Ignite Creation Date:
2024-05-06 @ 3:00 PM
Last Modification Date:
2024-10-26 @ 1:41 PM
Study NCT ID:
NCT04491734
Status:
COMPLETED
Last Update Posted:
2021-08-30
First Post:
2020-06-23
Brief Title:
Tolerability Study of a Novel Microbiome Therapeutic in Subjects With Gastroesophageal Reflux Disease
Sponsor:
ISOThrive Inc
Organization:
ISOThrive Inc
Study Overview
Official Title:
Open Label Tolerability Study of a Novel Microbiome Therapeutic ISOT-101 Maltosyl-Isomalto-oligosaccharides MIMO in Subjects With Gastroesophageal Reflux Disease
Status:
COMPLETED
Status Verified Date:
2021-08
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:
This is a remote study No office visits required The purpose and efficacy endpoint of this study is to assess whether GERD patients tolerate ISOT-101 In addition usage of the ReQuest validated questionnaire to measure GERD symptoms will be explored as well as usage of the validated SF-36 quality of life QoL questionnaire Each subject serves as hisher own control Relative tolerability in subjects both on and off proton pump inhibitors PPIs will be compared Subjects naive to PPIs currently taking PPIs and historically on PPIs will be evaluated with ReQuest and QoL scores In addition survey measurements will be taken on a subset of 10 subjects that are non-responders to PPIs These will not be included in the statistical analysis with the above groups A tertiary endpoint of this study is to assess any relevant adverse events that occur
Detailed Description:
Introduction and Background GERD is found in about one-third of the population of the USA About 20 to 45 million people have been diagnosed by a doctor and have been prescribed daily acid reducing medications called proton pump inhibitors PPIs which are the mainstay of medical therapy for GERD PPIs dont cure GERD and many patients take them indefinitely for adequate symptom control In addition clinicians and researchers have identified concerns with regard to chronic PPI use and the resulting possible adverse effects due to chronic diminished gastric acid production The potential adverse effects with reasonable association to PPIs include osteoporosis fractures pneumonia C difficile colitis small intestinal bacterial overgrowth SIBO hypomagnesemia vitamin B-12 deficiency and iron deficiency anemia The frequent claims of potential PPI adverse effects that appear in public media has also worried patients In a recent article 46 of patients on PPIs want to discontinue them and 39 unfortunately have tried to do so without medical advice increasing the risk of GI bleeding Barretts esophagus and esophageal adenocarcinoma Other patients such as those at risk for C difficile infection osteoporosis the elderly patients with small intestinal bacterial overgrowth among others should not be on PPIs indefinitely Unfortunately there has been no reliable cure or adequate alternative that does not share adverse effects ISOThrive has produced a proprietary digestion-resistant carbohydrate ISOT-101 a specific formulation of maltosyl-isomalto-oligosaccharides MIMO that serves as a prebiotic feeding selected bacteria that commonly inhabit the human GI tract MIMO has an FDA Generally Recognized As Safe GRAS status Since the dawn of agrarian societies grains were converted to bread using a sourdough fermentation process MIMO molecules are generally found in such breads These forms of breads and other sources of MIMO have been inadvertently removed from the daily diet and so can no longer feed selective bacteria that may have played a protective role for prior generations
Study Rationale This is a remote study No office visits required The purpose and efficacy endpoint of this study is to assess whether GERD patients tolerate ISOT-101 In addition usage of the ReQuest validated questionnaire to measure GERD symptoms will be explored as well as usage of the validated SF-36 quality of life QoL questionnaire Each subject serves as hisher own control Relative tolerability in subjects both on and off proton pump inhibitors PPIs will be compared Subjects naïve to PPIs currently taking PPIs and historically on PPIs will be evaluated with ReQuest and QoL scores In addition survey measurements will be taken on a subset of 10 subjects that are non-responders to PPIs These will not be included in the statistical analysis with the above groups A tertiary endpoint of this study is to assess any relevant adverse events that occur
Study Design The test material is ISOT-101 It is an approximately 90 pure maltosyl-isomalto-oligosacchride MIMO prebiotic syrup produced by bacterial fermentationbio-conversion of sucrose and maltose It is taken 1g daily at bedtime
Subjects will have been previously diagnosed with GERD and will fall into one of the following four groups
1 Symptomatic subjects currently not taking PPI therapy and who are naive to PPIs
2 Symptomatic subjects currently not taking PPI therapy who were responsive to prior PPI therapy either QD or BID and who have been off PPIs for at least four weeks
3 Symptomatic subjects currently taking PPI therapy either QD or BID who are partial responders to PPIs
4 10 symptomatic subjects who have had no benefit from PPIs and have not taken PPIs for at least 4 weeks
All subjects will have active GERD symptoms as determined by the ReQuest validated GERD specific questionnaire The study has been designed to have each subject serve as their own control so there will be no placebo arm Each subject will receive ISOT-101 according to the protocol Recruitment for subjects with GERD will be by referrals from GI specialists primary care physicians and general advertising Each candidate will be given information as to how to contact the study coordinator to enroll in the study The goal is to assess 110 subjects after the Screening Phase including the 10 subjects who did not respond to PPIs All subjects will be screened per the eligibility criteria delineated in this protocol by the study coordinator
Two phases have been designed into this study Phase 1 is the Screening Phase SP Phase 2 is the Tolerability Phase TP Subjects will be instructed to take a daily GERD symptom questionnaire the ReQuest Short Version daily throughout the study At five timepoints specific scores will be established for comparison and statistical analysis These timepoints are 1 SP7 - baseline on current therapy if any without ISOT-101 2 TP7 - 1 week on both current therapy if any and ISOT-101 3 TP14 - 2 weeks on both current therapy if any and ISOT-101 4 TP21 - 3 weeks on both current therapy if any and ISOT-101 5 TP28 - 4 weeks on both current therapy if any and ISOT-101 At each of these timepoints subjects will also complete the ReQuest Long Version and the SF-36 Health Survey QoL validated questionnaires They need not complete the ReQuest Short Version on days that the ReQuest Long Version is required Subjects will report any usage of all GERD medications PPI H-2 antagonists antacid throughout their study participation
Enrollment An adequate number of individuals will need to be screened during the Screening Phase using disease specific validated questionnaires to yield approximately 110 qualified subjects to enter and likely complete the Tolerability Phase of the study Recruitment may involve primary care physicians andor gastroenterologists who will make IRB approved study information available to patients who are symptomatic for GERD Such patients will include those partial responders on PPI therapy those who responded to PPIs but have previously stopped their PPI therapy for at least 4 weeks those who are naive to PPI therapy and 10 subjects that have had no benefit from PPIs and have not been on PPI therapy for at least 4 weeks Deviations from the inclusion and exclusion criteria will not be allowed so as not to jeopardize the scientific integrity of the study regulatory acceptability or subject safety Therefore adherence to the criteria as specified in the protocol is essential
All subjects will be required to sign an IRB-approved informed consent or e-consent that complies with the requirements of both 21 CRF Part 50 and Health Insurance Portability and Accountability Act HIPAA before entering the study
The duration of the study is defined for each subject as the date a signed written informed consent or e-consent is provided through Tolerability Phase Day 28 Total participation in study may last up to 8 weeks A comparable gender distribution is sought for the final analysis therefore the ratio of male to female or female to male subjects completing the Tolerability Phase will be capped at 60 of the total
Concomitant Medications and Washout Periods GERD medications Subjects currently taking PPI therapy either QD or BID who are partial responders to PPIs may continue taking PPIs throughout the study as needed Subjects not taking PPIs prior to being enrolled may also take PPIs as needed Antacids or H-2 antagonists may be taken regularly or intermittently as needed throughout the conduct of this study All GERD-related medications taken by the subject should be recorded daily via the daily electronic survey
Prebiotic andor probiotic supplements Enrolled subjects must stop taking all prebiotic andor probiotic supplements 2 weeks prior to entering the Screening Phase of the study Subjects must refrain from taking prebiotic or probiotic supplements through Tolerability Phase Day 28
Sleep medications Enrolled subjects taking medications for sleep disorders must be on a stable dose at time of consent and continue at said dose through Tolerability Phase Day 28
Antibiotics Subjects must not have taken antibiotics within 6 months prior to signing of consent or at any time during their participation in the study If antibiotics are prescribed to the subject during study participation subject must be withdrawn from study and discontinue daily ISOT-101 immediately
All study product sachets used and unused must be returned to Investigator for product accountability
Subject Study Flow Process
No study-related activities will be performed and no subject data will be collected prior to completion of the informed consent process
Screening Phase SP
To enter the SP subjects must have previously been diagnosed with GERD be symptomatic on their current therapy or lack of therapy and fall into one of the 4 study groups noted in Section 40 above The SP will last for 7 days Subjects who do not qualify at any point during the SP will not be allowed to move into the Tolerability Phase TP The TP will last 28 days beginning with first dose of ISOT-101
Following Day 7 of SP the average of the daily ReQuest Short Version scores will be used to establish a baseline score to confirm that the subject is experiencing GERD symptoms Any subject who has a ReQuest Short Version RQ average score of 337 90 percentile or ReQuest GI RQ-GI average score 095 on the will be eligible to transition to the Tolerability Phase The ReQuest Short Version SP1-SP7 average and SF-36 will serve as a baseline Investigator will verify eligibility prior to study staff contacting subject
Once eligibility has been verified by the PI the study coordinator will inform subject and confirm that subject wishes to continue in the study Once confirmed study coordinator will
Review concomitant medications
Collect any adverse events
Review calendar for remainder of study
Provide instructions for daily dosing of ISOT-101
Confirm mailing address
Arrange for shipment of 30-day supply of ISOT-101 to the subject There may be up to 7 calendar days between SP Day 7 and TP Day 1 depending on length of time to shipreceive ISOT-101
Tolerability Phase TP
Subjects will take their current GERD therapy as follows
If on PPI therapy QD or BID then the PPI is to be taken as the subject customarily has taken it prior to beginning the study
If on an H-2 antagonist or antacid then the subject may continue these medications as needed throughout the study
All GERD medications and other medications will be recorded daily via the electronic survey
ISOT-101 will be taken daily at bedtime one sachet per day This will be the last thing swallowed prior to bedtime no rinsing and after brushing teeth As the primary endpoint tolerability of ISOT-101 will be assessed In addition changes in the ReQuest Short Version GERD symptom scores RQ RQ-GI and RQ-WSO and SF-36 scores will be assessed for all subjects as well as for the sub-group of subjects that completed all 4 weeks of the protocol Changes in ReQuest symptom scores or SF-36 scores between time point 1 and time point 2 will be the basis of this assessment Further evaluation will include comparison of ISOT-101 tolerability in the 4 subject sub-groups using these two time points
The safety endpoint of the study is to ensure that any adverse events that are reported or observed during the study are appropriately recorded
Study Rationale This is a remote study No office visits required The purpose and efficacy endpoint of this study is to assess whether GERD patients tolerate ISOT-101 In addition usage of the ReQuest validated questionnaire to measure GERD symptoms will be explored as well as usage of the validated SF-36 quality of life QoL questionnaire Each subject serves as hisher own control Relative tolerability in subjects both on and off proton pump inhibitors PPIs will be compared Subjects naïve to PPIs currently taking PPIs and historically on PPIs will be evaluated with ReQuest and QoL scores In addition survey measurements will be taken on a subset of 10 subjects that are non-responders to PPIs These will not be included in the statistical analysis with the above groups A tertiary endpoint of this study is to assess any relevant adverse events that occur
Study Design The test material is ISOT-101 It is an approximately 90 pure maltosyl-isomalto-oligosacchride MIMO prebiotic syrup produced by bacterial fermentationbio-conversion of sucrose and maltose It is taken 1g daily at bedtime
Subjects will have been previously diagnosed with GERD and will fall into one of the following four groups
1 Symptomatic subjects currently not taking PPI therapy and who are naive to PPIs
2 Symptomatic subjects currently not taking PPI therapy who were responsive to prior PPI therapy either QD or BID and who have been off PPIs for at least four weeks
3 Symptomatic subjects currently taking PPI therapy either QD or BID who are partial responders to PPIs
4 10 symptomatic subjects who have had no benefit from PPIs and have not taken PPIs for at least 4 weeks
All subjects will have active GERD symptoms as determined by the ReQuest validated GERD specific questionnaire The study has been designed to have each subject serve as their own control so there will be no placebo arm Each subject will receive ISOT-101 according to the protocol Recruitment for subjects with GERD will be by referrals from GI specialists primary care physicians and general advertising Each candidate will be given information as to how to contact the study coordinator to enroll in the study The goal is to assess 110 subjects after the Screening Phase including the 10 subjects who did not respond to PPIs All subjects will be screened per the eligibility criteria delineated in this protocol by the study coordinator
Two phases have been designed into this study Phase 1 is the Screening Phase SP Phase 2 is the Tolerability Phase TP Subjects will be instructed to take a daily GERD symptom questionnaire the ReQuest Short Version daily throughout the study At five timepoints specific scores will be established for comparison and statistical analysis These timepoints are 1 SP7 - baseline on current therapy if any without ISOT-101 2 TP7 - 1 week on both current therapy if any and ISOT-101 3 TP14 - 2 weeks on both current therapy if any and ISOT-101 4 TP21 - 3 weeks on both current therapy if any and ISOT-101 5 TP28 - 4 weeks on both current therapy if any and ISOT-101 At each of these timepoints subjects will also complete the ReQuest Long Version and the SF-36 Health Survey QoL validated questionnaires They need not complete the ReQuest Short Version on days that the ReQuest Long Version is required Subjects will report any usage of all GERD medications PPI H-2 antagonists antacid throughout their study participation
Enrollment An adequate number of individuals will need to be screened during the Screening Phase using disease specific validated questionnaires to yield approximately 110 qualified subjects to enter and likely complete the Tolerability Phase of the study Recruitment may involve primary care physicians andor gastroenterologists who will make IRB approved study information available to patients who are symptomatic for GERD Such patients will include those partial responders on PPI therapy those who responded to PPIs but have previously stopped their PPI therapy for at least 4 weeks those who are naive to PPI therapy and 10 subjects that have had no benefit from PPIs and have not been on PPI therapy for at least 4 weeks Deviations from the inclusion and exclusion criteria will not be allowed so as not to jeopardize the scientific integrity of the study regulatory acceptability or subject safety Therefore adherence to the criteria as specified in the protocol is essential
All subjects will be required to sign an IRB-approved informed consent or e-consent that complies with the requirements of both 21 CRF Part 50 and Health Insurance Portability and Accountability Act HIPAA before entering the study
The duration of the study is defined for each subject as the date a signed written informed consent or e-consent is provided through Tolerability Phase Day 28 Total participation in study may last up to 8 weeks A comparable gender distribution is sought for the final analysis therefore the ratio of male to female or female to male subjects completing the Tolerability Phase will be capped at 60 of the total
Concomitant Medications and Washout Periods GERD medications Subjects currently taking PPI therapy either QD or BID who are partial responders to PPIs may continue taking PPIs throughout the study as needed Subjects not taking PPIs prior to being enrolled may also take PPIs as needed Antacids or H-2 antagonists may be taken regularly or intermittently as needed throughout the conduct of this study All GERD-related medications taken by the subject should be recorded daily via the daily electronic survey
Prebiotic andor probiotic supplements Enrolled subjects must stop taking all prebiotic andor probiotic supplements 2 weeks prior to entering the Screening Phase of the study Subjects must refrain from taking prebiotic or probiotic supplements through Tolerability Phase Day 28
Sleep medications Enrolled subjects taking medications for sleep disorders must be on a stable dose at time of consent and continue at said dose through Tolerability Phase Day 28
Antibiotics Subjects must not have taken antibiotics within 6 months prior to signing of consent or at any time during their participation in the study If antibiotics are prescribed to the subject during study participation subject must be withdrawn from study and discontinue daily ISOT-101 immediately
All study product sachets used and unused must be returned to Investigator for product accountability
Subject Study Flow Process
No study-related activities will be performed and no subject data will be collected prior to completion of the informed consent process
Screening Phase SP
To enter the SP subjects must have previously been diagnosed with GERD be symptomatic on their current therapy or lack of therapy and fall into one of the 4 study groups noted in Section 40 above The SP will last for 7 days Subjects who do not qualify at any point during the SP will not be allowed to move into the Tolerability Phase TP The TP will last 28 days beginning with first dose of ISOT-101
Following Day 7 of SP the average of the daily ReQuest Short Version scores will be used to establish a baseline score to confirm that the subject is experiencing GERD symptoms Any subject who has a ReQuest Short Version RQ average score of 337 90 percentile or ReQuest GI RQ-GI average score 095 on the will be eligible to transition to the Tolerability Phase The ReQuest Short Version SP1-SP7 average and SF-36 will serve as a baseline Investigator will verify eligibility prior to study staff contacting subject
Once eligibility has been verified by the PI the study coordinator will inform subject and confirm that subject wishes to continue in the study Once confirmed study coordinator will
Review concomitant medications
Collect any adverse events
Review calendar for remainder of study
Provide instructions for daily dosing of ISOT-101
Confirm mailing address
Arrange for shipment of 30-day supply of ISOT-101 to the subject There may be up to 7 calendar days between SP Day 7 and TP Day 1 depending on length of time to shipreceive ISOT-101
Tolerability Phase TP
Subjects will take their current GERD therapy as follows
If on PPI therapy QD or BID then the PPI is to be taken as the subject customarily has taken it prior to beginning the study
If on an H-2 antagonist or antacid then the subject may continue these medications as needed throughout the study
All GERD medications and other medications will be recorded daily via the electronic survey
ISOT-101 will be taken daily at bedtime one sachet per day This will be the last thing swallowed prior to bedtime no rinsing and after brushing teeth As the primary endpoint tolerability of ISOT-101 will be assessed In addition changes in the ReQuest Short Version GERD symptom scores RQ RQ-GI and RQ-WSO and SF-36 scores will be assessed for all subjects as well as for the sub-group of subjects that completed all 4 weeks of the protocol Changes in ReQuest symptom scores or SF-36 scores between time point 1 and time point 2 will be the basis of this assessment Further evaluation will include comparison of ISOT-101 tolerability in the 4 subject sub-groups using these two time points
The safety endpoint of the study is to ensure that any adverse events that are reported or observed during the study are appropriately recorded
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