Multi-Center Study of Panosyl-Isomaltooligosaccharides Adjunctive to PPI Therapy to Treat GERD
Study Details
Study Description
Brief Summary
This study will be conducted as a multi-center, randomized, double-blind, placebo-controlled trial to evaluate the effect of MHS-1031 on heartburn symptom-free days in two similar subject groups with GERD-related heartburn symptoms.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
MHS-1031 is a specific proprietary digestion-resistant oligosaccharide carbohydrate that serves as a prebiotic. The active ingredient in MHS-1031 is a well-defined and well-characterized distribution of panosyl-isomaltooligosaccharides (PIMOs) ranging in degree of polymerization (DP) from DP3 to DP8.
All candidate subjects must be at least partial responders to daily proton pump inhibitor (PPI) acid suppressive therapy. Candidate subjects will be screened for medical history of chronic heartburn that may be associated with other medical conditions, and these subjects will be excluded.
Two groups will be studied: those responsive to proton pump inhibitors (PPI-R) and those partially responsive to proton pump inhibitors (PPI-PR). Subjects will undergo a baseline screening phase of two weeks (PPI-PR and PPI-R) (Screening Phase [SP]) followed by eight weeks of treatment with MHS-1031 (1 g/day) or placebo (Treatment Phase [TP]).
The primary objective of this study is to evaluate the effect of daily MHS-1031 administration adjunctive to PPI therapy on change in GERD-related heartburn symptom-free days Efficacy will be assessed using patient reported outcome (PRO) questionnaires, concomitant medication assessments, and assessment of adverse events For the PPI-R group, efficacy will be determined based on the difference between baseline weekly average heartburn symptom-free days and weekly average heartburn symptom-free days at the end of Treatment Phase Week 8 (as measured using the Reflux Disease Questionnaire Electronic Diary). Scores range from 0 (never) to 4 (very often); higher score indicates a worse outcome.
For the PPI-PR group, efficacy will be determined based on the difference between baseline weekly average heartburn symptom-free days and weekly average heartburn symptom-free days at the end of Treatment Phase Week 8 (as measured using the Reflux Disease Questionnaire Electronic Diary). Scores range from 0 (never) to 4 (very often); higher score indicates a worse outcome.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Proton Pump Inhibitor (PPI) Partial Responders - Drug Product Panosyl-isomaltooligosaccharide (PIMO) liquid 1 g (1.5 ml) per day for 8 weeks |
Drug: MHS-1031
Study medication will be supplied as a syrup in individual sachets containing 1g (1.5 mL) of MHS-1031. Subjects will be randomized in 2:1 fashion to either study drug (2) or placebo (1)
Other Names:
|
| Placebo Comparator: Proton Pump Inhibitor (PPI) Partial Responders - Placebo Placebo liquid (1.5 ml) per day for 8 weeks |
Other: Placebo
Matching placebo is an oral solution formulated to have a degree of sweetness and acidity similar to the study medication and will be provided in equivalent sachets containing 1.5g (1.5 mL) of the oral placebo solution.
|
| Active Comparator: Proton Pump Inhibitor (PPI) Responders - Drug Product Panosyl-isomaltooligosaccharide (PIMO) liquid 1 g (1.5 ml) per day for 8 weeks |
Drug: MHS-1031
Study medication will be supplied as a syrup in individual sachets containing 1g (1.5 mL) of MHS-1031. Subjects will be randomized in 2:1 fashion to either study drug (2) or placebo (1)
Other Names:
|
| Placebo Comparator: Proton Pump Inhibitor (PPI) Responders - Placebo Placebo liquid (1.5 ml) per day for 8 weeks |
Other: Placebo
Matching placebo is an oral solution formulated to have a degree of sweetness and acidity similar to the study medication and will be provided in equivalent sachets containing 1.5g (1.5 mL) of the oral placebo solution.
|
Outcome Measures
Primary Outcome Measures
- Heartburn free days [8 weeks]
The difference between baseline weekly average heartburn symptom-free days and weekly average heartburn symptom-free days at the end of Treatment Phase Week 8 (as measured using the Reflux Disease Questionnaire Electronic Diary). Scores range from 0 (never) to 4 (very often); higher score indicates a worse outcome.
Secondary Outcome Measures
- Heartburn symptom severity [8 weeks]
The difference between baseline weekly average heartburn symptom severity score and weekly average heartburn symptom severity score at the end of Treatment Phase Week 8 (as measured using the Reflux Disease Questionnaire Electronic Diary). Scores range from 0 (did not have) to 5 (severe); higher score indicates a worse outcome.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Ability to participate in the study, undergo all protocol activities, communicate in English, and provide signed informed consents.
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Ability to complete all required online Daily RESQ-eD questionnaires, daily medication questionnaires (Screening Phase 2-Week Assessment and Treatment Phase), 4-item Patient Health Questionnaire for Depression and Anxiety (PHQ-4) questionnaire (which is Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder 2-item (GAD-2) questionnaires combined on one form) (Screening Phase 2-Week Assessment Day 14), and monthly Participant Global Assessment questionnaire (Treatment Phase).
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Access to a computer/tablet/phone with internet access and active email account in order to complete online questionnaires daily throughout study participation.
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Males or females between ≥ 18 and ≤ 75 years of age, with a BMI ≥ 19 and < 35 kg/m2.
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Female subjects must be postmenopausal or surgically sterile or, if of childbearing potential, must agree to use a medically acceptable form of contraception from the time of signing the informed consent forms through completion of study. If only the barrier method is used, a single barrier or better is adequate. Postmenopausal women must have had ≥ 12 months of spontaneous amenorrhea. Surgically sterile women are defined as those who have had a hysterectomy, bilateral ovariectomy, or bilateral tubal ligation. All women of childbearing potential must have a negative pregnancy test result before administration of study drug.
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Must be on stable doses of medications, if any, prescribed for chronic conditions other than GERD.
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Subject must be taking PPI, once daily (qd) (defined as 5-7 days/week on average) at no more than the dosing listed in the table below, for at least four consecutive weeks with symptom improvement (frequency and/or severity) prior to the Screening Call selected from the following list of medications: omeprazole (20 mg), esomeprazole (20 mg), lansoprazole (30 mg), dexlansoprazole (30 mg), pantoprazole (40 mg), rabeprazole (20 mg)
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History of a minimum of 3 months of GERD-related heartburn symptoms (i.e., "burning feeling behind the breastbone" and/or "pain behind your breastbone" and/or "heartburn" per questions 1, 2 or 3 of RESQ-eD) with the following frequency: PPI-PR: ≥ 3 days/week on average during the prior 3 months and during the 2-Week Screening Assessment; PPI-R: <3 days/week on average during the prior 3 months, and during the 2-Week Screening Assessment
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[PPI-PR] Endoscopy within the prior 90 days performed either on or off PPIs, and confirmation that self-reported GERD-related heartburn symptoms improved while taking daily PPI.
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Subject has maintained a stable diet for ≥ 30 days prior to the Screening Call and is willing to maintain that diet for the duration of the study (ie, if subject is currently following diets including, but not limited to, Keto, FODMAP, Vegan, Vegetarian, s/he must be willing to continue this dietary lifestyle through end-of-study visit).
Exclusion Criteria:
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Any PPI dosing other than once daily (qd), per the table listed above. For this study PPI qd is defined at 5-7 days/week on average.
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Taking more than one type of PPI.
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Current use of any mouthwash (e.g., Listerine, Scope, others) or unwilling to discontinue use for the duration of the study (requires 3-day washout prior to starting the 2-Week Screening Assessment, and discontinued use for the duration of all phases of the study).
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Current use of histamine 2 receptor antagonists (H2Ras) and unwilling to discontinue use for the duration of the study 2-Week Screening Assessment (requires 7-day washout prior to starting the 2-Week Screening Assessment).
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Surgical procedure requiring general anesthesia within 60 days of the Screening Call.
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Colonoscopy in the past 30 days, or scheduled for colonoscopy at any time for the duration of the study, and unwilling to postpone until after study completion.
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History of cancer diagnosis and/or treatment (other than basal cell carcinoma of the skin) within the preceding five years.
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Concomitant illness with potential to confound outcome assessments for this study, including, but not limited to: History of untreated peptic or gastric ulcer, Zollinger-Ellison syndrome, or Helicobacter pylori (H. pylori) positivity without a history of successful treatment; History of ulcerative colitis, Crohn's disease, colon cancer, current stomach ulcers, pancreaticobiliary disorders (e.g., gallstones, bile duct stones, pancreatic stones, pancreatitis), diverticulitis
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History of acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection.
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Significant morbidity of the heart, kidney, liver or lung.
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History of Long QT Syndrome
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History of Torsades de pointes (TdP)
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Neuropsychiatric disorder.
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Known or suspected alcoholism, drug addiction, or significant drug abuse within 1 year of the Screening Call based on subject reporting and PI assessment.
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Active history of tobacco or nicotine use (of any type) in the last 6 months.
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Alcohol abuse (for alcohol defined as: > 14 drinks/week or 4 drinks/day for men, >7 drinks/week or 3 drinks/day for women).
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Use of cannabis (all forms) of > 2 days/week on average.
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Any known medical condition, clinical signs and symptoms, vital signs, abnormal laboratory, or other testing, considered clinically significant by the Principal Investigator (PI), that could interfere with the subject's participation in and completion of the study including, but not limited to: Uncontrolled hypertension; Diabetes uncontrolled by diet (i.e., requiring oral medication or insulin); Previous anaphylactic reaction to any medication; History of adrenal disease, diabetic nephropathy, or gastroparesis; Uncontrolled hypothyroidism; Untreated mental disorder; Spinal cord injury
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History of severe drug allergy (or hypersensitivity), or known hypersensitivity to the investigational product.
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Cerebrovascular event (stroke) or myocardial infarction (MI) within the last 6 months.
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Structural abnormality of the gastrointestinal (GI) tract, or disease or condition that can affect GI motility, or defecation.
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Planned travel outside the USA during the study period.
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History or presence of pseudo-obstruction, colon cancer, malignant polyps, colitis, ischemic colitis, abdominal adhesions, intestinal ischemia, esophageal atresia, laxative or enema abuse, or pelvic floor dysfunction.
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Current COVID19 infection, or a history of a prior COVID19 infection with ongoing symptoms suggestive of "Long COVID".
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History of scleroderma, Barrett's esophagus, esophageal cancer, esophageal stricture or scarring.
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History of endoscopically determined erosive esophagitis of classes LA grade B through
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Known hiatal hernia > 2 cm.
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History of surgery or endoscopic treatment including fundoplication and/or dilation for esophageal stricture.
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History of gastric surgery (except for endoscopic removal of benign polyps) or bariatric surgery.
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Use of a barium enema within 30 days of the Screening Call.
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History of fecal impaction that required hospitalization or emergency room treatment within 3 months of the Screening Call.
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History of eating disorder within the last 5 years.
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History of substantiated (documented by computed tomography (CT) scan or hospitalization) diverticulitis, or any ongoing chronic condition (eg, polycystic kidney disease, endometriosis, ovarian cysts, or other) that may be associated with chronic abdominal pain or discomfort and might confound the assessments in this study during the 2 years prior to the Screening Call.
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Surgical history meeting any of the following criteria: Gastric bypass surgery or invasive procedure for the treatment of obesity or surgery to remove a segment of the GI tract at any time prior to the Screening Call; Gastric band present within the past 60 days; Open surgery of the abdomen, pelvis, or retroperitoneal structures within 6 months prior to the Screening Call; Laparoscopic appendectomy or cholecystectomy or other instrumentation of the bowel < 60 days prior to the Screening Call.
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Prior use of the study medication MHS-1031
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Use of any of the following dietary supplements: Prebiotin Prebiotic, ISOThrive Prebiotic Nectar, Bimuno.
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Use of fructo-oligosaccharides (FOS) or inulin.
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History of diseases that have symptoms that may be confused with GERD (i.e., "burning feeling behind the breastbone" and/or "pain behind your breastbone" and/or "heartburn" per RESQ-eD questions 1, 2, or 3): eosinophilic esophagitis, angina, esophageal spasm, achalasia, rumination, or other conditions involving the mouth and/or throat, dysphagia, or dyspnea.
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Taking any excluded medications listed in the protocol.
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Antibiotic use within 60 days of the Screening Call.
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Pregnancy, lactation, planned pregnancy or planned ova donation during the study period.
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Use of colon prep or high colonic within 30 days prior to the Screening Call.
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Narcotic (e.g., opiate) use within 60 days of the Screening Call.
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Use of any investigational product within 3 months prior to the Screening Call.
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Participation in another investigation (clinical trial) during the course of this study.
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Participation in a rigorous weight loss program.
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Any major lifestyle change, such as getting married, change in residence, change in job, or other highly stressful event planned during the study period.
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Diagnosis of, irritable bowel syndrome (IBS-D and IBS-C), Chronic Idiopathic Constipation.
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Daily use of PPIs without significant improvement of heartburn symptoms.
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Self or relative employed directly or indirectly by the Sponsor or relative or employee of investigator or investigator's staff.
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Other conditions or situations that, in the Principal Investigator's opinion, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Microbiome Health Sciences
- VBHRC Virginia Catalyst
Investigators
- Principal Investigator: Peter Swann, MD, Microbiome Health Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MHS-1031-04