EPIGUT: EPILEPSY AND GASTROINTESTINAL MICROBIOTA: UNDERSTANDING THERAPY RESPONSE
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,500
- 试验地点
- 6
- 主要终点
- Gut and oral microbiota composition in patients vs. controls
研究概览
简要总结
The goal of this observational study is to learn how the bacteria in the gut and mouth (called the microbiota) are linked to different types of epilepsy and how they may affect how well seizure medicines work.
Researchers want to answer two main questions:
Are certain types of epilepsy linked to changes in the gut or mouth microbiota? Do the bacteria in the gut change how seizure medicines work for each person?
Epilepsy is a brain condition that causes seizures. Even though there are many medicines for epilepsy, some people still have seizures or side effects. Studies in animals show that gut bacteria can raise or lower the chance of seizures. Smaller studies in people suggest the same thing, but they have been limited in size and scope.
In this study, researchers will collect biological samples from people who have newly diagnosed epilepsy and from people without epilepsy (called healthy controls). The samples will be tested to learn which bacteria are present. The researchers will then look for patterns that may explain which types of epilepsy are linked to changes in the microbiota.
The study will also look at whether the bacteria in the gut and mouth affect how well anti-seizure medicines (ASMs) work. For example, the researchers will explore if certain bacteria make medicines work better or worse.
Patients will provide blood, stool and saliva samples. If collected for medical reasons, cerebrospinal fluid (CSF) - the clear liquid that surrounds the brain and spinal cord -will also be used.
Healthy controls will provide stool and saliva samples only
All participants will be asked to fill an online questionnaire to share health and lifestyle information.
Patients also allow researchers to confidentially access data from medical records related to diagnosis and treatment.
By comparing data from many participants across Sweden, researchers hope to understand how gut and mouth bacteria influence epilepsy and seizure control.
This research may help doctors in the future to use a person's microbiota profile to choose the best seizure medicine. The long-term goal is to improve seizure control, reduce side effects, and raise the quality of life for people living with epilepsy.
详细描述
Background:
Clinical studies in humans on the role of the microbiota in promoting seizures and epilepsy are sparse and limited to small, heterogenous cohorts of epileptic patients already treated with ASMs. Larger, treatment-naïve cohorts followed longitudinally are needed to investigate the role of the microbiota in seizures and anti-seizure drug therapy. EpiGUT is building such a cohort in order to study both the oral and gut microbiota by analysis of saliva and fecal samples (primary outcomes). Blood and CSF samples for metabolic and inflammation profiling are collected to analyze how the microbiota may influence systemic and central inflammation and metabolism (secondary outcomes).
In vitro, non-antibiotic drugs can inhibit growth of gut microbes and microbes can metabolize drugs to produce active or toxic metabolites. In vivo, almost nothing is known about the interactions of the microbes and ASMs. Yet these interactions can profoundly influence treatment outcome, as demonstrated for anti-PD1 therapy of patients with cancer as well as for many other treatments of various diseases. It is thus plausible that individual differences in the gut microbiota may be part of the reason why some individuals respond to certain ASMs, and others do not. By confirming this hypothesis and further in vitro validation of specific drug-microbe interactions we can create valuable clinical guidelines for personalizing anti-seizure treatments based on the composition of the gut microbiota, thus increasing the probability of a positive treatment response of the individual patient.
Study design:
EpiGUT studies individuals with newly diagnosed epilepsy and their microbiota in response to different ASMs both on an individual level and in comparison to healthy controls. We will analyze the gut and oral microbial composition and function at baseline, i.e., time of diagnosis and study associations with specific subtypes of epilepsies. Building a unique sample collection of blood and CSF enables mechanistic studies on how specific microbes may modulate seizures through metabolites or inflammatory signaling. We will also study correlations between components of the microbiota and ASM treatment efficacy, as well as drug therapy-associated alterations in the gut microbiota.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Other
入排标准
- 年龄范围
- 2 Years 至 79 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients: Age 2-79 years, newly diagnosed with epilepsy, treatment-naive at time of enrollment
- •Controls: Age 2-79 years
排除标准
- •Patients: already started ASM treatment (more then one dose), has used antibiotics or probiotics in the last three months, has a gastrointestinal diagnosis, has surgically removed parts of the GIT, obesity (BMI>30), T2D, follows a strict exclusion diet, is pregnant or breastfeeding, has a gastrostomy, PEG or jejunostomy
- •Controls: previous epilepsy diagnosis or ASM treatment, has used antibiotics or probiotics in the last three months, has a gastrointestinal diagnosis, has surgically removed parts of the GIT, obesity (BMI>30), T2D, follows a strict exclusion diet, is pregnant or breastfeeding, has a gastrostomy, PEG or jejunostomy
结局指标
主要结局
Gut and oral microbiota composition in patients vs. controls
时间窗: two years after completion of sample collection and sequencing
metagenomic sequencing of home-collected fecal and saliva samples
Changes in gut/oral microbiota in epilepsy patients on monotherapy
时间窗: two years after completion of sample collection and sequencing
Metagenomic sequencing of at home-collected fecal and saliva samples before and after single ASM treatment for approx. three months
次要结局
- Can the gut/oral microbiota at time of diagnosis predict therapy response?(three years after completion of sample collection and sequencing)
- Changes in inflammation markers and metabolites in blood and CSF during monotherapy and in relation to changes in the microbiota(three years after completion of sample collection and sequencing)
研究者
Stefanie P rast-Nielsen
Associate Professor
Karolinska Institutet