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CompletedNCT03388528LRDUpdated Oct 11, 2019

Low Residue Diet Study in Mitochondrial Disease

An interventional study of Low Residue Diet Intervention in Mitochondrial Diseases, sponsored by Newcastle University. Completed at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-11.

Sponsored by Newcastle University · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
36
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Mitochondrial Diseases

Keywords

  • Dysmotility
  • Microbiome
  • Transit Time
  • Gastrointestinal
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    Treatment Group

    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.

    Dietary Supplement: Low Residue Diet Intervention

Interventions

  • Dietary supplementLow Residue Diet Intervention

    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.

05

What researchers measure

Primary outcomes

  1. Assess tolerability of a Low Residue Diet (LRD) in mitochondrial patients

    Tolerability of the LRD will be assessed using food diaries

    Time frame: Change from baseline to 12 weeks

  2. 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

    Time frame: Change from baseline to 12 weeks

Secondary outcomes

  1. Gastrointestinal Dysmotility

    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

  2. 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.

    Time frame: Change from baseline to 12 weeks

  3. Gut Microbiome changes

    Assess effect of a LRD on gut metagenomics

    Time frame: Change from baseline to 12 weeks

  4. 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.

    Time frame: Baseline only (prior to any intervention)

  5. 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).

    Time frame: Change from baseline to 12 weeks

  6. Colonic Transit Time

    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

  7. Physical Activity

    Activity level (GeneActiv 7-10 days).

    Time frame: Change from baseline to 12 weeks

  8. 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.

    Time frame: Change from baseline to 12 weeks

  9. 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).

    Time frame: Change from baseline to 12 weeks

  10. Anthropometrics

    Weight (kg)

    Time frame: Change from baseline to 12 weeks

  11. Physical Measurements

    Body Mass Index

    Time frame: Change from baseline to 12 weeks

  12. Physical Dimensions

    Waist to hip ratio (inches)

    Time frame: Change from baseline to 12 weeks

  13. 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.

    Time frame: Change from baseline to 12 weeks

06

Study locations

1 site
  • Grainne Gorman
    Newcastle upon Tyne, Tyne And Wear NE2 4HH, United Kingdom
07

References and documents

Individual participant data

Plan to share: No — Patients will be anonymised, and only raw outcome data will be shared in conjunction with collaborators of the Wellcome Centre for Mitochondrial Research .

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03388528
Lead sponsor
Newcastle University
Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
Responsible party
Sponsor
First posted
Jan 3, 2018
Start date
Sep 8, 2017
Primary completion
Feb 7, 2019
Completion
Feb 7, 2019
Last update
Oct 11, 2019

Study contacts

Grainne S Gorman, MD
principal investigator · Newcastle University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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