Cardiovascular Diseases Clinical Trial
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.
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.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05650307 -
CV Imaging of Metabolic Interventions
|
||
Recruiting |
NCT05654272 -
Development of CIRC Technologies
|
||
Recruiting |
NCT04515303 -
Digital Intervention Participation in DASH
|
||
Completed |
NCT04056208 -
Pistachios Blood Sugar Control, Heart and Gut Health
|
Phase 2 | |
Recruiting |
NCT04417387 -
The Genetics and Vascular Health Check Study (GENVASC) Aims to Help Determine Whether Gathering Genetic Information Can Improve the Prediction of Risk of Coronary Artery Disease (CAD)
|
||
Not yet recruiting |
NCT06211361 -
Cardiac Rehabilitation Program in Patients With Cardiovascular Disease
|
N/A | |
Not yet recruiting |
NCT06032572 -
Evaluation of the Safety and Effectiveness of the VRS100 System in PCI (ESSENCE)
|
N/A | |
Recruiting |
NCT04514445 -
The BRAVE Study- The Identification of Genetic Variants Associated With Bicuspid Aortic Valve Using a Combination of Case-control and Family-based Approaches.
|
||
Enrolling by invitation |
NCT04253054 -
Chinese Multi-provincial Cohort Study-Beijing Project
|
||
Completed |
NCT03273972 -
INvestigating the Lowest Threshold of Vascular bENefits From LDL Lowering With a PCSK9 InhibiTor in healthY Volunteers
|
N/A | |
Completed |
NCT03680638 -
The Effect of Antioxidants on Skin Blood Flow During Local Heating
|
Phase 1 | |
Recruiting |
NCT04843891 -
Evaluation of PET Probe [64]Cu-Macrin in Cardiovascular Disease, Cancer and Sarcoidosis.
|
Phase 1 | |
Completed |
NCT04083846 -
Clinical Study to Investigate the Pharmacokinetic Profiles and Safety of High-dose CKD-385 in Healthy Volunteers(Fed)
|
Phase 1 | |
Completed |
NCT04083872 -
Clinical Study to Investigate the Pharmacokinetic Profiles and Safety of Highdose CKD-385 in Healthy Volunteers(Fasting)
|
Phase 1 | |
Completed |
NCT03619148 -
The Incidence of Respiratory Symptoms Associated With the Use of HFNO
|
N/A | |
Completed |
NCT03693365 -
Fluid Responsiveness Tested by the Effective Pulmonary Blood Flow During a Positive End-expiratory Trial
|
||
Completed |
NCT03466333 -
Postnatal Enalapril to Improve Cardiovascular fUnction Following Preterm Pre-eclampsia
|
Phase 2 | |
Completed |
NCT04082585 -
Total Health Improvement Program Research Project
|
||
Completed |
NCT05132998 -
Impact of a Comprehensive Cardiac Rehabilitation Program Framework Among High Cardiovascular Risk Cancer Survivors
|
N/A | |
Completed |
NCT05067114 -
Solutions for Atrial Fibrillation Edvocacy (SAFE)
|