Personalized Modulation of Microbiota (NUTRIBIOTA)

• ClinicalTrials.gov Identifier: NCT04799223
• Recruitment Status: Completed
• First Posted: March 16, 2021
• Last Update Posted: February 3, 2023
• Sponsor: Clinica Universidad de Navarra, Universidad de Navarra
• Information provided by (Responsible Party): Fermín Milagro Yoldi, Clinica Universidad de Navarra, Universidad de Navarra

Study Description

Brief Summary:

Intestinal flora or microbiota is the group of bacteria that live in the intestine, in a symbiotic relationship with the human body. It is estimated that human beings have around 2,000 different bacteria species. The gut microbiota plays a key in many of the body's functions. Hence, the analysis of the gut microbiome provides insight into the state of the microbiota as an indicator of overall health due to its metabolic, protective and nutritional functions. A balanced diet promotes the formation and maintenance of a well-structured microbiota, in which the different species of microorganisms cohabit in a balanced and controlled system.

The study is based on the hypothesis that the intake of certain plant-based foods rich in various active ingredients (especially non-digestible carbohydrates, certain types of fats and polyphenols) can modulate the microbiota and thus improve the health status of the human population.

Taking into account this background, the objective of this study is to assess the effect of the inclusion of functional foods and ingredients within a balanced diet on the composition of the microbiota and also on health parameters associated with metabolic disease.

Condition or disease	Intervention/treatment	Phase
Obesity; Microbial Colonization; Nutrition Disorders	Other: Four-foods eating guidelines; Other: No designed-foods eating guidelines	Not Applicable

Detailed Description:

The 60 volunteers participating in the study who meet the inclusion criteria, will be randomly divided into two groups:

• Control group (nutritional promotion): volunteers will be provided with basic nutritional recommendations based on a Mediterranean diet.
• Experimental group (Nutribiota): volunteers will be instructed to follow a dietary strategy similar to the control group, but including the functional foods and ingredients developed by the companies with the aim to promote a balanced and specific diet associated with improvements in the composition of the microbiota and metabolic parameters of the volunteers.

The duration of the study are 8 weeks, during which 4 visits are scheduled:

• Recruitment: this visit will consist on an initial screening in which the volunteers will be informed about the characteristics of the study and will be receive the information sheet and the informed consent form to be signed by all those interested in participating in the study. Volunteers who meet the inclusion for the study will be asked to complete the Food Frequency Questionnaire and Physical Activity Questionnaire for the next visit (visit 1). In addition, each participant will be provided with a faecal microbiota sample collection kit which they will have to hand in with the corresponding sample at the next visit (visit 1).
• Clinical investigation day 1 (week 0):after a fasting period of at least 10 hours, the nursing staff will take a blood sample to analyze the biochemical parameters and metabolomic profile. Anthropometric measurements will be taken from each volunteer (weight, height, waist and hip circumference, and body composition analysis by bioimpedance) with the collaboration of a dietician. In addition, faecal sample and Food Frequency Questionnaire and Physical Activity Questionnaire will be collected. Volunteers randomly assigned to the experimental group will be given the dishes and functional ingredients designed by the companies, which they will have to incorporate into a balanced dietary pattern following the indications given by the dietician.
• Clinical investigation day 2 (week 4): In this visit, the adherence of the volunteers to the study will be monitored and the weight of the volunteers will be registered. In addition, all study volunteers will be given a faecal microbiota sample collection kit, which should be handed in with the corresponding sample at the final visit. Moreover, Food Frequency Questionnaire and Physical Activity Questionnaire will be given to each volunteer in order to be filled for the final visit. Volunteers who belong to the experimental group will be given dishes and functional ingredients.
• Clinical investigation day 3 (week 8): Faecal sample, Food Frequency Questionnaire and Physical Activity Questionnaire will be collected. The procedures in this visit will be the same as in visit 1, but dishes and functional ingredients will not be given to the volunteers.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Personalized Modulation of the Microbiota Through the Intelligent Design of Foods and Ingredients Based on Enterotype-Based Diagnosis (NUTRIBIOTA). Nutritional Intervention in Humans
• Actual Study Start Date: November 15, 2020
• Actual Primary Completion Date: March 30, 2021
• Actual Study Completion Date: May 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group receiving the 4 designed foods; The experimental group consumes the 4 foods designed for the study and will follow healthy eating guidelines.	Other: Four-foods eating guidelines; To follow a healthy eating pattern and consume four (4) foods designed for the study (extra virgin olive oil with olive leaf extract, chickpea dish with spinach, vegetable cream dish, and olive fiber) and to follow a healthy eating pattern.
Active Comparator: Group with no designed foods; The control group follows healthy eating guidelines.	Other: No designed-foods eating guidelines; To follow a healthy eating pattern. Their diet is not accompanied by the four newly designed foods of the other group.

Outcome Measures

Primary Outcome Measures :

1. Change of fecal microbiota composition [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]

   Measured by analyzing the variable regions V3-V4 of the prokaryotic 16S rRNA (ribosomal ribonucleic acid) gene sequences, which gives 460 bp amplicons in a two-round PCR protocol. The kit used will be the Nextera® XT DNA Index Kit, FC-131-1002 (Illumina, San Diego, CA, USA).

   In the first step, PCR is used to amplify a template out of a DNA fecal sample using specific primers from Illumina. Then, sequencing libraries are built with the MiSeq® Reagent Kit v3 (600 cycles) MS-102-3003 (Illumina). Finally, paired-end sequencing is performed on a MiSeq platform (Illumina) with a 600 cycles Miseq run.

   Fecal samples are self-collected by the volunteers' fecal samples using OMNIgene.GUT kits from DNA Genotek (Ottawa, ONT, Canada), according to the standard instructions provided by the company

Secondary Outcome Measures :

1. Change of glucose concentration [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
   Glucose concentration will be reported in mg/dl
2. Change of total cholesterol concentration [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
   Total cholesterol concentration will be reported in mg/dl
3. Change of LDL-cholesterol concentration [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
   LDL-cholesterol concentration will be reported in mg/dl by Friedewald equation.
4. Change of HDL-cholesterol concentration [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
   HDL-cholesterol concentration will be reported in mg/dl
5. Change of triglyceride concentration [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
   Triglyceride concentration will be reported in mg/dl
6. Change of aspartate aminotransaminase concentration [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
   Aspartate aminotransaminase concentration will be reported in mg/dl
7. Change of alanine aminotransferase concentration [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
   Alanine aminotransferase concentration will be reported in U/L
8. Change of insulin concentration [ Time Frame: Clinical The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention).day 1 and 3 ]
   Insulin concentration will be reported in U/L
9. Change of body weight [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
   Body weight will be reported in kg
10. Change of body mass index [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
    Body weight will be reported in kg
11. Change of body fat mass percentage [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
    Body fat mass will be reported in percentage
12. Change of body lean mass [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
    Body lean mass will be reported in kg
13. Change of body water percentage [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
    Body water will be reported in percentage
14. Change of visceral fat level [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
    Visceral fat level will be reported
15. Change of physical activity [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
    Physical activity level will be monitored by physical activity questionnaire
16. Change of dietary intake [ Time Frame: The Time Frame contains two time points: day 1 (at baseline) compared to day 3 (after 8 weeks of dietary intervention). ]
    Dietary energy and macronutrient intake will be monitored by a food frequency questionnaire

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Volunteers of both sexes with ages between 20 and 65 years.
• Volunteers with a body mass index between 24.9 and 34.9 kg / m2.
• Volunteers with intestinal dysbiosis.
• Physical examination and normal vital signs or clinically irrelevant for the study.
• Subjects must be able to understand and be willing to sign the informed consent.

Exclusion Criteria:

• Volunteers who have taken antibiotics or corticosteroids one month before the start of the intervention or antihistamines 15 days before the start of the intervention.
• Volunteers who are taken gastric protectors chronically.
• Volunteers who present changes in their pharmacological treatment in the last 3 months before the start of the study.
• Volunteers with intestinal pathologies (ulcerative colitis, Crohn's disease, or similar).
• Volunteers suffering from Covid-19

Contacts and Locations

Locations

Spain

Center for Nutrition Research. University of Navarra

Pamplona, Navarra, Spain

Sponsors and Collaborators

Clinica Universidad de Navarra, Universidad de Navarra

Investigators

• Principal Investigator: Fermín Milagro Yoldi, PhD; University of Navarra

More Information

• Responsible Party: Fermín Milagro Yoldi, Principal Investigator, Clinica Universidad de Navarra, Universidad de Navarra
• ClinicalTrials.gov Identifier: NCT04799223
• Other Study ID Numbers: NUTRIBIOTA
• First Posted: March 16, 2021
• Last Update Posted: February 3, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fermín Milagro Yoldi, Clinica Universidad de Navarra, Universidad de Navarra:

Obesity; Fecal microbiota; Nutrition; Diet; Insulin

Additional relevant MeSH terms:

Communicable Diseases; Infections; Nutrition Disorders; Disease Attributes; Pathologic Processes