Back to resultsEffects of Changing Intestinal Transit Time on Gut Microbial Composition and Metabolism (PRIMA-KOST)
Primary Purpose
Diet, Healthy, Metabolic Disease
Status
Not yet recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Diet + laxative
Diet only
Sponsored by
About this trial
This is an interventional basic science trial for Diet, Healthy focused on measuring Microbiome, Metabolomics, Transit time, Nutrition, Dietary fibre
Eligibility Criteria
Inclusion Criteria: 18.5-30.0 kg/m2 BMI Self-reported ≤3.5 spontaneous bowel movements per week Willing to collect urine and stool samples at home and able to temporarily store them in their own freezer in a provided container. Willing to eat the foods provided. Owns a smartphone (iOS 11.0 and later or Android 5.0 and up) with access to the internet. Exclusion Criteria: Pregnant or lactating women. Diagnosis of irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), inflammatory bowel diseases (IBD), Gastrointestinal obstruction, or Ischemic colitis Diagnosed constipation according to the ROME IV criteria Intake of antibiotics ˂ 1month, or any medication that can affect the outcomes of the study Regular use of diarrhea inhibitors or laxatives Dysphagia Any chronic disease that can affect the outcomes of the study or pose a risk when consuming Movicol Intake of medications potentially altering gastric pH (proton pump inhibitors, histamine receptor antagonists, antacids) Intake of medications potentially altering the gastrointestinal motility (prokinetics, antiemetic agents, anti-cholinergic agents, narcotic analgetics, nonsteroidal anti-inflammatory drugs, and peroral glucocorticoids) Concurrent participation in another trial Any condition that makes the project responsible researcher to doubt the feasibility of the volunteer´s participation
Sites / Locations
- University of Copenhagen, Department of Nutrition, Exercise and Sports
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
High-fiber diet
Low-fiber diet
Arm Description
The high-fiber diet will consist of foods rich in dietary fiber such as coarse vegetables, wholegrain bread, and fruits representing a broad range of dietary fibers aiming for ≈40 g of fiber/10 MJ.
The low-fiber diet will consist of foods poor in fiber such as white bread and refined foods aiming for ≈10 g of fiber/10 MJ.
Outcomes
Primary Outcome Measures
Fecal butyrate over urine p-cresol sulfate ratio
Changes in ratio between fecal butyrate (reflecting saccharolytic fermentation) and urine p-cresol sulfate (reflecting proteolytic fermentation) between interventions.
Secondary Outcome Measures
Whole gut transit time measured by sweet corn
Changes in whole gut transit time between interventions determined by the passage time of sweet corn.
Whole gut transit time measured by blue muffins
Changes in whole gut transit time between interventions determined by the passage time of muffins with blue dye.
Stool consistency
Changes in stool consistency determined by Bristol Stool Scale. The Bristol Stool Scale measures stool consistency on a scale from 1-7 with high numbers reflecting loose stool.
Change in bowel movement frequency
Changes in bowel movement frequency will be measured by the participants recording every bowel movement in a defecation diary during the study.
Fecal water content in percentage of stool weight
Change in fecal water content between interventions.
Fecal concentration of short-chain fatty acids
Change in concentration of short-chain fatty acids between interventions.
Fecal pH
Change in fecal pH level between interventions.
Fecal ammonia concentration
Change in ammonia content between interventions.
Concentration of fasting plasma short-chain fatty acids
Change in concentration of short-chain fatty acids between interventions.
Fasting plasma concentrations of bile acids
Change in concentration of bile acids in fasting blood between interventions.
Fasting breath methane and hydrogen levels in parts per million
Changes in fasting breath methane and hydrogen concentration measured in parts per million (PPM) in exhalations between interventions.
Microbial metabolites in urine from proteolytic fermentation as assessed by mass spectrometry
Changes in the urine concentration of metabolites of microbial proteolysis between interventions.
Microbial metabolites in blood from proteolytic fermentation as assessed by mass spectrometry
Changes in the blood concentration of metabolites of microbial proteolysis between interventions.
Fecal metabolome as assessed by untargeted metabolomics
Changes in the fecal metabolome between interventions.
Gut microbiome assessed by shotgun sequencing
Changes in gut microbiota composition between interventions.
Gut microbiome assessed by 16S amplicon sequencing
Changes in gut microbiota composition between interventions.
Full Information
NCT ID
NCT06022302
First Posted
August 11, 2023
Last Updated
September 6, 2023
Sponsor
University of Copenhagen
Collaborators
Technical University of Denmark, KU Leuven, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT06022302
Brief Title
Effects of Changing Intestinal Transit Time on Gut Microbial Composition and Metabolism
Acronym
PRIMA-KOST
Official Title
Effects of Changing Intestinal Transit Time on Gut Microbial Composition and Metabolism During a Dietary Intervention With Low and High Fiber.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
January 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Copenhagen
Collaborators
Technical University of Denmark, KU Leuven, University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this study is to investigate how a short versus a long transit time impacts the gut microbiome's response to a high-fiber and a low-fiber diet, respectively. Such insights could help us understand personal responses to diets and be a first step towards personalized dietary recommendations targeting the gut microbiome.
Detailed Description
The study consists of two parallel arms of whole-meal diets, a low-fiber diet, and a high-fiber diet, respectively. Each arm is designed as a cross-over where participants, in random order, are administered a laxative (Movicol) along with the provided diet to shorten their intestinal transit time or simply consume the provided whole-meal diet (control).
The two intervention periods both involve the following:
One week of run-in where participants consume the provided whole-meal diet.
One week where participants either consume Movicol with the provided whole-meal diet or simply continue consuming the provided whole-meal diet (control).
Both arms begin with a screening visit and one week where participants consume and record their habitual diets. Subsequently, the first intervention period follows with one visit before and after each of the two weeks (visit 1-3) followed by the second intervention period with one visit before and after each of the two weeks (visit 4-6). The two cross-over periods are split by a washout of at least two weeks.
The study thus runs for approximately 7-8 weeks depending on the length of the washout and consists of seven visits (one screening visit and six regular visits) in total.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diet, Healthy, Metabolic Disease
Keywords
Microbiome, Metabolomics, Transit time, Nutrition, Dietary fibre
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Overall, there are two parallel arms (low- and high-fiber diet) to which the participants will be randomized with an allocation ratio 1:1. In each arm participants will be exposed to a crossover design where participants in random order will continue on the meal intervention alone (control) or receive Movicol (a laxative) along with the meal intervention to shorten intestinal transit time.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
High-fiber diet
Arm Type
Experimental
Arm Description
The high-fiber diet will consist of foods rich in dietary fiber such as coarse vegetables, wholegrain bread, and fruits representing a broad range of dietary fibers aiming for ≈40 g of fiber/10 MJ.
Arm Title
Low-fiber diet
Arm Type
Experimental
Arm Description
The low-fiber diet will consist of foods poor in fiber such as white bread and refined foods aiming for ≈10 g of fiber/10 MJ.
Intervention Type
Drug
Intervention Name(s)
Diet + laxative
Intervention Description
The participants will start by consuming one sacket of Movicol powder (13 g macrogol 3350) on the first day. On day 2, the participants will consume two sackets of Movicol powder (26 g macrogol 3350), one with breakfast in the morning and one before sleep in the evening. The participants will continue consuming two sackets per day (one morning, one evening) until the following study visit, day 8 (seven days in total). If the participants have a very loose stomach (recorded as Bristol stool scale ≥6), they will be instructed to reduce Movicol by one sacket/day. In case the participants have not passed a stool on day 2 or in the morning of day 3, the participants will increase the dose to a maximum of three sackets of Movicol powder (39 g macrogol 3350) per day (morning, noon, and evening) and continue this until the following study visit at day 8. If three sackets cause very loose stomach the participants will decrease the number of sackets consumed.
Intervention Type
Other
Intervention Name(s)
Diet only
Other Intervention Name(s)
Control
Intervention Description
This is only a control and participants will not receive Movicol.
Primary Outcome Measure Information:
Title
Fecal butyrate over urine p-cresol sulfate ratio
Description
Changes in ratio between fecal butyrate (reflecting saccharolytic fermentation) and urine p-cresol sulfate (reflecting proteolytic fermentation) between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Secondary Outcome Measure Information:
Title
Whole gut transit time measured by sweet corn
Description
Changes in whole gut transit time between interventions determined by the passage time of sweet corn.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Whole gut transit time measured by blue muffins
Description
Changes in whole gut transit time between interventions determined by the passage time of muffins with blue dye.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Stool consistency
Description
Changes in stool consistency determined by Bristol Stool Scale. The Bristol Stool Scale measures stool consistency on a scale from 1-7 with high numbers reflecting loose stool.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Change in bowel movement frequency
Description
Changes in bowel movement frequency will be measured by the participants recording every bowel movement in a defecation diary during the study.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal water content in percentage of stool weight
Description
Change in fecal water content between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal concentration of short-chain fatty acids
Description
Change in concentration of short-chain fatty acids between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal pH
Description
Change in fecal pH level between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal ammonia concentration
Description
Change in ammonia content between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Concentration of fasting plasma short-chain fatty acids
Description
Change in concentration of short-chain fatty acids between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fasting plasma concentrations of bile acids
Description
Change in concentration of bile acids in fasting blood between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fasting breath methane and hydrogen levels in parts per million
Description
Changes in fasting breath methane and hydrogen concentration measured in parts per million (PPM) in exhalations between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Microbial metabolites in urine from proteolytic fermentation as assessed by mass spectrometry
Description
Changes in the urine concentration of metabolites of microbial proteolysis between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Microbial metabolites in blood from proteolytic fermentation as assessed by mass spectrometry
Description
Changes in the blood concentration of metabolites of microbial proteolysis between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal metabolome as assessed by untargeted metabolomics
Description
Changes in the fecal metabolome between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Gut microbiome assessed by shotgun sequencing
Description
Changes in gut microbiota composition between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Gut microbiome assessed by 16S amplicon sequencing
Description
Changes in gut microbiota composition between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Other Pre-specified Outcome Measures:
Title
Urine metabolome as assessed by untargeted metabolomics
Description
Changes in the urine metabolome between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Blood metabolome as assessed by untargeted metabolomics
Description
Changes in the blood metabolome between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal microbial metabolites of proteolytic fermentation measured by mass spectrometry
Description
Assessment of changes in fecal microbial metabolites of proteolytic fermentation (amino acid-derived metabolites).
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal enzymatic activities
Description
Assessment of changes in enzymatic activities measured in fecal samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal residual carbohydrate concentration
Description
Change in residual carbohydrate concentration measured in fecal samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal energy density
Description
Change in fecal energy density measured by bomb calorimetry in fecal samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal redox potential measured in mV
Description
Change in redox potential measured in fecal samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal carbon:nitrogen (C:N) ratio
Description
Change in C:N ratio measured in fecal samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal microbial load (cells per gram)
Description
Change in microbial load in fecal samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Fecal calprotectin concentration
Description
Change in concentration of calprotectin measured in fecal samples between interventions. Used as a measure of intestinal inflammation.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Change in various markers related to glucose metabolism
Description
Changes in the concentration of various standard markers of glucose metabolism in fasting blood samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Change in various markers related to lipid metabolism
Description
Changes in concentration of various standard biochemical markers of lipid metabolism in fasting blood samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Change in various markers of inflammation
Description
Change in concentration of various inflammatory markers in fasting blood between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Change in various appetite hormones
Description
Change in concentration of various appetite hormones in fasting blood between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Urinary creatinine concentration
Description
Measurement of urinary levels of creatinine from spot urine samples between interventions.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Amylase gene copy number
Description
Measurement of amylase gene copy numbers from blood samples at visit 1 to determine the phenotype of the participants.
Time Frame
At visit 1
Title
Change in body weight
Description
Change in body weight is measured using a calibrated digital scale to ensure/monitor weight stability throughout the study.
Time Frame
From baseline through to study completion, an average of 8 weeks
Title
Measurement of breath hydrogen and methane profiles in parts per million (Area under the curve)
Description
Measurement of the hydrogen and methane concentrations, in parts per million (PPM), in morning, noon, and evening breath exhalations every day during the study using a portable breath analyzer.
Time Frame
From baseline through to study completion, an average of 8 weeks
Title
Habitual dietary intake
Description
Habitual dietary intake will be measured two times over 3 days each using an online 24h dietary record MyFood24 prior to visit 1 and 4.
Time Frame
Before each intervention, 6 days in total
Title
Change in self-perceived stress level
Description
Participants' stress levels will be assessed using Cohen's 10-item Perceived Stress Scale (PSS) at visits 1, 3, and 6. Each item is scored on a scale from 1-5 where higher values represent a higher level of self-perceived stress.
Time Frame
At visit 1 and after each intervention
Title
Change in subjective gastrointestinal symptoms
Description
Changes in subjective gastrointestinal symptoms reported by participants on a visual analog scale from 0 to 10, where 0 means no symptoms and 10 means the worst possible symptoms. The questionnaire includes the following symptoms: overall stomach and intestinal symptoms, stomachache, flatulence, bloating, constipation, and diarrhea.
Time Frame
From visit 1 through to study completion, an average of 7 weeks
Title
Physical activity level
Description
Physical activity will be measured by the International Physical Activity Questionnaire short form (IPAQ-s) at the screening visit. The IPAQ-s consists of 7 items asking about the amount of physical activity (in minutes) at different intensities. The score is the sum of minutes of activity at each intensity level given as metabolic equivalents (METs). The higher the MET score, the more physically active the participant is.
Time Frame
At baseline
Title
Change in sleep quality
Description
Changes in sleep pattern and quality will be measured by the Pittsburg Sleep Quality Index (PSQI) at visits 1, 3, and 6. The PSQI consists of 19 items, summed into seven component scores and one overall composite score. Each item is rated on a scale from 0-3 with lower scores reflecting healthier sleep quality.
Time Frame
At visit 1 and after each intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
18.5-30.0 kg/m2 BMI
Self-reported ≤3.5 spontaneous bowel movements per week
Willing to collect urine and stool samples at home and able to temporarily store them in their own freezer in a provided container.
Willing to eat the foods provided.
Owns a smartphone (iOS 11.0 and later or Android 5.0 and up) with access to the internet.
Exclusion Criteria:
Pregnant or lactating women.
Diagnosis of irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), inflammatory bowel diseases (IBD), Gastrointestinal obstruction, or Ischemic colitis
Diagnosed constipation according to the ROME IV criteria
Intake of antibiotics ˂ 1month, or any medication that can affect the outcomes of the study
Regular use of diarrhea inhibitors or laxatives
Dysphagia
Any chronic disease that can affect the outcomes of the study or pose a risk when consuming Movicol
Intake of medications potentially altering gastric pH (proton pump inhibitors, histamine receptor antagonists, antacids)
Intake of medications potentially altering the gastrointestinal motility (prokinetics, antiemetic agents, anti-cholinergic agents, narcotic analgetics, nonsteroidal anti-inflammatory drugs, and peroral glucocorticoids)
Concurrent participation in another trial
Any condition that makes the project responsible researcher to doubt the feasibility of the volunteer´s participation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Henrik M Roager, PhD
Phone
+4535324928
Email
hero@nexs.ku.dk
Facility Information:
Facility Name
University of Copenhagen, Department of Nutrition, Exercise and Sports
City
Copenhagen
ZIP/Postal Code
1958
Country
Denmark
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henrik M Roager, PhD
Phone
+4535324928
Email
hero@nexs.ku.dk
12. IPD Sharing Statement
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Effects of Changing Intestinal Transit Time on Gut Microbial Composition and Metabolism
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