Correcting GUT microbioTa by Combined Supplementation of fibERs and bIotiN to Improve Microbiome and Optimize Bariatric Surgery Outcomes

Not Applicable

Recruiting

• Conditions: Metabolic Syndrome; Severe Obesity
• Interventions: Other: Standard of care; Dietary Supplement: Fiber supplement; Dietary Supplement: Biotin supplement

• Registration Number: NCT05832190
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2023-02-10
• Study First Submitted QC: 2023-04-14
• Study First Posted: 2023-04-27
• Study Start: 2023-07-24
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-08
• Last Update Posted: 2024-01-10
• Primary Completion: 2024-12-24
• Study Completion: 2024-12-24

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 48

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, Usual Fiber intake < 20g/day in food consumption evaluated by 24h recall
3. Signature of the informed consent
4. Effective contraception in women of childbearing age
5. Subject with health insurance (except AME)

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 3: Same usual general dietary recommendations PLUS Fiber	Fiber supplement	Patients will receive the 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 Fiber PLUS Biotin	Fiber supplement	Patients will receive the 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.
Arm 2: Same usual general dietary recommendations PLUS Biotin	Biotin supplement	Patients will receive the same usual general dietary recommendations PLUS 1 capsule per day of Biotin 450 µg per day during 3 months before the surgery.
Arm 3: Same usual general dietary recommendations PLUS Fiber	Standard of care	Patients will receive the 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 Fiber PLUS Biotin	Biotin supplement	Patients will receive the 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.
Arm 2: Same usual general dietary recommendations PLUS Biotin	Standard of care	Patients will receive the same usual general dietary recommendations PLUS 1 capsule per day of Biotin 450 µg per day during 3 months before the surgery.
Arm 1: patient with usual follow-up (standard of care)	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 4: Same usual general dietary recommendations PLUS Fiber PLUS Biotin	Standard of care	Patients will receive the 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.

Primary Outcome Measures

Name	Time	Method
3-month variation of gut microbiota richness 3 months after the start of the different dietary interventions	At the inclusion and 3 months after supplementation	Access to gut microbiota richness will be provided after gut microbiota sequencing (by INRAE) with the acquisition of a table comprising the number of genes as well as the record of bacterial genes implicated in synthesis and transport of biotin. Based on preclinical observation, it is expected that the arm 4 combining biotin and fibers will show the highest richness

Secondary Outcome Measures

Name	Time	Method
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.	At the inclusion, 3months after supplementation, 3 and 6 months after surgery	Body Weight will be obtained at each visit between 8 and 10 am using standardized procedures: Body weight will be obtained with a scale (Seca GmbH \& Co., Hamburg, Germany) in kilograms
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	At the inclusion, 3months after supplementation, 3 and 6 months after surgery	Height will be obtained with measuring scale rounded to the nearest 0.5 cm in centimeters Weight and height will be combined to report BMI in kg/m\^2
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	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Twaist circumference will be measured in centimeters at the level of the iliac crest and hip circumference at the level of the symphysis-great trochanter to the nearest 1 cm.
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.	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	IL6, sCD14, IL1b, IL10, TNF-R (pg/mL) will be measured by multiplex analysis
Assess changes in stool consistency	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Patients will be asked to answer a Bristol stool scale : the Bristol Scale has seven types of profiles, ranging from constipation (type 1 and 2) to diarrhea (type 6 and 7). Each type corresponds to a specific description of the stool.
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	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Quantitative insulin sensitivity check index (QUICKI) will be calculated according to the following formula: QUICKI= 1/\[log(fasting insulin) + log(fasting blood glucose)
Assess changes in adipose tissue gene expression for biotin-dependent carboxylases and inflammatory genes	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Adipose tissue aspiration (100 mg): measure for adipose cell size and gene expression study (5-carboxylase depending of biotin and inflammatory markers).
Assess changes in emotional eating	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Information regarding their usual lifestyle by autoquestionnaire : Dutch Eating Behaviour Questionaire ( DEBQ) : this questionnaire is composed by 33 items divided into 3 scores. Of the original 100 items, 33 will be maintained and divided into 3 scores. Each question allows for 5 possible answers rated from 0 to 5 points. The possible answers are: never (1 point), rarely (2 points), sometimes (3 points), often (4 points), very often (5 points). The scores are as follows: * Restriction score: 10 questions on the "organised" will to control one's weight.; * Emotionality score: 13 questions divided into two sub-scores, diffuse emotionality for 4 questions and definite emotionality for 9 questions; * Externality score: 10 questions For each score, if the average of the responses is higher than 30, the subject is considered respectively: restricted, emotional eating or external.
Assess changes in physical activity	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Information regarding their usual lifestyle by autoquestionnaire : Recent Physical Activity Questionnaire ( RPAQ) : * Interpretation of the physical activity (PA) level : Total sum week + weekend : * \<8.3 MET.h/week: inactive ; * From 8.3 MET.h/week: active, with the possibility of two levels: * From 8.3 to 16.7: moderate PA; * \>16.7: high PA.; * interpretation of the time spent inactive : For weekdays and weekends: * ≤7h/d: non-sedentary ; * \>7h/d: sedentary.
Assess changes in anxiety	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Information regarding their usual lifestyle by autoquestionnaire : HAD questionnaire (Hospital Anxiety and Depression questionnaire) : the HAD scale is an instrument to screen for anxiety and depressive disorders. It consists of 14 items rated from 0 to 3. Seven questions relate to anxiety (total A) and seven others to the depressive dimension (total D). (total D), thus allowing two scores to be obtained (maximum score for each score = 21).; For each of the scores (A and D): * 7 or less: no symptomatology; * 8 to 10: doubtful symptomatology; * 11 and more: definite symptomatology.
Change in intestinal permeability by LPS-binding protein dosage	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	LPS-binding protein dosage (mg/L)
Systemic measurement of B12-vitamin	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	B12 (pmol/L) will be measured by Elisa dosage from blood samples
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.	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	To predict insulin resistance, homeostatic model assessment of insulin resistance (HOMA-IR) will be calculated according to the following formula: HOMA-IR = \[fasting insulin (mU/l) x fasting blood glucose (mmol/l)\]/22.5.
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.	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Adiponectin (µg/mL) will be measured according to standard protocols using human Adiponectin /Acrp30 Quantikine ELISA kit (DRP300, R\&D Systems)
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	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	A fasting venous blood draw will be taken from a vein on the forearm to verify blood glucose (g/L) using commercial kits
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	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	A fasting venous blood draw will be taken from a vein on the forearm to verify alanine aminotransferase (ALT) (UI/L), aspartate aminotransferase (AST) (UI/L), gamma-glutamyl transferase (GGT) (UI/L), using commercial kits
Assess changes in stool inflammatory markers	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Fecal calprotectin (in µg/g of feces) will be measured through ELISA kit
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	At the inclusion, 3 month after supplementation, 3 and 6 months after surgery	For the measurement of fat mass (in kilograms and percentage of body weight), patients will undergo DEXA analysis, using the Hologic Inc. machine, QDR 4500W t using standard software (Hologic Inc., S/N 47168 VER. 11.2)
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	At the inclusion, 3 month after supplementation, 3 and 6 month after surgery	For the measurement of lean mass (in kilograms and percentage of body weight), patients will undergo DEXA analysis, using the Hologic Inc. machine, QDR 4500W t using standard software (Hologic Inc., S/N 47168 VER. 11.2)
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.	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Blood pressure (Systolic and Diastolic) will be measured three times with a mercury sphygmomanometer in the right arm, with patients in a sitting position after five minutes of rest. The average of the three measurements will be considered for analysis
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.	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Leptin (ng/mL) will be measured according to standard protocols using human Leptin ELISA Kit (MyBioSource, Cod. MBS9425103)
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	At the inclusion, 3months after supplementation, 3 and 6 months after surgery	A fasting venous blood draw will be taken from a vein on the forearm to verify triglycerides ( g/L), total cholesterol (g/L), HDL- cholesterol(g/L), LDL- cholesterol (g/L), using commercial kits
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	At the inclusion, 3 month after supplementation, 3 and 6 month after surgery	For the measurement of visceral adipose tissue mass (in kilograms and percentage of body weight), patients will undergo DEXA analysis, using the Hologic Inc. machine, QDR 4500W t using standard software (Hologic Inc., S/N 47168 VER. 11.2)
Systemic measurement of Biotin (B8),B6 and B9-vitamins	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Biotin (B8),B6 and B9 (nmol/L) will be measured by Elisa dosage from blood samples
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.	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	C-reactive protein (mg/l) will be measured by multiplex analysis
Assess changes in quality of life	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Information regarding their usual lifestyle by autoquestionnaire: SF-36 (Medical Outcome Study Short Form - 36) ranging from 0 to 100. A low score reflects a perception of poor health, loss of function, presence of pain. A high score reflects a perception of good health, an absence of functional deficit and pain
Assess changes in sleep quality	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Information regarding their usual lifestyle by autoquestionnaire : STOP band (Snoring - Tired - Observed apnea - Pressure - BMI - Age - Neck size - Gender) questionnaire: Interpretation of the STOP-BANG: The STOP-BANG score can be used to identify subjects at risk of sleep apnea (S.A.).; * Low risk of S.A.: Score from 0 to 2.; * Moderate risk of S.A.: Score of 3 to 4.; * High risk of S.A.: Score of 5 to 8, or STOP ≥ 2 and male sex, or STOP ≥ 2 and BMI \> 35, or STOP ≥ 2 and neck circumference \> 40cm.
Change in gut microbiota composition by quantitative metagenomics.	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Total fecal DNA will be extracted, sequenced by oxford nanopores technology and analysed using momr R package.
Change in intestinal permeability by Zonuline dosage	At the inclusion, 3 months after supplementation, 3 and 6 months after surgery	Zonuline dosage (ng/mL)

Trial Locations

Locations (1)

hôpital Pitié Salpêtrière; 🇫🇷 Paris, France