The Impact of Hafnia Alvei on Weight Loss and Glycaemic Control After Bariatric Surgery

Study Overview
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Brief Summary
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This study aims to investigate the effects of Hafnia alvei HA4597 TM supplementation on weight loss and glycemic control after bariatric surgery. Patients undergoing Roux-en-Y gastric bypass will receive probiotics or placebo, twice a day, for 60 days, one month after surgery. Outcomes will be measured at baseline, and 1, 3, 6, 9 and 12 months after the surgery.

Detailed Description
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Gut microbiota dysbiosis is associated with the pathophysiology of obesity. Bariatric surgery is an effective treatment for obesity that induces changes in the gut microbiota. However, recent studies indicate that the gut microbiota is not fully restored after bariatric surgery which may limit the potential of the surgery to achieve metabolic control and maintain weight loss. Thus, modulating the gut microbiota with probiotics after bariatric surgery could be an effective strategy to improve the success of the surgery. This study aims to investigate the effects of Hafnia alvei HA4597 TM supplementation on weight loss and glycemic control after bariatric surgery. Patients undergoing Roux-en-Y gastric bypass will receive probiotics or placebo, twice a day, for 60 days, one month after surgery. Outcomes will be measured at baseline, and 1, 3, 6, 9 and 12 months after the surgery.

Official Title
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The Impact of Hafnia Alvei on Weight Loss and Glycaemic Control After Bariatric Surgery - A Randomized, Triple-blind, Controlled Trial

Conditions
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Obesity, Type 2 Diabetes

Intervention / Treatment
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* Dietary Supplement: Hafnia alvei HA4597™
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between 18 and 65 years BMI ≥35 kg/m2 and at least one severe obesity-related complications, or BMI ≥40 kg/m2 Undergoing Roux-en-Y gastric bypass Willing to take a probiotic/placebo supplement twice a day for 60 days Willing and able to provide written informed Exclusion Criteria: Intake of antibiotics and/or probiotics in the previous 12 weeks Weight change >5% in the previous 12 weeks Diagnosis of gastrointestinal disease or other significant illness Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic group<br>Two capsules of Hafnia alvei HA4597™ probiotic/day (5 x 107 CFU/day) for 60 days | Dietary Supplement: Hafnia alvei HA4597™<br>* One capsule of probiotic supplement, twice a day, to be taken with water, during each breakfast and lunch (approx. 5 minutes after starting eating), for 60 days. Two capsules of the dietary supplement contain 5x107 CFU of Hafnia alvei HA4597™, 5 mg of zinc and 20 μg of chromium.<br>|
| Placebo Comparator: Placebo group<br>Two identical capsules of placebo/day for 60 days | Other: Placebo<br>* One capsule of placebo, twice a day, to be taken with water, during each breakfast and lunch (approx. 5 minutes after starting eating), for 60 days. Two capsules of the placebo contain 5 mg of zinc and 20 μg of chromium.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Excess weight loss | Changes in percentage of excess weight loss from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| HbA1c | Changes in HbA1c levels (%) from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota | Changes in gut microbiota from baseline. Bacterial DNA will be extracted from faecal samples. 16S rRNA gene will be sequenced by next-generation sequencing (NGS). All the identified bacterial phyla, genus and species will be expressed in percentage. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Gastrointestinal quality of life | Changes in gastrointestinal quality of life by the Gastrointestinal Quality of Life Index (GIQLI) questionnaire from baseline. The GIQLI is a 36 -item questionnaire and consists of 5 different subscales. The total score is calculated as the sum of the 36 items each ranged from 0 to 4. The final score range from 0 to 144 points (lower scores indicate more unfavorable conditions). | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Caseinolytic protease B | Changes in caseinolytic protease B (pM) from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Gut microbiota metabolites | Changes in short-chain fatty acids (acetate, propionate and butyrate) concentrations (mg/mL) from baseline. Short-chain fatty acids will be measured by targeted metabolomics. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Fasting blood glucose | Changes in fasting blood glucose levels (mg/dL) levels from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Insulin | Changes in insulin levels (μU/mL) levels from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| C-peptide | Changes in c-peptide levels (ng/mL) levels from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Total cholesterol | Changes in total cholesterol levels (mg/dL) from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| HDL cholesterol | Changes in high-density lipoprotein (HDL) cholesterol (mg/dL) levels from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| LDL cholesterol | Changes in low-density lipoprotein (LDL) cholesterol (mg/dL) levels from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Triacylglycerides | Changes in triacylglycerides (mg/dL) levels from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Body fat mass | Changes in percentage of body fat mass from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Free fat mass | Changes in free fat mass (kg) from baseline. | At visit 1 (Baseline), visit 2 (1 month after bariatric surgery), visit 3 (3 months after bariatric surgery), visit 4 (6 months after bariatric surgery), visit 5 (9 months after bariatric surgery), visit 6 (12 months after bariatric surgery). | 
| Proportion of subjects losing more than 50% of baseline excess weight | Percentage of subjects losing >50% of baseline excess weight from baseline to visit 6 (12 months after bariatric surgery). | At visit 1 (Baseline), visit 6 (12 months after bariatric surgery). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Gut microbiota, Probiotics