of evaluation of this end point

evaluation visit of supplementation for two weeks

visite d’évaluation d’une supplémentation de 2 semaines

E.5.2

Secondary end point(s)

In parallel to the breath test, a log of gastrointestinal symptoms validated will be used to assess the incidence and severity of symptoms of lactose intolerance.
The severity of symptoms will be assessed using a visual analog scale of 10 cm, ranging from 0 (no symptoms) to 10 (worst possible) to which participants will mark the seriousness of 4 symptoms (bloating, abdominal pain, flatulence, diarrhea).
The logbooks will be completed 4 times: at 3 and 6 hours after challenge with lactose during the visit of screening and at 3 and 6 hours after challenge with lactose after 2 weeks of supplementation.
For each patient, a total score will be calculated on the basis of partial scores for each symptom.
Patient compliance to the protocol is evaluated at the end of supplementation with a questionnaire and counting returned capsules during the evaluation visit of supplementation.

The criteria for secondary judgments used in the analysis of results between the screening visit and assessment visit of supplementation with the probiotic mixture are:
Change of the maximum average of 13CO2 expired for 3 hours.
Proportion of patients with normalization of 13CO2 breath test.
Change of the maximum average of hydrogen expired for 4 hours.
Proportion of patients with normalization of hydrogen breath test.
Change of the total score of severity of symptoms of lactose intolerance (LI SS) between the screening visit and the evaluation visit of supplementation in the group of patients treated with probiotic mixture.
Change of the score of intensity of bloating (sub-score of LI SS) between screening visit and evaluation visit of supplementation.
Change of the score of intensity of abdominal pain (sub-score of LI SS) between screening visit and evaluation visit of supplementation.
Change of the score of intensity of flatulence (sub-score of LI SS) between screening visit and evaluation visit of supplementation.
Modification of diarrhea score (sub-score of LI SS) between visiting screening and evaluation visit of supplementation.
Proportion of patients with moderate or substantial improvement of symptom based on the score or sub-scores of the severity of symptoms of lactose intolerance between screening visit and evaluation visit of supplementation.

En parallèle au test respiratoire, un journal des symptômes gastro-intestinaux validé (9, 10, 11) sera utilisé pour évaluer l'incidence et la sévérité des symptômes de l’intolérance au lactose.
La sévérité des symptômes sera évaluée en utilisant une échelle analogique visuelle de 10 cm, allant de 0 (pas de symptômes) à 10 (le pire possible) sur laquelle les participants marqueront la gravité de 4 symptômes (ballonnements, douleurs abdominales, flatulences, diarrhée).
Les journaux seront complétés 4 fois : à 3 et 6 heures après le challenge au lactose lors de la visite de screening et, à 3 et 6 heures après le challenge au lactose après 2 semaines de supplémentation.
Pour chaque patient, un score total sera calculé sur base des scores partiels pour chaque symptôme.
L’adhésion des patients au protocole est évaluée en fin de supplémentation par un questionnaire et le comptage des gélules retournées lors de la visite d’évaluation de la supplémentation.

Les critères de jugements secondaires utilisés pour l’analyse des résultats entre la visite de screening et la visite d’évaluation de la supplémentation avec le mélange probiotique sont les suivants :
Modification du maximum moyen de 13CO2 expiré sur 3 heures.
Proportion de patients avec normalisation du test respiratoire au 13CO2.
Modification du maximum moyen d’hydrogène expiré sur 4 heures.
Proportion de patients avec normalisation du test respiratoire à l’hydrogène.
Modification du score total de sévérité des symptômes de l’intolérance au lactose (LI SS) entre la visite de screening et la visite d’évaluation de la supplémentation dans le groupe de patients traités par mélange de probiotiques.
Modification du score d’intensité des ballonnements (sous-score de LI SS) entre la visite de screening et la visite d’évaluation de la supplémentation.
Modification du score d’intensité des douleurs abdominales (sous-score de LI SS) entre la visite de screening et la visite d’évaluation de la supplémentation.
Modification du score d’intensité des flatulences (sous-score de LI SS) entre la visite de screening et la visite d’évaluation de la supplémentation.
Modification du score de diarrhée (sous-score de LI SS) entre la visite de screening et la visite d’évaluation de la supplémentation.
Proportion de patients avec amélioration modérée ou importante des symptômes sur la base du score ou des sous-scores de sévérité des symptômes de l’intolérance au lactose entre la visite de screening et la visite d’évaluation de la supplémentation.

E.5.2.1

Timepoint(s) of evaluation of this end point

evaluation visit of supplementation for two weeks

visite d’évaluation d’une supplémentation de 2 semaines

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

désign prétest-posttest sur 1 groupe

one-group pretest-posttest design

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

dernière visite du dernier patient

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Aucun

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-07-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-05

P. End of Trial
P.	End of Trial Status	Ongoing

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