Omega 3 and Fibre Intervention Study to Improve Metabolic Health

July 31, 2018 updated by: Guy's and St Thomas' NHS Foundation Trust

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • London, England, United Kingdom, SE1 7EH
        • King's College London

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Omega 3 fatty acid supplements
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.
Dietary supplement: Omega 3 fatty acid
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.
Active Comparator: Inulin fibre
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.
Dietary supplement: Inulin fibre
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
3-6 weeks
Metabolites
Time Frame: 3-6 months
Measure of faecal metabolites such as short chain fatty acids, blood glucose, blood lipids, ketone bodies
3-6 months
Immune phenotypes
Time Frame: 3-6 months
Markers of immune response measured using peripheral blood mononuclear cells
3-6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assessment of hunger
Time Frame: 6 weeks
Appetite questionnaire
6 weeks
Assessment of sleep
Time Frame: 6 weeks
Sleep pattern will be assessed using a validated questionnaire (Medical Outcomes Survey sleep questionnaire) at baseline, mid-intervention and the end of the intervention.
6 weeks
Assessment of physical exercise
Time Frame: 6 weeks
Physical exercise will be assessed using a validated questionnaire(Sf-12) at baseline, mid-intervention and the end of the intervention.
6 weeks
Assessment of Mood
Time Frame: 6 weeks
Mood will be assessed using a validated questionnaire (HADS, anxiety and depression validated questionnaire) at baseline, mid-intervention and the end of the intervention.
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guy's and St Thomas' NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ana Valdez, Dr, King's College London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 31, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 11, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 20, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 22, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 2, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 31, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 234186

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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