Clinical trial NCT05832190: Correcting GUT MicrobioTa by Combined Supplementation of FibERs and BIotiN to Improve Microbiome and Optimize Bariatric Surgery Outcomes
Official title: Correcting GUT MicrobioTa by Combined Supplementation of FibERs and BIotiN to Improve Microbiome and Optimize Bariatric Surgery Outcomes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Severe Obesity
Metabolic Syndrome
Keywords: GUT microbioTa
Supplementation
Fibers
Biotin
Microbiome
Bariatric surgery
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-04-27
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Bariatric surgery improves health outcomes with a maximal weight loss on average occurring 1 year after surgery but with dramatic between-subjects variability in weight loss (ranging from 20 to 160% excess weight loss) for reasons that remain to be elucidated.

The investigators hypothesize that targeting the 3 months pre-surgery period by a calibrated dietary intervention, with fiber enrichment and biotin, will improve gut microbiota richness and subsequently improve subjects' metabolic health that may optimize post bariatric surgery outcomes.

The study is designed as a pilot, comparative, randomized, open-label trial with 4 arms: standard of care, biotin only, fibers only, biotin + fibers.

Detailed description: This is a pilot open label study that aims to examine the efficacy of biotin supplementation with or without enriched soluble and insoluble fibers given during 3 months before the bariatric surgery, on gut microbiota composition and functional capacity to produce B vitamins (primary outcomes), compared to standard of care (e.g. patient preparation to bariatric surgery).

The study is a 4-arm clinical trial:

Arm 1: patients with usual follow-up (standard of care) receiving during 3 months before the surgery usual general dietary recommendations regarding balanced diet comprising legumes and fruits, meat or equivalent, dairy products and starch and bread Arm 2: Same usual general dietary recommendations PLUS Biotin 450 µg per day (1 capsule per day) during 3 months before the surgery.

Arm 3: Same usual general dietary recommendations PLUS 3 servings per day of PureLean® Fiber, a powdered blend of fibers and prebiotics, during 3 months before the surgery Arm 4: Same usual general dietary recommendations PLUS 3 servings per day of PureLean® Fiber and Biotin 450 µg per day (1 capsule per day), during 3 months before the surgery.

There will be two periods: period 1 during the 3 months before bariatric surgery and period 3 after bariatric surgery (usual standard of care follow-up). The 4 groups will be compared before bariatric surgery and up to 6 months afterward

Patients will receive a schedule of hospitalizations and visits before and after the surgery:

* V0: 3 months before surgery
* V1: presurgery visit, one day hospitalization
* V2: 3 months post-surgery
* V3: 6 months post-surgery
* V4:12 months post-surgery

At each visit (V0, V1, V2 , V3 and V4), will be performed as part of research:

* Adipose tissue aspiration
* Questionnaires
* Fecal samples
* Saliva samples (oral microbiota)
* Blood samples
* Urine samples This planning is part of the standard of care. The same follow-up will be performed in the 4 arms.

Patients will be called 3 times between V0 and V1 by dietician as part of research.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years and \< 60 years
2. BMI ≥ 40 kg/m² or BMI \> 35 kg/m² with at least one comorbidity belonging to metabolic syndrome (hyperglycemia (fasting glycemia \> 1g/l, Non diabetic with HbA1C\<7% without antidiabetic treatment), dyslipidemia (HDL-cholesterol \<0.5 g/l or receiving treatment against dyslipidemia), or increased blood pressure (SBP \>13, DBP\>9 or treated by antihypertensive drug)), or sleep apnoea, weight stable (less than 3 kg variation in the 2 months before
3. Usual Fiber intake \< 20g/day in food consumption evaluated by 24h recall
4. Signature of the informed consent
5. Effective contraception in women of childbearing age
6. Subject with health insurance (except AME)

Exclusion Criteria:

1. Patients receiving antibiotics (ATB) at the selection time or within the 2 previous months.

   (if agreeing to participate to the study, the patients will be proposed randomization 3 months after stopping ATB)
2. Type 1 or type 2 diabetes
3. HIV, HBV, HCV
4. Gastrointestinal disease: Acute or chronic diarrhea (i.e. more than 3 liquid or fluid stools/day)
5. Previous history of gastrointestinal neoplasia or polyps
6. Factors that may affect the composition of the intestinal microbiota: Special Diet (exclusion diet, vegetarian diet), taking immunosuppressants (eg calcineurin inhibitors, corticosteroids, biological agents, etc.), taking transit modulators (osmotic or prebiotics such as lactulose).
7. Pregnancy or breastfeeding women
8. Subject under guardianship or curatorship
9. Subject deprived of their liberty by a judicial or administrative decision
10. Patient participating to another interventional clinical research (Jardé 1)
11. Subject physically unable to give his or her written consent

Primary outcomes:
measure: 3-month variation of gut microbiota richness 3 months after the start of the different dietary interventions
timeFrame: At the inclusion and 3 months after supplementation
Secondary outcomes:
measure: Assess changes in body weight between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery.
timeFrame: At the inclusion, 3months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in BMI between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in waist circumference between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in fat mass between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3 month after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in lean mass between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3 month after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in visceral adipose tissue mass between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3 month after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in blood pressure between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery.
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in insulin resistance markers between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery.
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in insulin sensitivity markers between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess change in Leptin between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery.
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess change in Adiponectin between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery.
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in glucose between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in lipid profile between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in liver function between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess change in inflammatory marker (C-reactive protein) between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery.
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in inflammatory markers (IL6, sCD14, IL1b, IL10, TNF-R) between the visit 3 months before surgery and the pre-surgery visit, the visit at 3 and 6 months after surgery.
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in adipose tissue gene expression for biotin-dependent carboxylases and inflammatory genes
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in quality of life
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in emotional eating
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in physical activity
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in anxiety
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in sleep quality
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in stool consistency
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Assess changes in stool inflammatory markers
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Change in gut microbiota composition by quantitative metagenomics.
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Change in intestinal permeability by Zonuline dosage
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Change in intestinal permeability by LPS-binding protein dosage
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Systemic measurement of Biotin (B8),B6 and B9-vitamins
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
measure: Systemic measurement of B12-vitamin
timeFrame: At the inclusion, 3 months after supplementation, 3, 6 and 12 months after surgery
Other outcomes:
Locations:
city: Paris
country: France
facility: hôpital Pitié Salpêtrière
Study officials:
References: