Ignite Creation Date:
2024-05-06 @ 11:00 AM
Last Modification Date:
2024-10-26 @ 12:38 PM
Study NCT ID:
NCT03404440
Status:
COMPLETED
Last Update Posted:
2018-01-19
First Post:
2017-12-30
Brief Title:
Eradication of Helicobacter Pylori With a Lactobacillus Reuteri Strain Plus Proton Pump Inhibitor
Sponsor:
University of Bari
Organization:
University of Bari
Study Overview
Official Title:
Eradication of Helicobacter Pylori With a Lactobacillus Reuteri Strain Combination Strains DSM 17938 and ATCC PTA 6475 and a Proton Pump Inhibitor
Status:
COMPLETED
Status Verified Date:
2018-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Meta-analyses involving 4000 subjects with probiotics added to antimicrobial Helicobacter pylori eradication therapy in populations with antibiotic resistance have reported a mean increase in eradication rate of 122 It is unclear how to translate that result into clinical practice
To evaluate whether administration of Lactobacillus reuteri plus a PPI without antibiotics would eradicate H pylori infections
This was a double-blind placebo-controlled randomized 2 site study of L reuteri 2 x 108 CFU L reuteri DSM 17938 plus 2 x 108 CFU L reuteri ATCC PTA 6475 7 times per day or matching placebo plus 20 mg pantoprazole bid for 4 weeks Cure was defined by negative 13C-UBT 4 weeks after therapy Sample size was based on obtaining 50 cures to be clinically useful as monotherapy
To evaluate whether administration of Lactobacillus reuteri plus a PPI without antibiotics would eradicate H pylori infections
This was a double-blind placebo-controlled randomized 2 site study of L reuteri 2 x 108 CFU L reuteri DSM 17938 plus 2 x 108 CFU L reuteri ATCC PTA 6475 7 times per day or matching placebo plus 20 mg pantoprazole bid for 4 weeks Cure was defined by negative 13C-UBT 4 weeks after therapy Sample size was based on obtaining 50 cures to be clinically useful as monotherapy
Detailed Description:
Aim of study This double-blind study will assess if the combination of PPI and a strain combination Gastrus of Lreuteri can yield higher eradication rates if doses are increased and dose interval shortened The aim is to achieve at least 50 eradication as assessed by UBT
Study Product
Gastrus capsules
2x108 CFU Lactobacillus reuteri DSM 17938 2x108 CFU Lactobacillus reuteri ATCC PTA 6475
Placebo capsules
Identical in shape colour and taste to Gastrus capsules but without the Lactobacillus reuteri components
Both study products are delivered in identical containers containing 30 capsules
Dosing Group 1 1 Gastrus capsule 7 times per day Pantoprazole 20 mg bid Group 2 1 placebo capsule 7 times per day Pantoprazole 20 mg bid One capsule of the Study Product are to be taken every 2-3 hours 7 times per day
The Study Product containers will be collected at the day 28 visit and remaining tablets are counted and compliance checked
40 mg Pantoprazole is to be taken just before breakfast and dinner ie daily dose 80 mg
Length of treatment The optimal length of dosing needed is unknown Saggioro and Francavilla used 30 and 28 days respectively and Dore et al had a 60-day regimen From a practicaleconomicaltolerability point of view a 28-day regimen is suggested in order to shorten the time to triple-therapy for those non-eradicated Those patients with H pylori at the second UBTEndoscopy ie treatment failures will be offered standard eradication therapy
Compliance PP and ITT In order to be assessed as compliant the participant should have consumed at least 75 or other of the allotted doses In order to improve compliance the participants will be equipped with alarm-devices Compliant patients will be assessed as Per-Protocol PP Patients that are non-compliant but have consumed at least one full day of doses ie 14 tablets will be included in the Intention-To-Treat analysis
Outcomes Primary efficacy parameter Number of H pylori-eradicated at 9 weeks as evidenced by Δ-13C-UBT 5 ppm The difference between active and placebo treatment will be compared
Exploratory parameters Changes in GSRS at 4 and 9 weeks as compared to baseline and between groups Changes of the gastric microbiota in the presence of PPI with or without Gastrus
Sample size calculation Assuming that the spontaneous eradication is 5 or less and that the desired eradication rate on active treatment is 50 23 subjects are needed in each group with a power of 90 and a confidence level of 95 To correct for potential drop-outs 25 subjects will be recruited to each group
Ethical committee The study protocol will have to be approved by the local ethical committee before study start Once approved a protocol summary will be posted on clinicaltrialsgov
Study flow and procedures Randomisation labelling Randomisation will be computerised using the tool provided by randomizerorg A third party not otherwise involved in the study will label active and placebo Study Product Randomisation lists will be kept in sealed envelopes at the study sites and a sealed copy will also be kept at BioGaia The envelopes may not be open until all study data have been entered into the database and until the database has been locked However see Serious Adverse Event below
Patients will be entered into the study sequentially by allocating the lowest available remaining randomisation number to the patient
Procedures Histology During endoscopy two biopsy specimens are taken from the antrum one from the angulus and two from the corpus Hp-infection is defined as the presence of typical histology and bacteria on histological examination of biopsies stained by HE and GIEMSA One additional biopsy from the corpus area is placed in PBS with 5 glycerol and stored at - 70 oC until further processing for microbiota analyses see below
Gastric microbiota analysis Bacterial DNA extraction and sequencing for microbiota analyses is performed according to a standardised protocol Willing BP et al 2010 Analysis of community structure focuses on sequencing of targeted regions eg the 16S rRNA gene using the Illumina Miseq high-throughput sequencing platform Sequences are finally processed with the QIIME 180 pipeline Caporaso JG et al 2010
13C-UBT According to standard protocol Gatta L et al 2006 After the first UBT needed for inclusion a second UBT will be performed at 8-9 weeks 4-5 weeks after end of study treatment to assess Hp status
Gastrointestinal Symptom Rating Scale GSRS Participants will be asked to fill out the GSRS questionnaire after inclusion but before taking the first dose of study product at 4 weeks end of treatment and at 8-9 weeks at follow-up UBT Svedlund J et al 1988 Data collection The Principal Investigator will prepare one set of Case Record Forms CRF for each patient in which all data pertinent to the study will be entered
Statistical methods All efficacy parameters will be analysed according to both ITT and PP Safety considerations The investigator is responsible for monitoring the safety of subjects who have entered the study All adverse events AE occurring after any administration of the study product will be followed to the end of the study or until resolution AE will be evaluated by the Investigator and reported in the CRF
Serious adverse events as defined below must be reported to the sponsor within 24 hours of when the investigator became aware of the SAE It is also important to report all adverse events that result in permanent discontinuation of the study product whether serious or non-serious
Adverse Events An adverse event AE is any undesirable medical occurrence in a subject administered a study product regardless of causality assessment An adverse event can therefore be any unfavourable and unintended sign including an abnormal laboratory finding symptom or disease temporally associated with the use of a study product whether or not considered related to the study product All adverse events including observed or volunteered problems complaints or symptoms are to be recorded on the case report form CRF Each adverse event is to be evaluated for duration intensity and causal relationship with the study product or other factors
Subjects should be instructed to report any AE that they experience to the Investigator Investigators should assess for AE at each visit AE occurring during the clinical trial including the follow-up period should be recorded on the appropriate AE CRF To capture the most potentially relevant safety information during a clinical trial it is important that investigators record accurate AE terms on CRF
If discernible at the time of completing an AE in CRF a specific disease or syndrome rather than individual associated signs and symptoms should be identified by the investigator and recorded on the CRF However if an observed or reported sign or symptom is not considered a component of a specific disease or syndrome by the investigator it should be recorded as a separate AE on the CRF Laboratory values will be collected on the laboratory CRF Do not enter changes from baseline in laboratory values on the AE CRF
Serious Adverse Events A serious adverse event SAE is any AE that results in death is immediately life threatening requires or prolongs hospitalisation results in persistent or significant disabilityincapacity is a medically significant event for any reason Breaking the randomisation code In case that the responsible investigator decides that the randomisation code has to be revealed because that the AE may have been caused by the Study Product and that un-blinding is of essence for the further treatment of the patient the following procedure will be followed The responsible investigator will assign a professional otherwise not involved in the study to un-blind the Study Product for the specific patient Heshe will open the sealed envelope find the relevant randomisation number and inform the responsible investigator without revealing any other randomisation numbers Heshe will then re-seal the envelope with transparent tape date and sign on the tape
Study Product
Gastrus capsules
2x108 CFU Lactobacillus reuteri DSM 17938 2x108 CFU Lactobacillus reuteri ATCC PTA 6475
Placebo capsules
Identical in shape colour and taste to Gastrus capsules but without the Lactobacillus reuteri components
Both study products are delivered in identical containers containing 30 capsules
Dosing Group 1 1 Gastrus capsule 7 times per day Pantoprazole 20 mg bid Group 2 1 placebo capsule 7 times per day Pantoprazole 20 mg bid One capsule of the Study Product are to be taken every 2-3 hours 7 times per day
The Study Product containers will be collected at the day 28 visit and remaining tablets are counted and compliance checked
40 mg Pantoprazole is to be taken just before breakfast and dinner ie daily dose 80 mg
Length of treatment The optimal length of dosing needed is unknown Saggioro and Francavilla used 30 and 28 days respectively and Dore et al had a 60-day regimen From a practicaleconomicaltolerability point of view a 28-day regimen is suggested in order to shorten the time to triple-therapy for those non-eradicated Those patients with H pylori at the second UBTEndoscopy ie treatment failures will be offered standard eradication therapy
Compliance PP and ITT In order to be assessed as compliant the participant should have consumed at least 75 or other of the allotted doses In order to improve compliance the participants will be equipped with alarm-devices Compliant patients will be assessed as Per-Protocol PP Patients that are non-compliant but have consumed at least one full day of doses ie 14 tablets will be included in the Intention-To-Treat analysis
Outcomes Primary efficacy parameter Number of H pylori-eradicated at 9 weeks as evidenced by Δ-13C-UBT 5 ppm The difference between active and placebo treatment will be compared
Exploratory parameters Changes in GSRS at 4 and 9 weeks as compared to baseline and between groups Changes of the gastric microbiota in the presence of PPI with or without Gastrus
Sample size calculation Assuming that the spontaneous eradication is 5 or less and that the desired eradication rate on active treatment is 50 23 subjects are needed in each group with a power of 90 and a confidence level of 95 To correct for potential drop-outs 25 subjects will be recruited to each group
Ethical committee The study protocol will have to be approved by the local ethical committee before study start Once approved a protocol summary will be posted on clinicaltrialsgov
Study flow and procedures Randomisation labelling Randomisation will be computerised using the tool provided by randomizerorg A third party not otherwise involved in the study will label active and placebo Study Product Randomisation lists will be kept in sealed envelopes at the study sites and a sealed copy will also be kept at BioGaia The envelopes may not be open until all study data have been entered into the database and until the database has been locked However see Serious Adverse Event below
Patients will be entered into the study sequentially by allocating the lowest available remaining randomisation number to the patient
Procedures Histology During endoscopy two biopsy specimens are taken from the antrum one from the angulus and two from the corpus Hp-infection is defined as the presence of typical histology and bacteria on histological examination of biopsies stained by HE and GIEMSA One additional biopsy from the corpus area is placed in PBS with 5 glycerol and stored at - 70 oC until further processing for microbiota analyses see below
Gastric microbiota analysis Bacterial DNA extraction and sequencing for microbiota analyses is performed according to a standardised protocol Willing BP et al 2010 Analysis of community structure focuses on sequencing of targeted regions eg the 16S rRNA gene using the Illumina Miseq high-throughput sequencing platform Sequences are finally processed with the QIIME 180 pipeline Caporaso JG et al 2010
13C-UBT According to standard protocol Gatta L et al 2006 After the first UBT needed for inclusion a second UBT will be performed at 8-9 weeks 4-5 weeks after end of study treatment to assess Hp status
Gastrointestinal Symptom Rating Scale GSRS Participants will be asked to fill out the GSRS questionnaire after inclusion but before taking the first dose of study product at 4 weeks end of treatment and at 8-9 weeks at follow-up UBT Svedlund J et al 1988 Data collection The Principal Investigator will prepare one set of Case Record Forms CRF for each patient in which all data pertinent to the study will be entered
Statistical methods All efficacy parameters will be analysed according to both ITT and PP Safety considerations The investigator is responsible for monitoring the safety of subjects who have entered the study All adverse events AE occurring after any administration of the study product will be followed to the end of the study or until resolution AE will be evaluated by the Investigator and reported in the CRF
Serious adverse events as defined below must be reported to the sponsor within 24 hours of when the investigator became aware of the SAE It is also important to report all adverse events that result in permanent discontinuation of the study product whether serious or non-serious
Adverse Events An adverse event AE is any undesirable medical occurrence in a subject administered a study product regardless of causality assessment An adverse event can therefore be any unfavourable and unintended sign including an abnormal laboratory finding symptom or disease temporally associated with the use of a study product whether or not considered related to the study product All adverse events including observed or volunteered problems complaints or symptoms are to be recorded on the case report form CRF Each adverse event is to be evaluated for duration intensity and causal relationship with the study product or other factors
Subjects should be instructed to report any AE that they experience to the Investigator Investigators should assess for AE at each visit AE occurring during the clinical trial including the follow-up period should be recorded on the appropriate AE CRF To capture the most potentially relevant safety information during a clinical trial it is important that investigators record accurate AE terms on CRF
If discernible at the time of completing an AE in CRF a specific disease or syndrome rather than individual associated signs and symptoms should be identified by the investigator and recorded on the CRF However if an observed or reported sign or symptom is not considered a component of a specific disease or syndrome by the investigator it should be recorded as a separate AE on the CRF Laboratory values will be collected on the laboratory CRF Do not enter changes from baseline in laboratory values on the AE CRF
Serious Adverse Events A serious adverse event SAE is any AE that results in death is immediately life threatening requires or prolongs hospitalisation results in persistent or significant disabilityincapacity is a medically significant event for any reason Breaking the randomisation code In case that the responsible investigator decides that the randomisation code has to be revealed because that the AE may have been caused by the Study Product and that un-blinding is of essence for the further treatment of the patient the following procedure will be followed The responsible investigator will assign a professional otherwise not involved in the study to un-blind the Study Product for the specific patient Heshe will open the sealed envelope find the relevant randomisation number and inform the responsible investigator without revealing any other randomisation numbers Heshe will then re-seal the envelope with transparent tape date and sign on the tape
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None