Open Label Tolerability Study of a Novel Microbiome Therapeutic (ISOT-101), Maltosyl-Isomalto-oligosaccharides (MIMO), in Subjects With Gastroesophageal Reflux Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 156
- 试验地点
- 2
- 主要终点
- Tolerability of ISOT-101 using GERD ReQuest Short Version
研究概览
简要总结
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 his/her 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.
详细描述
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 don't 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, Barrett's 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 his/her 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 fermentation/bio-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:
- Symptomatic subjects currently not taking PPI therapy and who are naive to PPIs.
- 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.
- Symptomatic subjects currently taking PPI therapy (either QD or BID) who are partial responders to PPIs.
- 10 symptomatic subjects who have had no benefit from PPIs and have not taken PPIs for at least 4 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •English-speaking male and female adults between the ages of 25 and 75, inclusive
- •Body mass index (BMI) <35 and >19
- •Either 3.a. or 3.b. or both, based on the Screening Phase ReQuest Short and Long Version responses:
- •At least one incidence of (a) acid complaints; (b) upper abdominal/stomach complaints and RQ Total score >3.37 or RQ-GI score >0.95
- •Four days or more of combined incidence of (a) acid complaints; (b) upper abdominal/stomach complaints.
- •History (minimum of three months) of GERD symptoms as defined in #3 above
- •Must be on stable doses of medications, if any, prescribed for chronic conditions other than GERD
- •If female, must be on an active contraceptive measure or have male partner(s) with suitable protective measures
- •Have access to a computer/tablet/phone with internet access and active e-mail account in order to complete electronic surveys daily throughout study participation
- •Ability and willingness to give consent to participate in study
排除标准
- •Significant comorbidities that are not medically stable
- •History of scleroderma, diabetes, Barrett's esophagus, esophageal cancer, esophageal stricture, or esophageal scarring (fibrosis)
- •Known hiatal hernia > 2cm
- •Positive diagnosis for Helicobacter pylori (HP) or has had an HP infection within 45 days of study entry
- •History of surgery or endoscopic treatment including fundoplication and dilation for esophageal stricture
- •History of gastric surgery (except for endoscopic removal of benign polyps) or bariatric surgery
- •BMI >=35, BMI <=19
- •History of diseases that have symptoms that may be confused with GERD, such as eosinophilic esophagitis, angina, gastritis, esophageal spasm, rumination, or other conditions involving the mouth, throat, chest or abdomen
- •Active history of nicotine use, cannabis use or alcohol abuse (as defined by: greater than 14 drinks/week or 4 drinks/day for men, 7 drinks/week or 3 drinks/day for women). Has used any tobacco, nicotine or cannabis products in the last 6 months or has abused alcohol in the last 6 months
- •Taking any excluded medications listed in the protocol (e.g. metformin, antibiotics within the prior 6 months.)
- •If female, is pregnant, lactating, or intending to become pregnant before, during or within 4 weeks after participating in this study or intending to donate ova during such time period
- •Primary sleep disorder including sleep apnea, restless leg syndrome, or insomnia
- •Colon prep within 30 days prior to study entry
- •Use of any investigational product within 90 days prior to study entry
- •Participation in another investigation (clinical trial) during the course of this study
- •Participation in a rigorous weight loss program or have any planned changes in diet or lifestyle, such as getting married, change in residence, change in job, or other highly stressful event
- •Diagnosis of inflammatory bowel disease, irritable bowel syndrome, or chronic diarrhea (mild chronic constipation is allowed)
- •Employment (or relative of an employee) or involvement in any way with ISOThrive Inc.
- •An investigator, key study personnel or first degree relative of anyone involved with the study
- •Other conditions or situations that, in the 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
结局指标
主要结局
Tolerability of ISOT-101 using GERD ReQuest Short Version
时间窗: 4 weeks
Assess whether symptomatic GERD patients tolerate ISOT-101 by measuring the differences in baseline and post-intervention score using GERD ReQuest Short Version. The scores for weeks 1, 2, 3, and 4 will be compared with baseline. With regard to the ReQuest Short Version questionnaire, the range is 0 to 46.28 with higher numbers reflecting more severe symptoms. Tolerability is defined as the post-intervention score is equal to or less than baseline.
Tolerability of ISOT-101 using GERD ReQuest Long Version
时间窗: 4 weeks
Assess whether symptomatic GERD patients tolerate ISOT-101 by measuring the differences in baseline and post-intervention scores using GERD ReQuest Long Version. The scores for weeks 1, 2, 3, and 4 will be compared with baseline. With regard to the ReQuest Long Version, the range is 0 to 46.28 with higher numbers reflecting more severe symptoms. Tolerability is defined as the post-intervention score is equal to or less than baseline.
Tolerability of ISOT-101 using Rand Short Form-36 (v1.0)
时间窗: 4 weeks
Assess whether symptomatic GERD patients tolerate ISOT-101 by measuring the differences in baseline and post-intervention scores using Rand Short Form-36 (v1.0). The scores for weeks 1, 2, 3, and 4 will be compared with baseline. The range of the SF-36 scoring is 0-100 with higher numbers defining a more favorable health state. Tolerability is defined as the post-intervention score is equal to or greater than baseline.
次要结局
- Measure adverse events(4 weeks)