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Luxembourgish Fiber Cohort (Lux-FiCo)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04352231
Recruitment Status : Recruiting
First Posted : April 20, 2020
Last Update Posted : February 24, 2022
Sponsor:
Collaborators:
Centre Hospitalier du Luxembourg
Integrated Biobank of Luxembourg
Luxembourg Centre for Systems Biomedicine
Information provided by (Responsible Party):
Luxembourg Institute of Health

Brief Summary:
Many human populations across the world are deficient in the intake of dietary fiber. This decline in fiber consumption parallels an increase in prevalence of a multitude of diseases (e.g. colorectal cancer, multiple sclerosis). A possible link for this association between dietary changes and the diseases could rest in the trillions of commensal gut microbes that digest dietary fibers, provide energy for colonic cells, and modulate the immune system. However, the molecular mechanisms that link fiber deficiency via the activities of the gut microbiome to various diseases have been poorly understood. The investigators previously showed that, in a mouse model with a defined human gut microbiota, removal of fiber from the diet favors proliferation of bacteria that degrade the gut's protective mucus lining. In the proposed project, the investigators aim to translate our findings from mouse studies to humans using a 2x2 crossover study among healthy adults. Forty participants will be randomly assigned to a low- or high-fiber dietary intervention and then, following a washout period to reverse any changes, switched to the other diet type. By employing longitudinal sampling of stool collections, the investigators envision that participants will exhibit increased abundance and activities of mucolytic bacteria when fed a low-fiber diet. The unique selling point of the proposed study involves setting up high-throughput culture collections of mucus-degrading bacteria, whose abundances and activities will be investigated by sequencing and enzymatic assays in stool. Additionally, the investigators will measure inflammatory markers in blood using CyTOF to assess whether short-term fiber deficiency exerts detectable changes in the host immune function. Thus, the proposed dietary intervention clinical trial will help elucidate the role of fiber deficiency in various chronic diseases.

Condition or disease Intervention/treatment Phase
Dietary Fiber Gastrointestinal Microbiome Healthy Volunteers Dietary Supplement: High Fiber Diet Intervention Dietary Supplement: Low Fiber Diet Intervention Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This study involves recruitment of healthy volunteers to participate in a 2x2 crossover design controlled-diet study.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: From Mouse to Man: Translating Findings in Mouse Study Into a Human Cohort (Luxembourgish Fiber Cohort: Lux-FiCo)
Actual Study Start Date : February 22, 2021
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dietary Fiber

Arm Intervention/treatment
Experimental: High to Low Fiber Diet Intervention
Participants receive the high fiber diet intervention first, then undergo a washout period to reverse any changes from the diet before receiving the low fiber diet intervention. A second washout period will follow this diet so that we can track any reversal of diet-linked changes.
Dietary Supplement: High Fiber Diet Intervention
Plant-based diet with a targeted quantity of 35 g of dietary fiber per day, from a variety of fiber types. Each meal will be balanced to provide all essential nutrients and portions will be of adequate size to ensure participants are satiated. Participants on both diet interventions will be given multivitamin supplements in order to ensure they are receiving essential vitamins and minerals.

Dietary Supplement: Low Fiber Diet Intervention
Animal based diet (meat, dairy) with a targeted quantity of 10 g of dietary fiber per day. Each meal will be balanced to provide all essential nutrients and portions will be of adequate size to ensure participants are satiated. Participants on both diet interventions will be given multivitamin supplements in order to ensure they are receiving essential vitamins and minerals.

Experimental: Low to High Fiber Diet Intervention
Participants receive the low fiber diet intervention first, then undergo a washout period to reverse any changes from the diet before receiving the high fiber diet intervention. A second washout period will follow this diet so that we can track any reversal of diet-linked changes.
Dietary Supplement: High Fiber Diet Intervention
Plant-based diet with a targeted quantity of 35 g of dietary fiber per day, from a variety of fiber types. Each meal will be balanced to provide all essential nutrients and portions will be of adequate size to ensure participants are satiated. Participants on both diet interventions will be given multivitamin supplements in order to ensure they are receiving essential vitamins and minerals.

Dietary Supplement: Low Fiber Diet Intervention
Animal based diet (meat, dairy) with a targeted quantity of 10 g of dietary fiber per day. Each meal will be balanced to provide all essential nutrients and portions will be of adequate size to ensure participants are satiated. Participants on both diet interventions will be given multivitamin supplements in order to ensure they are receiving essential vitamins and minerals.




Primary Outcome Measures :
  1. Change in gut microbiota composition across study periods [ Time Frame: through study completion, an average of 1 month ]
    Assessment of whether statistically significant shifts in the community composition has occurred will be performed using PERMANOVA on the SILVA-annotated taxonomic output of 16S rRNA gene sequence data from stool taken on the last three days of each intervention. Visual presentation of beta-diversity will be presented using PCoA plots based on weighted and unweighted Unifrac distance measures.


Secondary Outcome Measures :
  1. Change in gut microbiota CAZyme abundance across study periods [ Time Frame: through study completion, an average of 1 month ]
    Abundance of carbohydrate active enzymes (CAZymes) detected by shotgun sequencing of genomic DNA isolated from stool. Main comparison will be between high and low fiber diet intervention periods.

  2. Change in gut microbiota mucolytic enzyme activity across study periods [ Time Frame: through study completion, an average of 1 month ]
    Average bacterial sulfatase enzymatic activity of samples taken turing the last 3 days of each study period. Main comparison will be the average activity levels between high and low fiber diet intervention periods.


Other Outcome Measures:
  1. Change in fecal acetate levels across study periods [ Time Frame: through study completion, an average of 1 month ]
    Acetate concentrations by mass spectrophotometry over last 3 days of each study period.

  2. Change in fecal propionate levels across study periods [ Time Frame: through study completion, an average of 1 month ]
    Propionate concentrations by mass spectrophotometry over last 3 days of each study period.

  3. Change in fecal butyrate levels across study periods [ Time Frame: through study completion, an average of 1 month ]
    Butyrate concentrations by mass spectrophotometry over last 3 days of each study period.

  4. Change in CyTOF immune profiles across study periods [ Time Frame: through study completion, an average of 1 month ]
    Changes to the immune cell populations, profiled using Time of Flight Mass Cytometry (CyTOF).

  5. Change in CRP across study periods [ Time Frame: through study completion, an average of 1 month ]
    Changes to levels of C reactive protein (CRP), a general inflammatory marker, assayed using ELISA kits.

  6. Change in LCN2 across study periods [ Time Frame: through study completion, an average of 1 month ]
    Changes to levels of lipocalin-2 (LCN2), a general inflammatory marker, assayed using ELISA kits.

  7. Change in calprotectin across study periods [ Time Frame: through study completion, an average of 1 month ]
    Changes to levels of calprotectin, a general inflammatory marker, assayed using ELISA kits.

  8. Change in fasting glucose level across study periods [ Time Frame: through study completion, an average of 1 month ]
    Changes to levels of fasting glucose assayed by a commercial lab.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or female:

    a. The investigators will aim for a 50:50 male:female ratio, at most 40:60. Therefore, given a sample size of N=40, if 24 eligible participants are exceed for one gender, the investigators will proceed with recruitment only for members of the underrepresented gender.

  2. Between 18 and 35 years of age (expand to 55 if needed)
  3. BMI between 18.5 ≥ BMI > 25 kg/m2 (expand to 30 if needed)
  4. Born in Europe
  5. Current resident of Luxembourg City or Esch-sur-Alzette (expand to nearby communes if needed)
  6. Own a smartphone with access to Android or Apple Store applications

Exclusion Criteria:

  1. Following a specific diet or subject to dietary restrictions for any reason
  2. "Vigorous" physical activity level based on the International Physical Activity Questionnaire - Short Form (IPAQ-SF) criteria
  3. Antibiotics usage within the past 3 months
  4. Probiotics usage within the past 1 month
  5. Laxatives usage within the past 1 month
  6. Other regular medication usage (e.g. ibuprofen, warfarin)
  7. Current or former smoker
  8. Gastrointestinal disorder (e.g. ulcerative colitis, Crohn's disease) diagnosis
  9. History of gastrointestinal surgery (excluding appendectomy)
  10. Metabolic disorder diagnosis or predisposition (determined by blood test at eligibility screen)

    1. Prediabetes: fasting glucose 100-125 mg/dL (6.1-7.0 mmol/L) and/or drug treatment of elevated glucose (8)
    2. Diabetes: fasting glucose ≥126 mg/dL (7.0 mmol/L) and/or drug treatment of elevated glucose and/or previously diagnosed type 1 or type 2 diabetes (8)
    3. Hypertriglyceridaemia: fasting triglycerides ≥1.7 mmol/L (≥150 mg/dL) and/or drug treatment for elevated triglycerides (9)
    4. Hypercholesterolaemia: Fasting High-density lipoprotein cholesterol (HDL-C) < 40 mg/dL (< 1.0 mmol/L) in men and < 45 mg/dL (< 1.2mmol/L) in women and/or drug treatment for reduced HDL-C (9)
    5. Hypertension: Systolic BP ≥130 and/or diastolic BP ≥80 mm Hg and/or drug treatment of previously diagnosed hypertension (10)
  11. Cancer (any type) diagnosis (note that a history of cancer that has been in remission for >3 years may still be considered eligible)
  12. Immunodeficiency disorder (e.g. HIV) or autoimmune disorder (e.g. rheumatoid arthritis, lupus) diagnosis
  13. Neurological disorder (e.g. advanced dementia, diagnosed major depressive disorder or generalized anxiety disorder)
  14. Coagulation problems (e.g. hemophilia) or anemia impacting ability to participate in blood draw
  15. Circulatory disorder (e.g. ischemic heart diseases or history of stroke)
  16. Currently pregnant or lactating (breastfeeding)
  17. Vacation planned during study period
  18. Moving out of Luxembourg during the study period
  19. Potential conflict of interest: involved in study design, administration, data analysis, or publication of findings or belonging to the lab group of the study's principal investigators

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04352231


Contacts
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Contact: Erica T Grant, MPH +352 26970-271 erica.grant@lih.lu
Contact: Manon Gantenbein (CIEC), PhD +352 26970-807 manon.gantenbein@lih.lu

Locations
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Luxembourg
Luxembourg Institute of Health Recruiting
Esch-sur-Alzette, Luxembourg, 4354
Contact: Erica T Grant, MPH    661522722    erica.grant@lih.lu   
Contact: Manon Gantenbein, PhD    +352 26970-807    manon.gantenbein@lih.lu   
Principal Investigator: Mahesh S Desai, PhD         
Sub-Investigator: Carine De Beaufort, MD         
Sub-Investigator: Torsten Bohn, PhD         
Sub-Investigator: Markus Ollert, MD         
Sub-Investigator: Erica T Grant, MPH         
Sub-Investigator: Hanen Samouda, PhD         
Sub-Investigator: Manon Gantenbein, PhD         
Sub-Investigator: Michel Vaillant, PhD         
Luxembourg Institute of Health Recruiting
Strassen, Luxembourg, 4356
Contact: Erica T Grant, MPH    +352 26970-271    erica.grant@lih.lu   
Contact: Manon Gantenbein, PhD    +352 26970-807    manon.gantenbein@lih.lu   
Principal Investigator: Mahesh S Desai, PhD         
Sub-Investigator: Carine De Beaufort, MD         
Sub-Investigator: Torsten Bohn, PhD         
Sub-Investigator: Markus Ollert, MD         
Sub-Investigator: Erica Grant, MPH         
Sub-Investigator: Hanen Samouda, PhD         
Sub-Investigator: Manon Gantenbein, PhD         
Sub-Investigator: Michel Vaillant, PhD         
Sponsors and Collaborators
Luxembourg Institute of Health
Centre Hospitalier du Luxembourg
Integrated Biobank of Luxembourg
Luxembourg Centre for Systems Biomedicine
Investigators
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Principal Investigator: Mahesh S Desai, PhD Luxembourg Institute of Health
Publications:

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Responsible Party: Luxembourg Institute of Health
ClinicalTrials.gov Identifier: NCT04352231    
Other Study ID Numbers: LUX-FICO
First Posted: April 20, 2020    Key Record Dates
Last Update Posted: February 24, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Sequencing data from microbiome samples and isolates will be uploaded to public repositories (ENA/EBI). Pseudonymized participant data will also be shared with collaborators and may be available to other researchers upon request and based on the participants sharing preferences as indicated in the consent form.
Time Frame: Data will become available to share with other researchers at the time of publication. Accession numbers for sequencing data will be published in the manuscript.
Access Criteria: All IPD will be pseudonymised. Researchers requesting use of this data should make an inquiry by email to the Principal Investigator explaining the purpose of their proposed work and what types of metadata they are interested in before any data sharing can be approved. In keeping with data minimization policies, we will share only the data that is relevant for the proposed analyses. Furthermore, data may not be shared if the participant has indicated on their consent form that they do not wish their data to be used in follow up studies (in the same or a different field of research).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Luxembourg Institute of Health:
Metagenome
Whole Genome Sequencing
Biomarkers
Mucolytic Activity
Mass cytometry
Inflammatory Bowel Diseases