Intestinal DisorderFIBREFECTSNCT03550365
Grain Fibre and Gut Health
A study testing Rye bran bread intervention, Rye bread intervention and Wheat bread diet in people with Intestinal Disorder and Glucose Metabolism Disorders, run by University of Eastern Finland.
Trial summary
Wholegrain fibre is known to affect on the gut health, but also may cause intestinal discomfort. Thus, many individuals may avoid the consumption of whole grain cereals in spite of their known health benefits, and may in this regard consume more restricted diets. Read more about this study
- Who is it for?
- Ages 30 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Intestinal Disorder, Glucose Metabolism Disorders, Inflammation
- What is being tested?
- Rye bran bread intervention, Rye bread intervention and Wheat bread diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2011to 31 Dec 2017
- 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 30 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- BMI 23-30 kg/m2
- abdominally obese (waist circumference >90 cm (men)/ >80 cm (women))
- gastrointestinal symptoms
Who cannot join
- celiac diseases
- extended allergies
- exceptional diets
- IBD patients
- recent (2 mo) use of antibiotic
About this study
Official title: Grain Fibre Modification for Gut-mediated Health Effects
Wholegrain fibre is known to affect on the gut health, but also may cause intestinal discomfort. Thus, many individuals may avoid the consumption of whole grain cereals in spite of their known health benefits, and may in this regard consume more restricted diets. In the preset study the aim was to technologically modify the cereal fibres to improve its usability and to maintain its health beneficial properties. The objective was to investigate intestinal fermentation of grain dietary fibre and associated effects on gut-mediated metabolic health, such as immunological health and adipose tissue function. The hypothesis was that whole grain products maintain their original beneficial health effects and may be better tolerable when the bran is technologically modified. Additionally, it was hypothesized that gut-mediated bioavailability of plant cell wall compounds and their metabolites affect the metabolic health through their immunomodulatory effects.
Read the detailed description
Cereal foods are the most important source of dietary fibre in the Northern European diet. Epidemiological studies have repeatedly shown that diets rich in whole grain foods reduce the risk of type 2 diabetes mellitus and cardiovascular disease. Cereal fibre complex has been suggested as one of the main constituents behind the protective effects. The dietary fibre complex is composed of biopolymers and small molecular weight compounds, that formulate the structure, content and interactions which change during processing. It has been proposed, based on animal data, that the shift in gut microbiota communities is a potential mechanism linking dietary fibre with reduced diabetes risk. Today it is known that gut microbita is actively interacting with dietary fibre producing active functional compounds to the circulation, and thus contribute to health benefits of dietary fibre. The hypothesis that insoluble fibre is a major contributor of the protective effects of whole-grain type cereal foods emphasizes the importance of dietary fibre structure and the conversions of both carbohydrates and polyphenols in the large intestine. The importance of structural features of grain foods in relation to their protective effect against type 2 diabetes was also pointed out in the previous review. On the other hand, soluble arabinoxylo-oligosaccharides have been shown to be selectively fermented by bifidobacteria in in vitro studies, and may thus also be health-protective.
Large intestinal fermentation of the non-digested material causes both hydrolysis of the cell wall matrix and also liberation, further metabolism and absorption of the associated compounds, such as polyphenols. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health, but research into the role of fibre structure and phytochemicals in gut microbiota mediated signalling is in its early phases.The physiological effects of dietary fibre are dependent on the physico-chemical properties, which are mainly influenced by particle size, cell wall architecture, solubility, degree of polymerisation and substitution, distribution of side chains and degree of cross-linking of the polymers. Insoluble dietary fibres are generally more resistant to colonic fermentation than soluble dietary fibre. Solubility of dietary fibre has a major effect also on the bioavailability of fibre associated nutrients and phytochemicals. It has been showed in vitro that enzymatic solubilisation of insoluble dietary fibre stimulated the growth of bifidobacteria and lactobacilli. Additionally, it has been shown that the effect of wheat-bran derived arabinoxylo-oligosaccharides on SCFA production and bifidobacterial numbers in rat faeces depended on the average degree of polymerisation (avDP) of the AXOS preparations - the low avDP preparations increased colonic acetate and butyrate production and boosted the bifidobacteria, whereas the higher avDP preparation suppressed branched SCFA concentrations (a marker for protein fermentation). When, the prebiotic effect of whole-grain wheat and wheat bran breakfast cereals was compared in a human PCT, whole grain cereals proved to be more efficient prebiotics for bifidobacteria whereas ingestion of both products resulted in a significant increase in ferulic acid concentrations in blood.
The objective is to investigate intestinal fermentation of grain dietary fibre and associated effects on gut-mediated metabolic health, such as immunological health and adipose tissue function. Part of the population, however, suffers from discomfort of gastrointestinal tract after consumption of whole grain products, especially rye. The hypothesis is that whole grain products maintain their original beneficial health effects and may be better tolerable when the bran is technologically modified. Moreover, it is hypothesized that gut-mediated bioavailability of plant cell wall compounds and their metabolites affect the metabolic health through their immunomodulatory effects.
- Being tested
- Rye bran bread intervention, Rye bread intervention, Wheat bread diet
- Medical subject headings
- Intestinal Diseases, Glucose Metabolism Disorders, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rye bran bread interventionOther
4 week dietary intervention rich in rye bran bread
Rye bread interventionOther
4 week dietary intervention rich in rye bread
Wheat bread dietOther
4 week dietary intervention rich in wheat bread as an active comparator for previous two interventions
| Study group | Role | What they receive |
|---|---|---|
| Rye bran bread intervention | Experimental | 4 week rye bran bread diet intervention with dietary fibre intake of 30g Receives: Other: Rye bran bread intervention |
| Rye bread intervention | Experimental | 4 week rye bread diet intervention with dietary fibre intake of 30g Receives: Other: Rye bread intervention |
| Wheat bread intervention | Active comparator | 4 week wheat bread diet intervention with dietary fibre intake of 5-20g prior to two other arms Receives: Other: Wheat bread diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
gastrointestinal symptoms
intestinal discomfort measured by questionnaire
Measured: 4 week dietary period
Secondary outcomes (8)
Glucose concentration
fasting plasma glucose concentration (mmol/L)
Measured: 4 week dietary period
Insulin concentration
fasting serum insulin concentration (mU/L)
Measured: 4 week dietary period
fecal microbiota
fecal microbiota composition
Measured: 4 week dietary period
Exhaled air
exhaled air analysis for volatile organic compounds with solid phase (semiquantitative) microextraction and gas chromatography-mass spectrometry
Measured: 4 week dietary period
highly sensitive C-reactive protein
concentration of fasting hs-CRP (mg/L)
Measured: 4 week dietary period
Interleukin 6
Concentration of fasting IL-6 (ug/mL)
Measured: 4 week dietary period
Tumor necrosis factor alfa
concentration of fasting TNF-alfa (pg/mL)
Measured: 4 week dietary period
interleukin 1 receptor antagonist
concentration of fasting IL-1Ra (ng/L)
Measured: 4 week dietary period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2018
- Study start1 Jan 2011
- Primary completion31 Dec 2012
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Intestinal DisorderStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Eastern Finland
- Sponsor type
- University, hospital or other
- Collaborators
- VTT Technical Research Centre of Finland
- Responsible party
- Sponsor
- Investigators
- Marjukka Kolehmainen, Professor, Principal investigator, University of Eastern Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03550365
- Sponsor's protocol ID
- 84/2010
- Acronym
- FIBREFECTS
- Status last verified
- Jun 2018
- First submitted
- 14 May 2018
- Last updated
- 20 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: When data is anonymised it has been planned to be shared. However, in current form, Finnish law does not allow sharing.
Publications
Lappi J, Mykkanen H, Bach Knudsen KE, Kirjavainen P, Katina K, Pihlajamaki J, Poutanen K, Kolehmainen M. Postprandial glucose metabolism and SCFA after consuming wholegrain rye bread and wheat bread enriched with bioprocessed rye bran in individuals with mild gastrointestinal symptoms. Nutr J. 2014 Nov 4;13:104. doi: 10.1186/1475-2891-13-104.
PubMed 25370913Lappi J, Aura AM, Katina K, Nordlund E, Kolehmainen M, Mykkanen H, Poutanen K. Comparison of postprandial phenolic acid excretions and glucose responses after ingestion of breads with bioprocessed or native rye bran. Food Funct. 2013 Jun;4(6):972-81. doi: 10.1039/c3fo60078e. Epub 2013 May 14.
PubMed 23674066Raninen K, Lappi J, Kolehmainen M, Kolehmainen M, Mykkanen H, Poutanen K, Raatikainen O. Diet-derived changes by sourdough-fermented rye bread in exhaled breath aspiration ion mobility spectrometry profiles in individuals with mild gastrointestinal symptoms. Int J Food Sci Nutr. 2017 Dec;68(8):987-996. doi: 10.1080/09637486.2017.1312296. Epub 2017 Apr 9.
PubMed 28391735Keski-Rahkonen P, Kolehmainen M, Lappi J, Micard V, Jokkala J, Rosa-Sibakov N, Pihlajamaki J, Kirjavainen PV, Mykkanen H, Poutanen K, Gunter MJ, Scalbert A, Hanhineva K. Decreased plasma serotonin and other metabolite changes in healthy adults after consumption of wholegrain rye: an untargeted metabolomics study. Am J Clin Nutr. 2019 Jun 1;109(6):1630-1639. doi: 10.1093/ajcn/nqy394.
PubMed 31136658
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Grain Fibre Modification for Gut-mediated Health Effects
- ClinicalTrials.gov ID
- NCT03550365
- Acronym / sponsor ID
- FIBREFECTS / 84/2010
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Eastern FinlandUniversity, hospital or other
- Collaborators
- VTT Technical Research Centre of Finland
- Study start
- 1 Jan 2011 (actual)
- Primary completion
- 31 Dec 2012 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 8 Jun 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.
Wholegrain fibre is known to affect on the gut health, but also may cause intestinal discomfort. Thus, many individuals may avoid the consumption of whole grain cereals in spite of their known health benefits, and may in this regard consume more restricted diets. In the preset study the aim was to technologically modify the cereal fibres to improve its usability and to maintain its health beneficial properties. The objective was to investigate intestinal fermentation of grain dietary fibre and associated effects on gut-mediated metabolic health, such as immunological health and adipose tissue function. The hypothesis was that whole grain products maintain their original beneficial health effects and may be better tolerable when the bran is technologically modified. Additionally, it was hypothesized that gut-mediated bioavailability of plant cell wall compounds and their metabolites affect the metabolic health through their immunomodulatory effects.
Detailed description
Cereal foods are the most important source of dietary fibre in the Northern European diet. Epidemiological studies have repeatedly shown that diets rich in whole grain foods reduce the risk of type 2 diabetes mellitus and cardiovascular disease. Cereal fibre complex has been suggested as one of the main constituents behind the protective effects. The dietary fibre complex is composed of biopolymers and small molecular weight compounds, that formulate the structure, content and interactions which change during processing. It has been proposed, based on animal data, that the shift in gut microbiota communities is a potential mechanism linking dietary fibre with reduced diabetes risk. Today it is known that gut microbita is actively interacting with dietary fibre producing active functional compounds to the circulation, and thus contribute to health benefits of dietary fibre. The hypothesis that insoluble fibre is a major contributor of the protective effects of whole-grain type cereal foods emphasizes the importance of dietary fibre structure and the conversions of both carbohydrates and polyphenols in the large intestine. The importance of structural features of grain foods in relation to their protective effect against type 2 diabetes was also pointed out in the previous review. On the other hand, soluble arabinoxylo-oligosaccharides have been shown to be selectively fermented by bifidobacteria in in vitro studies, and may thus also be health-protective.
Large intestinal fermentation of the non-digested material causes both hydrolysis of the cell wall matrix and also liberation, further metabolism and absorption of the associated compounds, such as polyphenols. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health, but research into the role of fibre structure and phytochemicals in gut microbiota mediated signalling is in its early phases.The physiological effects of dietary fibre are dependent on the physico-chemical properties, which are mainly influenced by particle size, cell wall architecture, solubility, degree of polymerisation and substitution, distribution of side chains and degree of cross-linking of the polymers. Insoluble dietary fibres are generally more resistant to colonic fermentation than soluble dietary fibre. Solubility of dietary fibre has a major effect also on the bioavailability of fibre associated nutrients and phytochemicals. It has been showed in vitro that enzymatic solubilisation of insoluble dietary fibre stimulated the growth of bifidobacteria and lactobacilli. Additionally, it has been shown that the effect of wheat-bran derived arabinoxylo-oligosaccharides on SCFA production and bifidobacterial numbers in rat faeces depended on the average degree of polymerisation (avDP) of the AXOS preparations - the low avDP preparations increased colonic acetate and butyrate production and boosted the bifidobacteria, whereas the higher avDP preparation suppressed branched SCFA concentrations (a marker for protein fermentation). When, the prebiotic effect of whole-grain wheat and wheat bran breakfast cereals was compared in a human PCT, whole grain cereals proved to be more efficient prebiotics for bifidobacteria whereas ingestion of both products resulted in a significant increase in ferulic acid concentrations in blood.
The objective is to investigate intestinal fermentation of grain dietary fibre and associated effects on gut-mediated metabolic health, such as immunological health and adipose tissue function. Part of the population, however, suffers from discomfort of gastrointestinal tract after consumption of whole grain products, especially rye. The hypothesis is that whole grain products maintain their original beneficial health effects and may be better tolerable when the bran is technologically modified. Moreover, it is hypothesized that gut-mediated bioavailability of plant cell wall compounds and their metabolites affect the metabolic health through their immunomodulatory effects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rye bran bread intervention | Experimental | Other: Rye bran bread intervention4 week rye bran bread diet intervention with dietary fibre intake of 30g |
| Rye bread intervention | Experimental | Other: Rye bread intervention4 week rye bread diet intervention with dietary fibre intake of 30g |
| Wheat bread intervention | Active comparator | Other: Wheat bread diet4 week wheat bread diet intervention with dietary fibre intake of 5-20g prior to two other arms |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- BMI 23-30 kg/m2
- abdominally obese (waist circumference >90 cm (men)/ >80 cm (women))
- gastrointestinal symptoms
Key exclusion criteria (5 listed)
- celiac diseases
- extended allergies
- exceptional diets
- IBD patients
- recent (2 mo) use of antibiotic
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 |
|---|---|---|
| Rye bran bread intervention4 week dietary intervention rich in rye bran bread | Other | Rye bran bread intervention |
| Rye bread intervention4 week dietary intervention rich in rye bread | Other | Rye bread intervention |
| Wheat bread diet4 week dietary intervention rich in wheat bread as an active comparator for previous two interventions | Other | Wheat bread intervention |
Primary outcome
gastrointestinal symptoms
Time frame: 4 week dietary period
intestinal discomfort measured by questionnaire
8 secondary outcomes
Glucose concentration
Time frame: 4 week dietary period
Insulin concentration
Time frame: 4 week dietary period
fecal microbiota
Time frame: 4 week dietary period
Exhaled air
Time frame: 4 week dietary period
highly sensitive C-reactive protein
Time frame: 4 week dietary period
Interleukin 6
Time frame: 4 week dietary period
Tumor necrosis factor alfa
Time frame: 4 week dietary period
interleukin 1 receptor antagonist
Time frame: 4 week dietary period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2018.
- Results publication: PubMed 25370913Lappi J, Mykkanen H, Bach Knudsen KE, Kirjavainen P, Katina K, Pihlajamaki J, Poutanen K, Kolehmainen M. Postprandial glucose metabolism and SCFA after consuming wholegrain rye bread and wheat bread enriched with bioprocessed rye bran in individuals with mild gastrointestinal symptoms. Nutr J. 2014 Nov 4;13:104. doi: 10.1186/1475-2891-13-104.
- Results publication: PubMed 23674066Lappi J, Aura AM, Katina K, Nordlund E, Kolehmainen M, Mykkanen H, Poutanen K. Comparison of postprandial phenolic acid excretions and glucose responses after ingestion of breads with bioprocessed or native rye bran. Food Funct. 2013 Jun;4(6):972-81. doi: 10.1039/c3fo60078e. Epub 2013 May 14.
- Results publication: PubMed 28391735Raninen K, Lappi J, Kolehmainen M, Kolehmainen M, Mykkanen H, Poutanen K, Raatikainen O. Diet-derived changes by sourdough-fermented rye bread in exhaled breath aspiration ion mobility spectrometry profiles in individuals with mild gastrointestinal symptoms. Int J Food Sci Nutr. 2017 Dec;68(8):987-996. doi: 10.1080/09637486.2017.1312296. Epub 2017 Apr 9.
- Derived from this study: PubMed 31136658Keski-Rahkonen P, Kolehmainen M, Lappi J, Micard V, Jokkala J, Rosa-Sibakov N, Pihlajamaki J, Kirjavainen PV, Mykkanen H, Poutanen K, Gunter MJ, Scalbert A, Hanhineva K. Decreased plasma serotonin and other metabolite changes in healthy adults after consumption of wholegrain rye: an untargeted metabolomics study. Am J Clin Nutr. 2019 Jun 1;109(6):1630-1639. doi: 10.1093/ajcn/nqy394.
- Individual participant dataSharing planned: Undecided. When data is anonymised it has been planned to be shared. However, in current form, Finnish law does not allow sharing.
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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.
Marjukka Kolehmainen, Professor principal investigator
University of Eastern Finland
Questions about this trial
What is this clinical trial studying?
A study testing Rye bran bread intervention, Rye bread intervention and Wheat bread diet in people with Intestinal Disorder and Glucose Metabolism Disorders, run by University of Eastern Finland.
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 3 inclusion and 5 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: finished, as of the sponsor's last update on 20 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
gastrointestinal symptoms (time frame: 4 week dietary period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03550365, which also lists 4 linked publications.
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 20 Jun 2018.