Low Residue Diet Study in Mitochondrial Disease (LRD)
Primary Purpose
Mitochondrial Diseases
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Low Residue Diet Intervention
Sponsored by
About this trial
This is an interventional treatment trial for Mitochondrial Diseases focused on measuring Dysmotility, Microbiome, Transit Time, Gastrointestinal
Eligibility Criteria
Inclusion Criteria:
- Male or female, aged 18 and over.
- Genetic or biochemical confirmation of mitochondrial disease.
- ROME III criteria of constipation (Appendix 2).
- Stable gastrointestinal drug regimen prior to commencement of study, at least 3 months prior study inclusion.
- No known hypersensitivities to any of the ingredients in the preparations.
- Not already implementing a low residue diet.
- Competent to make such decisions in the opinion of the investigator.
- Females of child bearing age require a negative pregnancy test.
Exclusion Criteria:
- Patients with known allergies to any adjuncts in the dietary preparation
- Patients with bowel obstruction
- Females who are pregnant, lactating or planning a pregnancy.
- Planned surgery during the course of the trial.
- Participation in another drug trial concurrently or in the preceding 12 weeks.
- Any condition which would put the participant at risk if they were to take part in the trial.
Sites / Locations
- Grainne Gorman
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment Group
Arm Description
This is a single arm study where forty patients with a genetically or biochemically proven diagnosis of mitochondrial disease will be recruited from the mitochondrial CRESTA clinic and / or Medical Research Council Mitochondrial Disease Patient Cohort Study in Newcastle. All forty patients will be assessed prior to and following a 12 week low residue diet study intervention.
Outcomes
Primary Outcome Measures
Assess tolerability of a Low Residue Diet (LRD) in mitochondrial patients
Tolerability of the LRD will be assessed using food diaries
Stool Frequency and consistency
Assess stool consistency according to the Bristol Stool Form scale. Patients will select from the following to describe their stool consistency:
Type 1: Separate hard lumps, like nuts Type 2: Sausage-like but lumpy Type 3: Like a sausage but with cracks in the surface Type 4: Like a sausage or snake, smooth and soft Type 5: Soft blobs with clear-cut edges Type 6: Fluffy pieces with ragged edges, a mushy stool Type 7: Watery, no solid pieces
Secondary Outcome Measures
Gastrointestinal Dysmotility
To determine the impact of a LRD on GI dysmotility symptoms using Assessment of Constipation-Symptom (PAC-SYM) questionnaire.
Disease Burden
To determine the effect of LRD on patients Disease burden as assessed by the Newcastle Mitochondrial Disease Adult Scale (NMDAS) disease burden and quality of life. This is a questionnaire developed and validated by Wellcome Centre for Mitochondrial Research, Newcastle upon Tyne. This is a scored questionnaire that encompasses questions on patient's disease burden encompassing:
Current Function: Vision with usual glasses or contact lenses; Migraine Headaches; Seizures; Stroke like episodes; Encephalopathic Episodes; Gastro-intestinal symptoms; Diabetes mellitus; Respiratory muscle weakness and Cardiovascular system.
Current Clinical Assessment: Visual acuity; Ptosis; Chronic Progressive External Ophthalmoplegia; Dysphonia/Dysarthria; Myopathy; Cerebellar ataxia; Neuropathy; Pyramidal Involvement; Extrapyramidal and Cogitation.
These are all included under the NMDAS questionnaire and are used by clinical care teams to help determine patient's current disease burden.
Gut Microbiome changes
Assess effect of a LRD on gut metagenomics
Gut Microbiome Comparison
A comparison of the gut microbiome composition and diversity assessed by sequencing, between healthy controls and mitochondrial patients prior to the LRD intervention.
Food Intake
To assess the impact of a LRD on food intake (Food Frequency Questionnaire (FFQ) will be completed for 72 hours (1 day over the weekend and 2 days during the week).
Colonic Transit Time
Colonic transit time (CTT) as assessed by plain abdominal X-ray following ingestion of oral colonic marker ingestion.
Physical Activity
Activity level (GeneActiv 7-10 days).
Biochemistry
The Biochemistry department in the Royal Victoria Infirmary in Newcastle upon Tyne will be provided with whole blood. Using this they will measures liver enzymes (alanine transaminase, aspartate aminotransferase, gamma-glutamyl transpeptide), alkaline phosphatase, albumin, bilirubin, lipid profile and C-Peptide tests.
Gastrointestinal Health
To determine the impact of a LRD on patient GI symptoms using the Gastrointestinal Quality-of-Life Index. This includes defecation characteristics including laxative use and reported abdominal symptoms categorized as pain or cramps and bloating or flatulence according to five classifications (1, none; 2, mild; 3, moderate; 4, severe; or 5, very severe).
Anthropometrics
Weight (kg)
Physical Measurements
Body Mass Index
Physical Dimensions
Waist to hip ratio (inches)
Haematology
The Haematology department in the Royal Victoria Infirmary in Newcastle upon Tyne will be provided with whole blood. Using this they will provide a Full blood count, Haematocrit screen, Ferritin, Vitamin B12, HbA1c and Folate.
Full Information
NCT ID
NCT03388528
First Posted
October 27, 2017
Last Updated
October 9, 2019
Sponsor
Newcastle University
Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
1. Study Identification
Unique Protocol Identification Number
NCT03388528
Brief Title
Low Residue Diet Study in Mitochondrial Disease
Acronym
LRD
Official Title
Phase II Feasibility Study of the Efficacy and Acceptability of a Low Residue Diet in Adult Patients With Mitochondrial Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
September 8, 2017 (Actual)
Primary Completion Date
February 7, 2019 (Actual)
Study Completion Date
February 7, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Newcastle University
Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Slow movement of patients guts is referred to as intestinal dysmotility, and is increasingly recognised as a debilitating manifestation of mitochondrial disease both in adults and children.
To date, symptoms of slow gut movements have been managed with laxatives and drugs that increase movement of the guts with variable results. A low residue diet is a form of low fibre diet (<10g fibre per day) that is used to minimise symptoms of poor movement of the guts. This reduces fecal volume and bulk, and hence gut workload, ensuring limited bowel activity and colonic rest. It has been shown to be well accepted in other conditions associated with slow gut movements. However, its role in patients with mitochondrial disease is unknown. The investigators are particularly interested in:
Does a low residue diet (low fibre) cause a change in the number of stools per week and stool consistency?
Is a low residue diet tolerated well and easy to comply with?
Does a low residue diet reduce gut symptoms of abdominal pain, bloating, and constipation?
Does a low residue diet improve quality of life and disease burden?
Does a low residue diet affect the bacteria in the gut?
Can we prove by X-ray that movement of food through the gut is slowed in patients with mitochondrial disease, and whether a low residue diet alters the speed of movement of food through the gut?
Can a low residue diet change patients physical activity levels?
Does a low reside diet change dietary patterns and food intake?
Does a low residue diet alter anthropometrics, such as weight, body mass index and waist to hit ratio?
Can a low residue diet improve kidney and liver function and lipid profile in blood samples?
The investigators hope that by looking at these areas that a low residue diet may be able to improve patients slow gut movements, health, quality of life and disease burden.
Detailed Description
Intestinal dysmotility is increasingly recognised as a debilitating manifestation of mitochondrial disease both in adults and children (1). It is a frequent symptom of other neurological conditions including Cerebral Palsy, Multiple Sclerosis and Parkinson's Disease. Symptoms of intestinal dysmotility are often overlooked and frequently under-diagnosed in its early stages.
Indeed, in its most severe form, intestinal dysmotility may manifest as intestinal pseudo obstruction (IPO), characterised by a clinical picture suggestive of mechanical obstruction, exemplifying the need for early detection and management. To date, symptoms of intestinal dysmotility in slow transit time constipation, limited fluid and calorie intake, weight loss, and small intestinal bacterial overgrowth and in severe cases intestinal pseudo obstruction (2, 3). Moreover, the bacteria that reside within the gastrointestinal (GI) tract compete for nutrients, contributing to weight loss due to malabsorption of fat (4), protein and carbohydrates (5, 6), vitamin (7-11) and iron deficiency (12) are often evident. Further problems include poor digestion and absorption food, an impaired immune system, and an impaired drug absorption ability, all of which influence patient health, quality of life and increases National Health Service (NHS) costs.
A low residue diet is a form of low fibre diet (<10g fibre per day) that is used to minimise symptoms of intestinal dysmotility by reducing faecal volume and bulk and hence bowel workload, ensuring limited bowel activity and colonic rest. It has been shown to be both tolerable and efficacious in other conditions associated with intestinal dysmotility; however, its role in patients with mitochondrial disease and intestinal dysmotility, is unknown.
This feasibility study proposes to systematically gather data on whether a low residue diet is tolerable and has an effect on intestinal dysmotility and health-related quality of life in in patients with mitochondrial disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitochondrial Diseases
Keywords
Dysmotility, Microbiome, Transit Time, Gastrointestinal
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Forty patients with a genetically or biochemically proven diagnosis of mitochondrial disease will be recruited from the mitochondrial Clinics for Research and Service in Themed Assessments (CRESTA) clinic and / or Medical Research Council Mitochondrial Disease Patient Cohort Study in Newcastle
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment Group
Arm Type
Experimental
Arm Description
This is a single arm study where forty patients with a genetically or biochemically proven diagnosis of mitochondrial disease will be recruited from the mitochondrial CRESTA clinic and / or Medical Research Council Mitochondrial Disease Patient Cohort Study in Newcastle. All forty patients will be assessed prior to and following a 12 week low residue diet study intervention.
Intervention Type
Dietary Supplement
Intervention Name(s)
Low Residue Diet Intervention
Intervention Description
All patients will be provided with a LRD plan (< 10g fibre per day) for 12 weeks between visits 2 and 3. They will also be supplemented with multivitamin and mineral tablet or liquid (Forceval) to meet nutrient requirements (prescribed as standard care). The dietitian will provide written and oral information about the LRD and weekly telephone calls to assess patient's progress on the diet.
Primary Outcome Measure Information:
Title
Assess tolerability of a Low Residue Diet (LRD) in mitochondrial patients
Description
Tolerability of the LRD will be assessed using food diaries
Time Frame
Change from baseline to 12 weeks
Title
Stool Frequency and consistency
Description
Assess stool consistency according to the Bristol Stool Form scale. Patients will select from the following to describe their stool consistency:
Type 1: Separate hard lumps, like nuts Type 2: Sausage-like but lumpy Type 3: Like a sausage but with cracks in the surface Type 4: Like a sausage or snake, smooth and soft Type 5: Soft blobs with clear-cut edges Type 6: Fluffy pieces with ragged edges, a mushy stool Type 7: Watery, no solid pieces
Time Frame
Change from baseline to 12 weeks
Secondary Outcome Measure Information:
Title
Gastrointestinal Dysmotility
Description
To determine the impact of a LRD on GI dysmotility symptoms using Assessment of Constipation-Symptom (PAC-SYM) questionnaire.
Time Frame
Change from baseline to 12 weeks
Title
Disease Burden
Description
To determine the effect of LRD on patients Disease burden as assessed by the Newcastle Mitochondrial Disease Adult Scale (NMDAS) disease burden and quality of life. This is a questionnaire developed and validated by Wellcome Centre for Mitochondrial Research, Newcastle upon Tyne. This is a scored questionnaire that encompasses questions on patient's disease burden encompassing:
Current Function: Vision with usual glasses or contact lenses; Migraine Headaches; Seizures; Stroke like episodes; Encephalopathic Episodes; Gastro-intestinal symptoms; Diabetes mellitus; Respiratory muscle weakness and Cardiovascular system.
Current Clinical Assessment: Visual acuity; Ptosis; Chronic Progressive External Ophthalmoplegia; Dysphonia/Dysarthria; Myopathy; Cerebellar ataxia; Neuropathy; Pyramidal Involvement; Extrapyramidal and Cogitation.
These are all included under the NMDAS questionnaire and are used by clinical care teams to help determine patient's current disease burden.
Time Frame
Change from baseline to 12 weeks
Title
Gut Microbiome changes
Description
Assess effect of a LRD on gut metagenomics
Time Frame
Change from baseline to 12 weeks
Title
Gut Microbiome Comparison
Description
A comparison of the gut microbiome composition and diversity assessed by sequencing, between healthy controls and mitochondrial patients prior to the LRD intervention.
Time Frame
Baseline only (prior to any intervention)
Title
Food Intake
Description
To assess the impact of a LRD on food intake (Food Frequency Questionnaire (FFQ) will be completed for 72 hours (1 day over the weekend and 2 days during the week).
Time Frame
Change from baseline to 12 weeks
Title
Colonic Transit Time
Description
Colonic transit time (CTT) as assessed by plain abdominal X-ray following ingestion of oral colonic marker ingestion.
Time Frame
Change from baseline to 12 weeks
Title
Physical Activity
Description
Activity level (GeneActiv 7-10 days).
Time Frame
Change from baseline to 12 weeks
Title
Biochemistry
Description
The Biochemistry department in the Royal Victoria Infirmary in Newcastle upon Tyne will be provided with whole blood. Using this they will measures liver enzymes (alanine transaminase, aspartate aminotransferase, gamma-glutamyl transpeptide), alkaline phosphatase, albumin, bilirubin, lipid profile and C-Peptide tests.
Time Frame
Change from baseline to 12 weeks
Title
Gastrointestinal Health
Description
To determine the impact of a LRD on patient GI symptoms using the Gastrointestinal Quality-of-Life Index. This includes defecation characteristics including laxative use and reported abdominal symptoms categorized as pain or cramps and bloating or flatulence according to five classifications (1, none; 2, mild; 3, moderate; 4, severe; or 5, very severe).
Time Frame
Change from baseline to 12 weeks
Title
Anthropometrics
Description
Weight (kg)
Time Frame
Change from baseline to 12 weeks
Title
Physical Measurements
Description
Body Mass Index
Time Frame
Change from baseline to 12 weeks
Title
Physical Dimensions
Description
Waist to hip ratio (inches)
Time Frame
Change from baseline to 12 weeks
Title
Haematology
Description
The Haematology department in the Royal Victoria Infirmary in Newcastle upon Tyne will be provided with whole blood. Using this they will provide a Full blood count, Haematocrit screen, Ferritin, Vitamin B12, HbA1c and Folate.
Time Frame
Change from baseline to 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, aged 18 and over.
Genetic or biochemical confirmation of mitochondrial disease.
ROME III criteria of constipation (Appendix 2).
Stable gastrointestinal drug regimen prior to commencement of study, at least 3 months prior study inclusion.
No known hypersensitivities to any of the ingredients in the preparations.
Not already implementing a low residue diet.
Competent to make such decisions in the opinion of the investigator.
Females of child bearing age require a negative pregnancy test.
Exclusion Criteria:
Patients with known allergies to any adjuncts in the dietary preparation
Patients with bowel obstruction
Females who are pregnant, lactating or planning a pregnancy.
Planned surgery during the course of the trial.
Participation in another drug trial concurrently or in the preceding 12 weeks.
Any condition which would put the participant at risk if they were to take part in the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Grainne S Gorman, MD
Organizational Affiliation
Newcastle University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Grainne Gorman
City
Newcastle upon Tyne
State/Province
Tyne And Wear
ZIP/Postal Code
NE2 4HH
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Patients will be anonymised, and only raw outcome data will be shared in conjunction with collaborators of the Wellcome Centre for Mitochondrial Research .
Learn more about this trial
Low Residue Diet Study in Mitochondrial Disease
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