Effects of Changing Intestinal Transit Time on Gut Microbial Composition and Metabolism

Metabolic Disease Clinical Trial

— 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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06022302
• Other study ID #: M245
• Status: Recruiting
• Phase: N/A
• Start date: October 3, 2023
• Est. completion date: January 2030

Study information

• Verified date: November 2023
• Source: University of Copenhagen
• Contact: Henrik M Roager, PhD
• Phone: +4535324928
• Email: hero[@]nexs.ku.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 2030
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diet, Healthy
• Metabolic Disease
• Metabolic Diseases

Intervention

Drug:
• Diet + laxative
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.

Other:
• Diet only
This is only a control and participants will not receive Movicol.

Locations

Country	Name	City	State
Denmark	University of Copenhagen, Department of Nutrition, Exercise and Sports	Copenhagen

Sponsors (4)

Lead Sponsor	Collaborator
University of Copenhagen	KU Leuven, Technical University of Denmark, University of Minnesota

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Urine metabolome as assessed by untargeted metabolomics	Changes in the urine metabolome between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Blood metabolome as assessed by untargeted metabolomics	Changes in the blood metabolome between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Fecal microbial metabolites of proteolytic fermentation measured by mass spectrometry	Assessment of changes in fecal microbial metabolites of proteolytic fermentation (amino acid-derived metabolites).	From visit 1 through to study completion, an average of 7 weeks
Other	Fecal enzymatic activities	Assessment of changes in enzymatic activities measured in fecal samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Fecal residual carbohydrate concentration	Change in residual carbohydrate concentration measured in fecal samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Fecal energy density	Change in fecal energy density measured by bomb calorimetry in fecal samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Fecal redox potential measured in mV	Change in redox potential measured in fecal samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Fecal carbon:nitrogen (C:N) ratio	Change in C:N ratio measured in fecal samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Fecal microbial load (cells per gram)	Change in microbial load in fecal samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Fecal calprotectin concentration	Change in concentration of calprotectin measured in fecal samples between interventions. Used as a measure of intestinal inflammation.	From visit 1 through to study completion, an average of 7 weeks
Other	Change in various markers related to glucose metabolism	Changes in the concentration of various standard markers of glucose metabolism in fasting blood samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Change in various markers related to lipid metabolism	Changes in concentration of various standard biochemical markers of lipid metabolism in fasting blood samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Change in various markers of inflammation	Change in concentration of various inflammatory markers in fasting blood between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Change in various appetite hormones	Change in concentration of various appetite hormones in fasting blood between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Urinary creatinine concentration	Measurement of urinary levels of creatinine from spot urine samples between interventions.	From visit 1 through to study completion, an average of 7 weeks
Other	Amylase gene copy number	Measurement of amylase gene copy numbers from blood samples at visit 1 to determine the phenotype of the participants.	At visit 1
Other	Change in body weight	Change in body weight is measured using a calibrated digital scale to ensure/monitor weight stability throughout the study.	From baseline through to study completion, an average of 8 weeks
Other	Measurement of breath hydrogen and methane profiles in parts per million (Area under the curve)	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.	From baseline through to study completion, an average of 8 weeks
Other	Habitual dietary intake	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.	Before each intervention, 6 days in total
Other	Change in self-perceived stress level	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.	At visit 1 and after each intervention
Other	Change in subjective gastrointestinal symptoms	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.	From visit 1 through to study completion, an average of 7 weeks
Other	Physical activity level	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.	At baseline
Other	Change in sleep quality	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.	At visit 1 and after each intervention
Primary	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.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Whole gut transit time measured by sweet corn	Changes in whole gut transit time between interventions determined by the passage time of sweet corn.	From visit 1 through to study completion, an average of 7 weeks
Secondary	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.	From visit 1 through to study completion, an average of 7 weeks
Secondary	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.	From visit 1 through to study completion, an average of 7 weeks
Secondary	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.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Fecal water content in percentage of stool weight	Change in fecal water content between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Fecal concentration of short-chain fatty acids	Change in concentration of short-chain fatty acids between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Fecal pH	Change in fecal pH level between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Fecal ammonia concentration	Change in ammonia content between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Concentration of fasting plasma short-chain fatty acids	Change in concentration of short-chain fatty acids between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Fasting plasma concentrations of bile acids	Change in concentration of bile acids in fasting blood between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	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.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Microbial metabolites in urine from proteolytic fermentation as assessed by mass spectrometry	Changes in the urine concentration of metabolites of microbial proteolysis between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Microbial metabolites in blood from proteolytic fermentation as assessed by mass spectrometry	Changes in the blood concentration of metabolites of microbial proteolysis between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Fecal metabolome as assessed by untargeted metabolomics	Changes in the fecal metabolome between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Gut microbiome assessed by shotgun sequencing	Changes in gut microbiota composition between interventions.	From visit 1 through to study completion, an average of 7 weeks
Secondary	Gut microbiome assessed by 16S amplicon sequencing	Changes in gut microbiota composition between interventions.	From visit 1 through to study completion, an average of 7 weeks