Metabolic DiseaseNCT03442348
Omega 3 and Fibre Intervention Study to Improve Metabolic Health
A study testing Omega 3 fatty acid and Inulin fibre in people with Metabolic Disease and Immune Function, run by Guy's and St Thomas' NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Metabolic syndrome represents a major health burden worldwide affecting 20-30% of the population. This clustering of abnormalities that confers an increased risk of cardiovascular disease and type 2 diabetes mellitus, is the hallmark of "unhealthy" aging in longevity studies. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolic Disease, Immune Function, Cardiovascular Diseases
- What is being tested?
- Omega 3 fatty acid and Inulin fibre
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 May 2018to 28 Feb 2020
- Phase
- Interventional
- 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 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participant eligibility includes those aged >18 years who have a body mass index (BMI) between 20 and 39.9 kg/m2. Participants must have low habitual fibre consumption of less than 15g/day.
Who cannot join
- Refuse or are unable to give informed consent to participate in the study
- Consume on average >15 g/day of NSP and RS (men and women) as part of their diets
- Are taking the following medications: immunosuppressants, amiodarone and/or perhexiline
- Are currently following or anticipated to commence a specialised commercially available weight loss diet and/or program
- Have a diagnosis of insulin dependent diabetes mellitus
- Have a current or prior history of cardiovascular, cerebrovascular or peripheral vascular disease
Show all 13Show fewer
- Have clinically relevant pulmonary, gastro-intestinal, renal, metabolic, hematological, neurological, psychiatric, systemic or any acute infectious disease or signs of acute illness
- Are women who are pregnant
- Have psychosocial or gastrointestinal (e.g. malabsorptive conditions such as IBS, coeliac)
- Have contraindications included bulimia nervosa, substance abuse, clinically significant depression, or current psychiatric care
- Have had a recent (within 3 months) of change in dose/regime or introduction of vitamin E, C or high dose vitamin D (>3000 IU), fish oil, prebiotics or probiotics.
- Are vegetarian and thus unwilling to take fish oil capsules
- People on anticoagulants and people with atrial fibrillation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Utilising Omega 3 and Fibre to Improve Metabolic Health: A Proof of Concept Nutritional Intervention Study Targeting the Gut Microbiome
Metabolic syndrome represents a major health burden worldwide affecting 20-30% of the population. This clustering of abnormalities that confers an increased risk of cardiovascular disease and type 2 diabetes mellitus, is the hallmark of "unhealthy" aging in longevity studies. Preventive strategies have so far failed since they have focused mainly on reducing caloric intake, ignoring the metabolic dysfunction in the aging body. The growing importance of the gut microbiota in all aspects of human health is clear, and unlike our genomes is potentially highly modifiable and tightly related to metabolic and immune efficiency, energy and fatty acid metabolism and satiety hormones. The investigators and others have reported that higher microbiome diversity correlates with significantly lower long-term risk of weight gain and metabolic syndrome. The investigators have recently shown that serum levels of omega-3 fatty acids correlate with higher microbiome diversity, and increased abundance of bacteria that produce butyrate are linked to lower inflammation of the gut. The investigators therefore propose to carry out a proof of concept nutritional intervention study in the TwinsUK cohort. The TwinsUK sample is probably the most detailed omic and phenotypic resource in the world and is ideal for this study. The mechanisms that result in improved microbiome composition and diversity will be explored in a highly focused novel interventional study hypothesizing that key fatty acid pathways are crucially involved in the link between diet, microbiome, immune phenotypes and metabolic syndrome. The specific objectives are to measure changes in gut microbiome composition in response to fibre supplementation compared to omega-3 fatty acid supplementation. The study will measure faecal metabolites relevant to fatty acid metabolism (short chain fatty acids), the abundance of microbial species linked to higher or lower inflammation and immune cell phenotypes to unravel the link between inflammation, diet and metabolic syndrome. There is a real lack of good diet intervention studies in this field and if successful this trial will pave the way to funding a wide variety of other diet intervention studies.
Read the detailed description
Diet and nutrition are key determinants of chronic disease. However, additional information is needed on which bioactive compounds and in what amounts they should be consumed to obtain a given health benefit. One of the biggest recent breakthroughs in science has been realisation of the importance of the contents, function and homeostasis of the gut microbiome in human health.
Dietary fibre: The influence of diet on the microbiome is illustrated by vast differences across cultures where African communities who have a plant based diet consume 7-fold more fibre compared with the West obtaining more of their energy requirements via utilization of gut microbiota. Hunter-gatherers have been shown to have 30-40% greater numbers and diversity of species than Western populations. Also, a multigenerational murine study showed a Western diet was responsible for depletion of microbiota diversity. Diversity is emerging as the common marker of good gut health across populations and related to production of beneficial short chain fatty acids (SCFAs). The fermentation of dietary fibre changes the profile of microbial-derived metabolites within the GI tract, most importantly SCFAs. Low fibre intake results in reduced production of SCFAs and also shifts the gastrointestinal (GI) microbiota metabolism to the utilization of less favourable nutrients, leading to the production of potentially detrimental metabolites derived from the fermentation of amino acids. Prevention of the generation of such metabolites through dietary fibre is one of the main mechanisms for the prevention of colon cancer. There is considerable observational evidence that fibre intake is beneficial for human health from observational epidemiological studies. However, findings from intervention studies are less consistent. The variability in human intervention studies could also arise from the highly inter-individualized responses of the human GI microbiome to dietary fibres providing a rationale for the individualization of dietary fibre applications.
Omega 3 fatty acids: In humans, omega-3 fatty acids are readily incorporated into cell membranes resulting in increased cell fluidity, which may improve glucose transport. Additionally, omega-3 supplementation enhances resting fat oxidation and glycogen storage, potentially contributing to improved insulin sensitivity. Omega-3 supplementation may also reduce cardiovascular disease risk by reducing circulating very-low-density lipoproteins (LDL), triacylglycerols and free fatty acids (FFA). It also has additional anti-inflammatory and antithrombotic properties. Previously published data by the investigators suggest the potential use of omega-3 supplementation to improve the microbiome composition. Although trials of supplements are inconsistent, current recommended daily intake for omega-3 is 250 mg (active EPA and DHA) for the general population and higher for patients with cardiovascular disease.
The study will be a proof of concept mechanistic study that will show to what extent omega-3 fatty acid supplementation adds to the benefits of a probiotic intervention in terms both of microbiome diversity and composition and of SCFA production. Moreover, it will show whether this results in measurable improvements in other markers of fatty acid metabolism and in the balance of various T-cell lineages some of which are pro-inflammatory and others which are anti-inflammatory. In this study we will test if 1) intake of fibre induces an increase in microbiome diversity, increased SCFA production in the gut and less inflammatory T-cell composition 2) omega-3 supplementation provides a comparable benefit in terms of microbiome diversity and cardiometabolic improvement to that supplied by fibre.
The study will be a randomised controlled intervention study in which participants will be grouped into two different treatment arms. Randomisation will control for equal distribution of key characteristics that may confound between group comparisons and will be assessed by analysis of baseline data.
80 participants over the age of 18 years will be recruited from the TwinsUK database.The total length of the dietary intervention will be 6 weeks with an initial visit at baseline, and one final visit at 6 weeks.
- Being tested
- Omega 3 fatty acid, Inulin fibre
- Keywords
- Omega 3, Fibre, Gut microbiome, Metabolic profile, Dietary intervention, Randomised Control Trial
- Medical subject headings
- Metabolic Diseases, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omega 3 fatty acidDietary supplement
Participants in the bottom median of dietary fibre intake (<15 g per day) will be randomised into one of two arms. Participants in the second arm (N>32) will be required to take one 500mg capsule of Omega 3 along with a meal daily for 6 weeks.
Inulin fibreDietary supplement
The participants in the control arm (N>32) will be asked to take 20 g of fibre (resistant starch + inulin) per day that are known favour production of SCFAs in the colon for a period of 6 weeks. The inulin powder will be provided in pre-weighed sachets containing 10g each which can be taken mixed in water or a suitable beverage of choice taken twice (morning and evening) per day.
| Study group | Role | What they receive |
|---|---|---|
| Omega 3 fatty acid supplements | Experimental | Participants in this arm (N>32) will be required to take one 500mg capsule of Omega 3 along with a meal daily for 6 weeks. Receives: Dietary Supplement: Omega 3 fatty acid |
| Inulin fibre | Active comparator | The participants in the control arm (N>32) will be asked to take 20 g of fibre (inulin fibre) per day for a period of 6 weeks. Receives: Dietary Supplement: Inulin fibre |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gut microbiome diversity
16s sequencing will be carried out on whole stool samples to measure gut microbial diversity and composition. Stool samples collected and frozen within two hours will be assessed in greater detail for markers of microbiome function and gut health which include measuring key short-chain fatty acids using mass spectrometry.
Measured: 3-6 weeks
Metabolites
Measure of faecal metabolites such as short chain fatty acids, blood glucose, blood lipids, ketone bodies
Measured: 3-6 months
Immune phenotypes
Markers of immune response measured using peripheral blood mononuclear cells
Measured: 3-6 months
Secondary outcomes (4)
Assessment of hunger
Appetite questionnaire
Measured: 6 weeks
Assessment of sleep
Sleep pattern will be assessed using a validated questionnaire (Medical Outcomes Survey sleep questionnaire) at baseline, mid-intervention and the end of the intervention.
Measured: 6 weeks
Assessment of physical exercise
Physical exercise will be assessed using a validated questionnaire(Sf-12) at baseline, mid-intervention and the end of the intervention.
Measured: 6 weeks
Assessment of Mood
Mood will be assessed using a validated questionnaire (HADS, anxiety and depression validated questionnaire) at baseline, mid-intervention and the end of the intervention.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start31 May 2018
- Primary completion28 Feb 2019 (estimated)
- Study completion28 Feb 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic DiseaseStudies of the same condition, open and under way.
- More trials run by Guy's and St Thomas' NHS Foundation TrustThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study will be a randomised controlled parallel intervention study in which participants will be grouped into 2 different study arms.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ana Valdez, Dr, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03442348
- Sponsor's protocol ID
- 234186
- Status last verified
- Jul 2018
- First submitted
- 11 Oct 2017
- Last updated
- 2 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Utilising Omega 3 and Fibre to Improve Metabolic Health: A Proof of Concept Nutritional Intervention Study Targeting the Gut Microbiome
- ClinicalTrials.gov ID
- NCT03442348
- Acronym / sponsor ID
- 234186
- Keywords
- Omega 3, Fibre, Gut microbiome, Metabolic profile, Dietary intervention, Randomised Control Trial
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Guy's and St Thomas' NHS Foundation TrustUniversity, hospital or other
- Study start
- 31 May 2018 (actual)
- Primary completion
- 28 Feb 2019 (estimated)
- Study completion
- 28 Feb 2020 (estimated)
- First posted
- 22 Feb 2018 (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.
Metabolic syndrome represents a major health burden worldwide affecting 20-30% of the population. This clustering of abnormalities that confers an increased risk of cardiovascular disease and type 2 diabetes mellitus, is the hallmark of "unhealthy" aging in longevity studies. Preventive strategies have so far failed since they have focused mainly on reducing caloric intake, ignoring the metabolic dysfunction in the aging body. The growing importance of the gut microbiota in all aspects of human health is clear, and unlike our genomes is potentially highly modifiable and tightly related to metabolic and immune efficiency, energy and fatty acid metabolism and satiety hormones. The investigators and others have reported that higher microbiome diversity correlates with significantly lower long-term risk of weight gain and metabolic syndrome. The investigators have recently shown that serum levels of omega-3 fatty acids correlate with higher microbiome diversity, and increased abundance of bacteria that produce butyrate are linked to lower inflammation of the gut. The investigators therefore propose to carry out a proof of concept nutritional intervention study in the TwinsUK cohort. The TwinsUK sample is probably the most detailed omic and phenotypic resource in the world and is ideal for this study. The mechanisms that result in improved microbiome composition and diversity will be explored in a highly focused novel interventional study hypothesizing that key fatty acid pathways are crucially involved in the link between diet, microbiome, immune phenotypes and metabolic syndrome. The specific objectives are to measure changes in gut microbiome composition in response to fibre supplementation compared to omega-3 fatty acid supplementation. The study will measure faecal metabolites relevant to fatty acid metabolism (short chain fatty acids), the abundance of microbial species linked to higher or lower inflammation and immune cell phenotypes to unravel the link between inflammation, diet and metabolic syndrome. There is a real lack of good diet intervention studies in this field and if successful this trial will pave the way to funding a wide variety of other diet intervention studies.
Detailed description
Diet and nutrition are key determinants of chronic disease. However, additional information is needed on which bioactive compounds and in what amounts they should be consumed to obtain a given health benefit. One of the biggest recent breakthroughs in science has been realisation of the importance of the contents, function and homeostasis of the gut microbiome in human health.
Dietary fibre: The influence of diet on the microbiome is illustrated by vast differences across cultures where African communities who have a plant based diet consume 7-fold more fibre compared with the West obtaining more of their energy requirements via utilization of gut microbiota. Hunter-gatherers have been shown to have 30-40% greater numbers and diversity of species than Western populations. Also, a multigenerational murine study showed a Western diet was responsible for depletion of microbiota diversity. Diversity is emerging as the common marker of good gut health across populations and related to production of beneficial short chain fatty acids (SCFAs). The fermentation of dietary fibre changes the profile of microbial-derived metabolites within the GI tract, most importantly SCFAs. Low fibre intake results in reduced production of SCFAs and also shifts the gastrointestinal (GI) microbiota metabolism to the utilization of less favourable nutrients, leading to the production of potentially detrimental metabolites derived from the fermentation of amino acids. Prevention of the generation of such metabolites through dietary fibre is one of the main mechanisms for the prevention of colon cancer. There is considerable observational evidence that fibre intake is beneficial for human health from observational epidemiological studies. However, findings from intervention studies are less consistent. The variability in human intervention studies could also arise from the highly inter-individualized responses of the human GI microbiome to dietary fibres providing a rationale for the individualization of dietary fibre applications.
Omega 3 fatty acids: In humans, omega-3 fatty acids are readily incorporated into cell membranes resulting in increased cell fluidity, which may improve glucose transport. Additionally, omega-3 supplementation enhances resting fat oxidation and glycogen storage, potentially contributing to improved insulin sensitivity. Omega-3 supplementation may also reduce cardiovascular disease risk by reducing circulating very-low-density lipoproteins (LDL), triacylglycerols and free fatty acids (FFA). It also has additional anti-inflammatory and antithrombotic properties. Previously published data by the investigators suggest the potential use of omega-3 supplementation to improve the microbiome composition. Although trials of supplements are inconsistent, current recommended daily intake for omega-3 is 250 mg (active EPA and DHA) for the general population and higher for patients with cardiovascular disease.
The study will be a proof of concept mechanistic study that will show to what extent omega-3 fatty acid supplementation adds to the benefits of a probiotic intervention in terms both of microbiome diversity and composition and of SCFA production. Moreover, it will show whether this results in measurable improvements in other markers of fatty acid metabolism and in the balance of various T-cell lineages some of which are pro-inflammatory and others which are anti-inflammatory. In this study we will test if 1) intake of fibre induces an increase in microbiome diversity, increased SCFA production in the gut and less inflammatory T-cell composition 2) omega-3 supplementation provides a comparable benefit in terms of microbiome diversity and cardiometabolic improvement to that supplied by fibre.
The study will be a randomised controlled intervention study in which participants will be grouped into two different treatment arms. Randomisation will control for equal distribution of key characteristics that may confound between group comparisons and will be assessed by analysis of baseline data.
80 participants over the age of 18 years will be recruited from the TwinsUK database.The total length of the dietary intervention will be 6 weeks with an initial visit at baseline, and one final visit at 6 weeks.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- The study will be a randomised controlled parallel intervention study in which participants will be grouped into 2 different study arms.
| Arm | Type | Receives |
|---|---|---|
| Omega 3 fatty acid supplements | Experimental | Dietary Supplement: Omega 3 fatty acidParticipants in this arm (N>32) will be required to take one 500mg capsule of Omega 3 along with a meal daily for 6 weeks. |
| Inulin fibre | Active comparator | Dietary Supplement: Inulin fibreThe participants in the control arm (N>32) will be asked to take 20 g of fibre (inulin fibre) per day for a period of 6 weeks. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Participant eligibility includes those aged >18 years who have a body mass index (BMI) between 20 and 39.9 kg/m2. Participants must have low habitual fibre consumption of less than 15g/day.
Key exclusion criteria (13 listed)
- Refuse or are unable to give informed consent to participate in the study
- Consume on average >15 g/day of NSP and RS (men and women) as part of their diets
- Are taking the following medications: immunosuppressants, amiodarone and/or perhexiline
- Are currently following or anticipated to commence a specialised commercially available weight loss diet and/or program
- Have a diagnosis of insulin dependent diabetes mellitus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omega 3 fatty acidParticipants in the bottom median of dietary fibre intake (<15 g per day) will be randomised into one of two arms. Participants in the second arm (N>32) will be required to take one 500mg capsule of Omega 3 along with a meal daily for 6 weeks. | Dietary supplement | Omega 3 fatty acid supplements |
| Inulin fibreThe participants in the control arm (N>32) will be asked to take 20 g of fibre (resistant starch + inulin) per day that are known favour production of SCFAs in the colon for a period of 6 weeks. The inulin powder will be provided in pre-weighed sachets containing 10g each which can be taken mixed in water or a suitable beverage of choice taken twice (morning and evening) per day. | Dietary supplement | Inulin fibre |
Primary outcome
Gut microbiome diversity
Time frame: 3-6 weeks
16s sequencing will be carried out on whole stool samples to measure gut microbial diversity and composition. Stool samples collected and frozen within two hours will be assessed in greater detail for markers of microbiome function and gut health which include measuring key short-chain fatty acids using mass spectrometry.
Metabolites
Time frame: 3-6 months
Measure of faecal metabolites such as short chain fatty acids, blood glucose, blood lipids, ketone bodies
Immune phenotypes
Time frame: 3-6 months
Markers of immune response measured using peripheral blood mononuclear cells
4 secondary outcomes
Assessment of hunger
Time frame: 6 weeks
Assessment of sleep
Time frame: 6 weeks
Assessment of physical exercise
Time frame: 6 weeks
Assessment of Mood
Time frame: 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2018.
- Individual participant dataSharing planned: Undecided
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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.
Ana Valdez, Dr principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Omega 3 fatty acid and Inulin fibre in people with Metabolic Disease and Immune Function, run by Guy's and St Thomas' NHS Foundation Trust 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 1 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 2 Aug 2018. 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?
Results are not available in the source record.
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?
Gut microbiome diversity (time frame: 3-6 weeks). The study lists 3 primary outcomes in all. 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 2 Aug 2018.