Targeting Obesity With the Probiotic Lactiplantibacillus Plantarum IMC 510 (PRO-Weight-Control Study)

Sponsor

Azienda Ospedaliero-Universitaria Careggi (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05358301

Collaborator

(none)

Enrollment

Location

Arms

8.8

Anticipated Duration (Months)

4.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In recent decades, the prevalence of obesity has reached epidemic proportions, with the number of overweight or obese individuals continuing to increase worldwide. Advances in recent research have allowed a better characterization of the etiology of obesity, demonstrating the involvement of the gut microbiota. In fact, while signals from the brain influence gut function, the gut microbiota has been shown to modulate brain functions involved in the regulation of stress, depression and anxiety, which are closely linked to obesity. Oral administration of probiotics has been proposed as a valid way to modulate the gut ecosystem to promote weight reduction. Preliminary data showed that obese rats treated with probiotics containing the probiotic strain Lactiplantibacillus Plantarum IMC 510 exhibited significantly lower weight and food intake than untreated obese rats. Although exercise and diet are the first lines of intervention to be recommended, there are often failures or poor outcomes. There is currently increased interest in alternative and effective shorter-term, non-pharmacological approaches to weight control that involve the use of natural active ingredients. Thus, the aim of this intervention study is to investigate whether a probiotic supplementation with Lactiplantibacillus Plantarum IMC 510 could be beneficial for the weight reduction of people with obesity.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Dietary Supplement: Probiotic Dietary Supplement: Placebo	N/A

Detailed Description

Background

Obesity is a multifactorial disease characterized by a chronic imbalance between energy intake and energy expenditure. Risk factors for weight excess are genetic, metabolic, hormonal, psychological, and social, as well as factors related to diet, sedentary lifestyle, and medication intake. Obesity is associated with an increased risk of onset of several metabolic diseases (high blood pressure, dyslipidemia, diabetes mellitus, metabolic syndrome), cardiovascular diseases (cerebral strokes, myocardial infarction), gastrointestinal diseases (esophageal reflux, cholelithiasis, pancreatitis, hepatopathy), respiratory diseases (apnea, respiratory failure), cancer (higher incidence of cancer and worsening of prognosis), osteoarticular diseases (osteoporosis, osteoarthritis), psychological diseases (depression, low self-esteem, relationship problems).

In recent decades, the prevalence of obesity has reached epidemic proportions. In fact, current data estimate that approximately 600 million people worldwide are obese, with an additional 1.9 billion overweight. Moreover, recent trend analyses show that the number of individuals who are overweight or obese continues to increase worldwide.

Advances in recent research have allowed for better characterization of the etiology of obesity, highlighting the potential contribution of factors not traditionally considered to be involved in changes in energy balance and body composition. Experimental and clinical studies have also demonstrated the role of the gut microbiota in the regulation of energy balance and the occurrence of excess body weight. In this regard, it has been suggested that lean and obese human subjects differ in the composition of their gut microbiota, and that probiotics and prebiotics can be used to modify the microbiota to prevent body weight gain. The bidirectional gut-brain connection allows signals from the brain to influence motility, appetite sensations, secretions, and permeability of the gut. Studies have demonstrated the role and importance of the gut microbiota in modulating central nervous system activity, so some gut messages may influence brain functions involved in the regulation of stress, depression, and anxiety, which are closely related to obesity. Consequently, the gut microbiota is a potential modifiable target for the prevention and/or treatment of obesity. In fact, the gut microbiota has recently been shown to play a complex role in body weight regulation and some probiotic strains have been able to ameliorate obesity status and related metabolic disorders. Preliminary data showed that obese rats treated with probiotics containing the probiotic strain Lactiplantibacillus Plantarum IMC 510 exhibited significantly lower weight and food intake than untreated obese rats.

Oral administration of probiotics has been proposed as a viable way to modulate/modify the gut ecosystem to promote weight reduction; however, the mechanisms by which probiotic supplementation may affect the gut microbiota of obese individuals are largely unknown. In addition, byproducts of the bacterial fermentation process may also reduce appetite and increase feelings of satiety, and through modulation of bile acid metabolism, the microbiota may reduce diet-induced obesity through increased energy expenditure. In addition, gut bacteria can manipulate an individual's taste and food preferences.

Over the past 25 years, more than 120 drugs have been studied for the treatment of obesity, but only very few have been approved and maintained on the market. Although exercise and diet are the first lines of intervention in correcting overweight, obesity and related metabolic diseases, because they are measures that must be adopted and followed for a long period of time, often experience failure or poor outcomes. Currently there is an increased interest in alternative and effective short term non-pharmacological approaches to weight control that involve the use of natural active ingredients. The use of specific probiotics could represent the future weapon to fight obesity through the modulation of the intestinal microbiota, which is becoming more and more important as a critical point both for the appearance of many diseases (if altered) and for the possibility of curing them by intervening to restore the intestinal flora.

Objectives of the study

The present clinical study is directed to the evaluation of the efficacy of a probiotic formulation containing the probiotic strain Lactiplantibacillus Plantarum IMC 510 in inducing and supporting weight loss and reduction of body circumferences in overweight or obese subjects through the regularization of appetite with consequent reduction of food intake.

Primary Objectives:

To evaluate weight reduction in obese and/or overweight subjects after 3 months of treatment with probiotic or placebo.

Secondary Objectives:

Collection of blood and fecal samples at recruitment, after 3 months of treatment (probiotic or placebo), and after a 1-month final wash out.
Measurement of BMI, body circumferences, body composition such as fat mass, lean mass, after 3 months of probiotic or placebo treatment, and after 1 month of wash out
Evaluation of general well-being, eating habits and any gastrointestinal symptoms
Comparison of hematological and biochemical parameters related to obesity at baseline, after 3 months of probiotic or placebo intervention, and after 1 month of washout
Analysis of the composition of the intestinal microbiota and the production of short-chain fatty acids (SCFA) and bile acids (FBA).

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized double-blind parallel controlled trialRandomized double-blind parallel controlled trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

By keeping both the experimenters and the participants blind, bias is less likely to influence the results of the experiment.

Primary Purpose:

Treatment

Official Title:

Novel Strategies for Obesity Prevention and Management With the Probiotic Lactiplantibacillus Plantarum IMC 510 (PRO-Weight-Control Study)

Actual Study Start Date :

Jan 7, 2022

Actual Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Probiotic Probiotic food supplement produced by SYNBIOTEC S.r.l.	Dietary Supplement: Probiotic Probiotic food supplement produced by SYNBIOTEC S.r.l. Each capsule of SYNBIO®slim contains the probiotic strain Lactiplantibacillus Plantarum IMC 510 at a concentration of 15 billion live cells (CFU/capsule). The assumption is of n°1 capsule/day, preferably at breakfast, for 3 months. The capsules can be opened and their content can be dispersed in a cold liquid or at intake temperature or in semi-solid food. Always store in original container or in a clean covered container, out of the reach of children. When stored in a dry, clean environment, out of direct sunlight, the product has a shelf-life of at least 24 months. Samples of probiotic supplement in closed and sealed boxes will be provided to subjects participating at the beginning of the study, in quantities sufficient for the entire duration of the study (90 capsules for 3 months).
Placebo Comparator: Placebo Placebo food supplement.	Dietary Supplement: Placebo N°1 capsule/day of placebo food supplement (i.e., capsules without added probiotics), with the same intake modalities as probiotic.

Arm

Intervention/Treatment

Experimental: Probiotic

Probiotic food supplement produced by SYNBIOTEC S.r.l.

Dietary Supplement: Probiotic

Probiotic food supplement produced by SYNBIOTEC S.r.l. Each capsule of SYNBIO®slim contains the probiotic strain Lactiplantibacillus Plantarum IMC 510 at a concentration of 15 billion live cells (CFU/capsule). The assumption is of n°1 capsule/day, preferably at breakfast, for 3 months. The capsules can be opened and their content can be dispersed in a cold liquid or at intake temperature or in semi-solid food. Always store in original container or in a clean covered container, out of the reach of children. When stored in a dry, clean environment, out of direct sunlight, the product has a shelf-life of at least 24 months. Samples of probiotic supplement in closed and sealed boxes will be provided to subjects participating at the beginning of the study, in quantities sufficient for the entire duration of the study (90 capsules for 3 months).

Placebo Comparator: Placebo

Placebo food supplement.

Dietary Supplement: Placebo

N°1 capsule/day of placebo food supplement (i.e., capsules without added probiotics), with the same intake modalities as probiotic.

Outcome Measures

Primary Outcome Measures

Body weight [2 months]
Changes of body weight from baseline assessed through a balance

Secondary Outcome Measures

Fat mass [2 months]
Changes of fat mass from baseline assessed through a bioelectrical impedance analysis device (BIA Akern, 101 Sport Edition).
Fat-free mass [2 months]
Changes of fat-free mass from baseline assessed through a bioelectrical impedance analysis device (BIA Akern, 101 Sport Edition).
Total body water [2 months]
Changes of total body water from baseline assessed through a bioelectrical impedance analysis device (BIA Akern, 101 Sport Edition).
White blood cells [2 months]
Changes of white blood cells from baseline assessed to standard laboratory procedures.
Red blood cells [2 months]
Changes of red blood cells from baseline assessed to standard laboratory procedures.
Hemoglobin [2 months]
Changes of hemoglobin from baseline assessed to standard laboratory procedures.
Glucose [2 months]
Changes of glucose from baseline assessed to standard laboratory procedures.
Urea [2 months]
Changes of urea from baseline assessed to standard laboratory procedures.
Creatinine [2 months]
Changes of creatinine from baseline assessed to standard laboratory procedures.
Sodium [2 months]
Changes of sodium from baseline assessed to standard laboratory procedures.
Potassium [2 months]
Changes of potassium from baseline assessed to standard laboratory procedures.
Calcium [2 months]
Changes of calcium from baseline assessed to standard laboratory procedures.
Magnesium [2 months]
Changes of magnesium from baseline assessed to standard laboratory procedures.
AST [2 months]
Changes of AST from baseline assessed to standard laboratory procedures.
ALT [2 months]
Changes of ALT from baseline assessed to standard laboratory procedures.
Triglycerides [2 months]
Changes of triglycerides from baseline assessed to standard laboratory procedures.
Total cholesterol [2 months]
Changes of total cholesterol from baseline assessed to standard laboratory procedures.
HDL-cholesterol [2 months]
Changes of HDL-cholesterol from baseline assessed to standard laboratory procedures.
LDL-cholesterol [2 months]
Changes of LDL-cholesterol from baseline assessed to standard laboratory procedures.
Uric Acid [2 months]
Changes of uric acid from baseline assessed to standard laboratory procedures.
eGFR [2 months]
Changes of eGFR from baseline assessed to standard laboratory procedures.
Gastrointestinal and systemic symptoms [2 months]
Changes of gastrointestinal and systemic symptoms from baseline assessed through a modified form of the Global Assessment of Improvement Scale (GAI), with a total score ranging from 0 to 56, with higher scores meaning an improvement of the symptoms and the Symptom Severity Scale (SSS), with a total score ranging from 0 to 500, with higher scores meaning more severe symptoms.
Gut microbiota [2 months]
Changes of gut microbiota from baseline assessed by Illumina MiSeq platform.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women 18-65 years of age
Obesity (BMI >30 kg/m2, class I, II, III) and overweight (BMI 25-29.9 kg/m2)
Willingness to cooperate during the study and ability to follow guidelines
Willingness to complete questionnaires and diaries associated with the study and to complete all clinical visits
Willingness to discontinue functional foods and dietary supplements with probiotics, laxatives and body weight control substances
Ability to provide informed consent

Exclusion Criteria:

Continued use of probiotics in the two months prior to treatment
Use of other treatments (medications or nutritional programs) that affect body weight, food intake and/or energy expenditure
Postmenopausal women
Pregnant or lactating
Enrolled in another obesity treatment program