An interventional study of placebo and Fibre mixture in Health Status, sponsored by Centre for Human Drug Research, Netherlands. Completed at 1 site in Netherlands. Open to participants aged 45 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-08-03.
Sponsored by Centre for Human Drug Research, Netherlands · Not applicable, Interventional, and Health services research
Improving healthy physiological processes through nutritional intervention, as opposed to restoring physiology after disease occurrence, is an important new avenue for the reduction of disease burden in the population. A relatively new target for interventions is the gut microbiome. Dietary fibre is a nutritional intervention shown to alter gut microbiome and function. The present study aims to elucidate the relationship between microbiome modulation with dietary fibre and health. In order to assess health improvement, a meal challenge will be given to characterize the physiological processes and their resilience to challenge in healthy volunteers before and after microbiome modulation.
The gut microbiome has been extensively implicated as an organ involved in various physiological processes such as nutrient and drug metabolism, microbial protection and immunomodulation. The gut microbiome educates the host immune system, promotes homeostasis and protects against systemic inflammation, among other things through production of short-chain fatty acids (SCFAs). An altered microbiome is also involved in inducing low-grade systemic inflammation by translocation of bacterial lipopolysaccharide (LPS) through the intestinal lining. Additionally, the gut microbiome produces trimethylamine (TMA), which when oxidized to trimethylamine N-oxide (TMAO) is documented as an indicator of endothelial dysfunction and cardiovascular health risk. The goal of the present study is to further clarify the relationship between the gut microbiome, homeostasis, immunity and health. This will be achieved by introducing an intervention known to alter gut microbiome characteristics, dietary fibre, and measuring its effect on the gut microbiome on the one hand and the response to metabolic challenge on the other.
Fibre mixtures consisting of indigestible carbohydrates have been shown to alter the composition and function of the gut microbiome. Fibre functions as a substrate for fermentation, creating SCFAs, and as a food source for bacterial commensals regarded as beneficial. Thus, fibre can shift the balance of microbial species in the gut towards beneficial commensals and away from potential pathogens. Moreover, these changes in composition and function of the microbiome can feasibly affect integrity of intestinal lining, TMA production and various other processes, therefore exerting an effect on low-grade inflammation, cardiovascular and metabolic health. The gut microbiome can be analysed using 16s RNA sequencing, quantifying the relative abundance of various bacterial species, and by measuring SCFAs in human plasma, quantifying their production by bacteria in the gut. In this study, we will integrate a third method to measure the gut microbiome. The I-screen, developed by TNO, is a platform in which the in vivo microbiome composition can be mimicked in an in vitro system, allowing for experimental analysis of the effects of compounds and ingredients on the microbiome. With this method, the processes and conditions affecting microbiome composition can be assessed more closely, possibly clarifying specific relationships between intervention and microbiome composition.
The present study aims to assess the effects of this microbiome modulation by evaluating the response to a metabolic challenge, quantified through measurement of a metabolic and inflammatory biomarker panel to create a composite outcome called 'resilience'. This phenotypical flexibility test (PhenFlex, PFT), consisting of a mixed meal with protein, fat and glucose, induces a systemic response which when analysed allows for sensitive assessment of subtle health benefits in otherwise healthy subjects. Results of the PFT are presented as a composite of multiple biomarkers grouped by physiological processes such as inflammation and liver metabolism, creating the 'axes' of a 'health space'. Earlier research shows that selected dietary products affected inflammatory processes, oxidative stress and metabolism, based on dynamic responses after fat load. Other research has shown that the challenge test concept is able to reveal previously unidentified correlations between specific nutrients and health-related processes, and that decreased phenotypic flexibility as measured by PFT can be used to identify people that might benefit from health interventions. Finally, in a human volunteer study with whole grain wheat products researchers were able to show a positive effect on diverse composite markers of resilience, including low grade inflammation, after 12 weeks of exchange of refined wheat for whole grain wheat consumption.
By measuring the effect of our intervention on the gut microbiome with several tools, as well as using the challenge concept for quantifying health, this study is well positioned to provide insight in the specific mechanisms of interaction between microbiome and host, as well as create new evidence-based avenues for the improvement of health.
Centre for Human Drug Research, Netherlands is the lead sponsor of 12 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Abnormal findings in the resting ECG at screening defined as:
Dietary supplement. A mixture of fibres will be administered consisting of 10g of acacia gum powder and 3g of carrot powder. The study product is a fibre mixture consisting of a mix of 10 g of Acacia Gum and 3 g of carrot fibre taken p.o. o.d. in powder form for a total of approximately 10 g of dietary fibre per day.
Dietary Supplement: Fibre mixture
A placebo of the mixture of fibres will be administered.
Other: placebo
Powder consisting of 13 g of digestible carbohydrates with similar appearance as the investigational fibre mixture.
The study product is a fibre mixture consisting of a mix of 10 g of Acacia Gum and 3 g of carrot fibre taken p.o. o.d. in powder form for a total of approximately 10 g of dietary fibre per day.
Microbiome changes
Microbiome changes measured using 16S rRNA sequencing
Time frame: Change from Baseline microbiome changes at week 4
Microbiome changes
Microbiome changes measured using 16S rRNA sequencing
Time frame: Change from Baseline microbiome changes at week 8
Microbiome changes
Microbiome changes measured using 16S rRNA sequencing
Time frame: Change from Baseline microbiome changes at week 12
Microbiome changes
Microbiome changes measured using 16S rRNA sequencing
Time frame: Change from Baseline microbiome changes at week 16
Microbiome changes
Microbiome changes measured using 16S rRNA sequencing
Time frame: Change from Baseline microbiome changes at week 20
Microbiome changes
Microbiome changes measured using 16S rRNA sequencing
Time frame: Change from Baseline microbiome changes at week 24
Microbiome changes
Microbiome changes measured using 16S rRNA sequencing
Time frame: Change from Baseline microbiome changes at week 28
Microbiome changes
Microbiome changes measured using 16S rRNA sequencing
Time frame: Change from Baseline microbiome changes at week 32
Non-esterified fatty acids (NEFAs)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to non-esterified fatty acids (NEFAs)
Time frame: Change from Baseline at week 12
Non-esterified fatty acids (NEFAs)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to non-esterified fatty acids (NEFAs)
Time frame: Change from Baseline at week 20
Non-esterified fatty acids (NEFAs)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to non-esterified fatty acids (NEFAs)
Time frame: Change from Baseline at week 32
Glucose
Response to challenge of metabolic and inflammatory biomarkers including but not limited to glucose
Time frame: Change from Baseline at week 12
Glucose
Response to challenge of metabolic and inflammatory biomarkers including but not limited to glucose
Time frame: Change from Baseline at week 20
Glucose
Response to challenge of metabolic and inflammatory biomarkers including but not limited to glucose
Time frame: Change from Baseline at week 32
Insulin
Response to challenge of metabolic and inflammatory biomarkers including but not limited to insulin
Time frame: Change from Baseline at week 12
Insulin
Response to challenge of metabolic and inflammatory biomarkers including but not limited to insulin
Time frame: Change from Baseline at week 20
Insulin
Response to challenge of metabolic and inflammatory biomarkers including but not limited to insulin
Time frame: Change from Baseline at week 32
Triglycerides (TG)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to triglycerides (TG)
Time frame: Change from Baseline at week 12
Triglycerides (TG)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to triglycerides (TG)
Time frame: Change from Baseline at week 20
Triglycerides (TG)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to triglycerides (TG)
Time frame: Change from Baseline at week 32
High-density lipoprotein (HDL)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to high-density lipoprotein (HDL)
Time frame: Change from Baseline at week 12
High-density lipoprotein (HDL)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to high-density lipoprotein (HDL)
Time frame: Change from Baseline at week 20
High-density lipoprotein (HDL)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to high-density lipoprotein (HDL)
Time frame: Change from Baseline at week 32
Low-density lipoprotein (LDL)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to low-density lipoprotein (LDL)
Time frame: Change from Baseline at week 12
Low-density lipoprotein (LDL)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to low-density lipoprotein (LDL)
Time frame: Change from Baseline at week 20
Low-density lipoprotein (LDL)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to low-density lipoprotein (LDL)
Time frame: Change from Baseline at week 32
Total cholesterol
Response to challenge of metabolic and inflammatory biomarkers including but not limited to total cholesterol.
Time frame: Change from Baseline at week 12
Total cholesterol
Response to challenge of metabolic and inflammatory biomarkers including but not limited to total cholesterol.
Time frame: Change from Baseline at week 20
Total cholesterol
Response to challenge of metabolic and inflammatory biomarkers including but not limited to total cholesterol.
Time frame: Change from Baseline at week 32
Interleukin-6
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-6
Time frame: Change from Baseline at week 32
Interleukin-6
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-6
Time frame: Change from Baseline at week 12
Interleukin-6
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-6
Time frame: Change from Baseline at week 20
Interleukin-8
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-8
Time frame: Change from Baseline at week 12
Interleukin-8
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-8
Time frame: Change from Baseline at week 20
Interleukin-8
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-8
Time frame: Change from Baseline at week 32
Interleukin-10
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-10
Time frame: Change from Baseline at week 12
Interleukin-10
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-10
Time frame: Change from Baseline at week 20
Interleukin-10
Response to challenge of metabolic and inflammatory biomarkers including but not limited to interleukin-10
Time frame: Change from Baseline at week 32
Tumour necrosis factor alpha (TNF-α)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to tumour necrosis factor alpha (TNF-α).
Time frame: Change from Baseline at week 12
Tumour necrosis factor alpha (TNF-α)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to tumour necrosis factor alpha (TNF-α).
Time frame: Change from Baseline at week 20
Tumour necrosis factor alpha (TNF-α)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to tumour necrosis factor alpha (TNF-α).
Time frame: Change from Baseline at week 32
High-sensitivity C-reactive protein (hs-CRP)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to high-sensitivity C-reactive protein (hs-CRP)
Time frame: Change from Baseline at week 12
High-sensitivity C-reactive protein (hs-CRP)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to high-sensitivity C-reactive protein (hs-CRP)
Time frame: Change from Baseline at week 20
High-sensitivity C-reactive protein (hs-CRP)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to high-sensitivity C-reactive protein (hs-CRP)
Time frame: Change from Baseline at week 32
Serum amyloid A (SAA)
Response to challenge of metabolic and inflammatory biomarkers including but not limited serum amyloid A (SAA)
Time frame: Change from Baseline at week 12
Serum amyloid A (SAA)
Response to challenge of metabolic and inflammatory biomarkers including but not limited serum amyloid A (SAA)
Time frame: Change from Baseline at week 20
Serum amyloid A (SAA)
Response to challenge of metabolic and inflammatory biomarkers including but not limited serum amyloid A (SAA)
Time frame: Change from Baseline at week 32
Alanine aminotransferase (ALT)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to alanine aminotransferase (ALT)
Time frame: Change from Baseline at week 12
Alanine aminotransferase (ALT)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to alanine aminotransferase (ALT)
Time frame: Change from Baseline at week 20
Alanine aminotransferase (ALT)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to alanine aminotransferase (ALT)
Time frame: Change from Baseline at week 32
Aspartate aminotransferase (AST)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to aspartate aminotransferase (AST)
Time frame: Change from Baseline at week 12
Aspartate aminotransferase (AST)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to aspartate aminotransferase (AST)
Time frame: Change from Baseline at week 20
Aspartate aminotransferase (AST)
Response to challenge of metabolic and inflammatory biomarkers including but not limited to aspartate aminotransferase (AST)
Time frame: Change from Baseline at week 32
Gamma-glutamyltransferase (GGT).
Response to challenge of metabolic and inflammatory biomarkers including but not limited to gamma-glutamyltransferase (GGT).
Time frame: Change from Baseline at week 12
Gamma-glutamyltransferase (GGT).
Response to challenge of metabolic and inflammatory biomarkers including but not limited to gamma-glutamyltransferase (GGT).
Time frame: Change from Baseline at week 20
Gamma-glutamyltransferase (GGT).
Response to challenge of metabolic and inflammatory biomarkers including but not limited to gamma-glutamyltransferase (GGT).
Time frame: Change from Baseline at week 32
Plan to share: No
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Centre for Human Drug Research, Netherlands