Mitochondrial DiseasesNCT03213067
Mitochondrial and Microbiota Relationship
An observational study of Mitochondrial Diseases, run by Newcastle University at 1 site in United Kingdom.
Trial summary
Gastrointestinal (GI) dysmotility in patients with mitochondrial disease are increasingly recognized and often include dysphagia, abdominal pain, abdominal distention, bacterial overgrowth, constipation, and in severe cases surgery. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Diseases
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Apr 2017to 2 Feb 2019
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Mitochondrial diseases are an important group of inherited neurometabolic disorders that invariably exhibit multi-organ involvement, are relentlessly progressive, and result in significant morbidity and mortality. They may manifest as discrete clinical syndromes such as mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes (MELAS), chronic and progressive external ophthalmoplegia (CPEO), and maternally inherited deafness and diabetes (MIDD), or more commonly with a wide overlapping spectrum of clinical features, including hypertrophic cardiomyopathy and gastrointestinal (GI) dysmotility (Gorman et al., 2016; Taylor \& Turnbull, 2005).
Who may be able to join
- Mitochondrial Patients
- Male and Females >18 years at the time of screening
- Patients must have proven genetic disease (confirmed by assessment of heteroplasmy in blood and urine samples) of the m.3243 A>G mutation.
- Capacity to provide informed consent taken before any study related activities.
- Ability and willingness to adhere to the protocol, including all appointments.
- Ability to read and converse in English.
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- Healthy Controls
- Male and Females >18 years at the time of screening
- Capacity to provide informed consent taken before any study related activities.
- Ability and willingness to adhere to the protocol, including all appointments.
- Ability to read and converse in English.
Who cannot join
- Previous history of contraindicated conditions including stroke, brain lesion(s) or tumour.
- Abnormal clinical results as determined by physician.
- Patient without capacity to provide informed consent.
- Patient's unwillingness to adhere to the protocol, including all appointments.
- Language barriers preventing patients from reading and conversing in English.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Grainne Gorman
Newcastle upon Tyne, Tyne and Wear, NE2 4HH
About this study
Official title: Can Metagenomic and Metadata be Combined Using Bioinformatics and Computational Biology Methods to Personalise Patient Treatment.
Gastrointestinal (GI) dysmotility in patients with mitochondrial disease are increasingly recognized and often include dysphagia, abdominal pain, abdominal distention, bacterial overgrowth, constipation, and in severe cases surgery. Although the proposed pathological mechanisms underlying the development of GI dysmotility remain diverse, potential mechanisms include mitochondrial dysfunction of smooth muscle within the GI tract and visceral myopathy. Moreover, bacteria within the GI tract, termed 'gut microbiota' has also been identified as a key contributor towards GI dysmotility.
Aim: The aim of this study is to assess the role that the gut microbiota has on clinical disease expression in patients with mitochondrial disease.
Read more
Objectives: This is a feasibility study to assess:
- How does clinical disease severity impact upon the gut microbiota in mitochondrial patients compared to healthy controls.
- How diagnostic and therapeutic approaches for mitochondrial disease be improved.
Methods: This is a pilot study and is part of the Newcastle Mitochondrial Research Biobank. Stool samples will be collected from patients with a Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes (MELAS) phenotype carrier of the m.3243 A>G mutation (N=20) from the United Kingdom Medical Research Council (MRC) Centre for Mitochondrial Disease Patient Cohort (RES/0211/7552, the largest cohort of mitochondrial patients in the world) and the mitochondrial clinic and age and gender matched healthy controls (N=20). DNA will be extracted from stool samples and the 16S rRNA gene (V4 region) will be sequenced. This data will be analysed using bioinformatics pipelines and computational biology.
Long Term Goal: To generate novel information relating to how the gut microbiota impacts upon clinical disease expression. This information could then be used to build a predictive model designed to optimise diagnosis and therapeutic treatments. This method also holds potential for use as a model for ageing and diseases associated with mitochondria not working properly, such as diabetes, cancer and Parkinson's disease. This research has the potential to reduce costs to the NHS and improve patient care and their quality of life.
Read the detailed description
Background Mitochondrial diseases are an important group of inherited neurometabolic disorders that invariably exhibit multi-organ involvement, are relentlessly progressive, and result in significant morbidity and mortality. They may manifest as discrete clinical syndromes such as mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes (MELAS), chronic and progressive external ophthalmoplegia (CPEO), and maternally inherited deafness and diabetes (MIDD), or more commonly with a wide overlapping spectrum of clinical features, including hypertrophic cardiomyopathy and gastrointestinal (GI) dysmotility. Symptoms arising from gastrointestinal (GI) dysmotility in patients with mitochondrial disease are increasingly recognized and often include dysphagia, abdominal pain, abdominal distention, bacterial overgrowth, constipation, and in severe cases, intestinal pseudo obstruction mimicking an acute surgical abdomen. The high incidence of this was recently confirmed when we surveyed 86 mitochondrial patients about GI symptoms. Sixty five percent of patients experienced GI dysmotility symptoms, including constipation, early satiety, abdominal pain and abdominal distension (under preparation for publication). Although the proposed pathological mechanisms underlying the development of GI dysmotility remain diverse, potential mechanisms include mitochondrial dysfunction of smooth muscle within the GI tract and visceral myopathy. Moreover, bacteria within the GI tract, termed 'gut microbiota' has also been identified as a key contributor towards GI dysmotility.
Rationale To date, there are few effective treatments for patients with mitochondrial disease and those available are predominantly supportive in nature with no proven treatment efficacy, and poor understanding of the links between the gut microbiota, mitochondrial disease, GI dysmotility and patient health and quality of life. Treatments include various antibiotics and laxatives which are generic and not disease specific. Long term effects of drugs are unknown and the impact these have on the GI tract and gut microbiota in mitochondrial disorders are currently unknown. It is essential to optimise supportive therapeutic strategies and design novel modalities to improve clinical management. Although advances in technology now provide more biological information than ever before, the complexity and volume of data generated exceeds the ability to analyse, interpret and translate this information back into the clinical management, highlighting the need to increase clinical analytical capabilities. The use of bioinformatics and computational biology to combine metagenomics data relating to the gut microbiota and metadata (patient characteristics; phenotype/genotype) is one approach to identify and predict what factors, such as drugs, phenotype and genotype, induce gut microbiota dysbiosis.
Elucidating the complexity and workings of the gut microbiota in mitochondrial disease provides a unique approach and deeper understanding of the biology in general, which is currently lacking in primary mitochondrial disorders. This research will contribute to the gut microbiome field and provide a novel insight into the complex microbe:microbe and microbiota-host interactions. The new insights generated here will provide the foundation for interventional studies aimed at manipulating the gut microbiome and relieving disease burden in patients with mitochondrial disease and potentially diseases associated with mitochondrial dysfunction, such as obesity, diabetes and neuro-degenerative disorders such as dementia and Parkinson's disease.
Objectives
The working hypotheses is that patients with mitochondrial disease experience GI dysmotility, and that the gut microbiota accentuates clinical disease severity. This study aims to provide novel information relating to:
- How does clinical disease severity impact upon the gut microbiota in mitochondrial patients compared to healthy controls.
- How diagnostic and therapeutic approaches for mitochondrial disease can be improved.
- Conditions
- Mitochondrial Diseases
- Medical subject headings
- Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Mitochondrial Disease Patients | * Male and Females >18 years at the time of screening * Patients must have proven genetic disease (confirmed by assessment of heteroplasmy in blood and urine samples) of the m.3243 A>G mutation. * Capacity to provide informed consent taken before any study related activities. * Ability and willingness to adhere to the protocol, including all appointments. * Ability to read and converse in English. | |
| Healthy Control Group | * Male and Females >18 years at the time of screening * Capacity to provide informed consent taken before any study related activities. * Ability and willingness to adhere to the protocol, including all appointments. * Ability to read and converse in English. |
What is being measured
The primary outcome is the main question the study is designed to answer.
16S rRNA gene
DNA will be extracted from stool samples and the 16S rRNA gene (V4 region) will be sequenced.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start11 Apr 2017
- Primary completion2 Feb 2019
- Study completion2 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Newcastle University
- Sponsor type
- University, hospital or other
- Collaborators
- Newcastle-upon-Tyne Hospitals NHS Trust
- Responsible party
- Sponsor
- Investigators
- Grainne Gorman, MD, Principal investigator, Consultant Neurologist and Clinical Senior Lecturer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03213067
- Sponsor's protocol ID
- Version 1
- Status last verified
- Jun 2019
- First submitted
- 7 Jul 2017
- Last updated
- 26 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Metagenomic and Metadata be Combined Using Bioinformatics and Computational Biology Methods to Personalise Patient Treatment.
- ClinicalTrials.gov ID
- NCT03213067
- Acronym / sponsor ID
- Version 1
- Conditions
- Mitochondrial Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Newcastle UniversityUniversity, hospital or other
- Collaborators
- Newcastle-upon-Tyne Hospitals NHS Trust
- Study start
- 11 Apr 2017 (actual)
- Primary completion
- 2 Feb 2019 (actual)
- Study completion
- 2 Feb 2019 (actual)
- First posted
- 11 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Gastrointestinal (GI) dysmotility in patients with mitochondrial disease are increasingly recognized and often include dysphagia, abdominal pain, abdominal distention, bacterial overgrowth, constipation, and in severe cases surgery. Although the proposed pathological mechanisms underlying the development of GI dysmotility remain diverse, potential mechanisms include mitochondrial dysfunction of smooth muscle within the GI tract and visceral myopathy. Moreover, bacteria within the GI tract, termed 'gut microbiota' has also been identified as a key contributor towards GI dysmotility.
Aim: The aim of this study is to assess the role that the gut microbiota has on clinical disease expression in patients with mitochondrial disease.
Objectives: This is a feasibility study to assess:
- How does clinical disease severity impact upon the gut microbiota in mitochondrial patients compared to healthy controls.
- How diagnostic and therapeutic approaches for mitochondrial disease be improved.
Methods: This is a pilot study and is part of the Newcastle Mitochondrial Research Biobank. Stool samples will be collected from patients with a Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes (MELAS) phenotype carrier of the m.3243 A>G mutation (N=20) from the United Kingdom Medical Research Council (MRC) Centre for Mitochondrial Disease Patient Cohort (RES/0211/7552, the largest cohort of mitochondrial patients in the world) and the mitochondrial clinic and age and gender matched healthy controls (N=20). DNA will be extracted from stool samples and the 16S rRNA gene (V4 region) will be sequenced. This data will be analysed using bioinformatics pipelines and computational biology.
Long Term Goal: To generate novel information relating to how the gut microbiota impacts upon clinical disease expression. This information could then be used to build a predictive model designed to optimise diagnosis and therapeutic treatments. This method also holds potential for use as a model for ageing and diseases associated with mitochondria not working properly, such as diabetes, cancer and Parkinson's disease. This research has the potential to reduce costs to the NHS and improve patient care and their quality of life.
Detailed description
Background Mitochondrial diseases are an important group of inherited neurometabolic disorders that invariably exhibit multi-organ involvement, are relentlessly progressive, and result in significant morbidity and mortality. They may manifest as discrete clinical syndromes such as mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes (MELAS), chronic and progressive external ophthalmoplegia (CPEO), and maternally inherited deafness and diabetes (MIDD), or more commonly with a wide overlapping spectrum of clinical features, including hypertrophic cardiomyopathy and gastrointestinal (GI) dysmotility. Symptoms arising from gastrointestinal (GI) dysmotility in patients with mitochondrial disease are increasingly recognized and often include dysphagia, abdominal pain, abdominal distention, bacterial overgrowth, constipation, and in severe cases, intestinal pseudo obstruction mimicking an acute surgical abdomen. The high incidence of this was recently confirmed when we surveyed 86 mitochondrial patients about GI symptoms. Sixty five percent of patients experienced GI dysmotility symptoms, including constipation, early satiety, abdominal pain and abdominal distension (under preparation for publication). Although the proposed pathological mechanisms underlying the development of GI dysmotility remain diverse, potential mechanisms include mitochondrial dysfunction of smooth muscle within the GI tract and visceral myopathy. Moreover, bacteria within the GI tract, termed 'gut microbiota' has also been identified as a key contributor towards GI dysmotility.
Rationale To date, there are few effective treatments for patients with mitochondrial disease and those available are predominantly supportive in nature with no proven treatment efficacy, and poor understanding of the links between the gut microbiota, mitochondrial disease, GI dysmotility and patient health and quality of life. Treatments include various antibiotics and laxatives which are generic and not disease specific. Long term effects of drugs are unknown and the impact these have on the GI tract and gut microbiota in mitochondrial disorders are currently unknown. It is essential to optimise supportive therapeutic strategies and design novel modalities to improve clinical management. Although advances in technology now provide more biological information than ever before, the complexity and volume of data generated exceeds the ability to analyse, interpret and translate this information back into the clinical management, highlighting the need to increase clinical analytical capabilities. The use of bioinformatics and computational biology to combine metagenomics data relating to the gut microbiota and metadata (patient characteristics; phenotype/genotype) is one approach to identify and predict what factors, such as drugs, phenotype and genotype, induce gut microbiota dysbiosis.
Elucidating the complexity and workings of the gut microbiota in mitochondrial disease provides a unique approach and deeper understanding of the biology in general, which is currently lacking in primary mitochondrial disorders. This research will contribute to the gut microbiome field and provide a novel insight into the complex microbe:microbe and microbiota-host interactions. The new insights generated here will provide the foundation for interventional studies aimed at manipulating the gut microbiome and relieving disease burden in patients with mitochondrial disease and potentially diseases associated with mitochondrial dysfunction, such as obesity, diabetes and neuro-degenerative disorders such as dementia and Parkinson's disease.
Objectives
The working hypotheses is that patients with mitochondrial disease experience GI dysmotility, and that the gut microbiota accentuates clinical disease severity. This study aims to provide novel information relating to:
- How does clinical disease severity impact upon the gut microbiota in mitochondrial patients compared to healthy controls.
- How diagnostic and therapeutic approaches for mitochondrial disease can be improved.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mitochondrial Disease Patients | – | –* Male and Females >18 years at the time of screening * Patients must have proven genetic disease (confirmed by assessment of heteroplasmy in blood and urine samples) of the m.3243 A>G mutation. * Capacity to provide informed consent taken before any study related activities. * Ability and willingness to adhere to the protocol, including all appointments. * Ability to read and converse in English. |
| Healthy Control Group | – | –* Male and Females >18 years at the time of screening * Capacity to provide informed consent taken before any study related activities. * Ability and willingness to adhere to the protocol, including all appointments. * Ability to read and converse in English. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Mitochondrial diseases are an important group of inherited neurometabolic disorders that invariably exhibit multi-organ involvement, are relentlessly progressive, and result in significant morbidity and mortality. They may manifest as discrete clinical syndromes such as mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes (MELAS), chronic and progressive external ophthalmoplegia (CPEO), and maternally inherited deafness and diabetes (MIDD), or more commonly with a wide overlapping spectrum of clinical features, including hypertrophic cardiomyopathy and gastrointestinal (GI) dysmotility (Gorman et al., 2016; Taylor \& Turnbull, 2005).
Key inclusion criteria (11 listed)
- Mitochondrial Patients
- Male and Females >18 years at the time of screening
- Patients must have proven genetic disease (confirmed by assessment of heteroplasmy in blood and urine samples) of the m.3243 A>G mutation.
- Capacity to provide informed consent taken before any study related activities.
- Ability and willingness to adhere to the protocol, including all appointments.
Key exclusion criteria (5 listed)
- Previous history of contraindicated conditions including stroke, brain lesion(s) or tumour.
- Abnormal clinical results as determined by physician.
- Patient without capacity to provide informed consent.
- Patient's unwillingness to adhere to the protocol, including all appointments.
- Language barriers preventing patients from reading and conversing in English.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
16S rRNA gene
Time frame: 6 months
DNA will be extracted from stool samples and the 16S rRNA gene (V4 region) will be sequenced.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Grainne Gorman, MD principal investigator
Consultant Neurologist and Clinical Senior Lecturer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mitochondrial Diseases, run by Newcastle University at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
16S rRNA gene (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2019.