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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05358301
• Other study ID #: PRO-Weight-Control
• Status: Completed
• Phase: N/A
• Start date: January 7, 2022
• Est. completion date: October 31, 2022

Study information

• Verified date: February 2024
• Source: Azienda Ospedaliero-Universitaria Careggi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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:

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

Secondary Objectives:

1. Collection of blood and fecal samples at recruitment, after 3 months of treatment (probiotic or placebo), and after a 1-month final wash out.

2. 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

3. Evaluation of general well-being, eating habits and any gastrointestinal symptoms

4. 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

5. Analysis of the composition of the intestinal microbiota and the production of short-chain fatty acids (SCFA) and bile acids (FBA).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 31, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

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

Locations

Country	Name	City	State
Italy	Unit of Clinical Nutrition, University Hospital of Careggi	Florence

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria Careggi

Country where clinical trial is conducted

Italy, 

References & Publications (10)

Albanese D, De Filippo C, Cavalieri D, Donati C. Explaining diversity in metagenomic datasets by phylogenetic-based feature weighting. PLoS Comput Biol. 2015 Mar 27;11(3):e1004186. doi: 10.1371/journal.pcbi.1004186. eCollection 2015 Mar. — View Citation

Borgeraas H, Johnson LK, Skattebu J, Hertel JK, Hjelmesaeth J. Effects of probiotics on body weight, body mass index, fat mass and fat percentage in subjects with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2018 Feb;19(2):219-232. doi: 10.1111/obr.12626. Epub 2017 Oct 18. — View Citation

Chung HJ, Yu JG, Lee IA, Liu MJ, Shen YF, Sharma SP, Jamal MA, Yoo JH, Kim HJ, Hong ST. Intestinal removal of free fatty acids from hosts by Lactobacilli for the treatment of obesity. FEBS Open Bio. 2016 Jan 18;6(1):64-76. doi: 10.1002/2211-5463.12024. eCollection 2016 Jan. — View Citation

Dinan TG, Cryan JF. Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol Motil. 2013 Sep;25(9):713-9. doi: 10.1111/nmo.12198. — View Citation

Gomes AC, de Sousa RG, Botelho PB, Gomes TL, Prada PO, Mota JF. The additional effects of a probiotic mix on abdominal adiposity and antioxidant Status: A double-blind, randomized trial. Obesity (Silver Spring). 2017 Jan;25(1):30-38. doi: 10.1002/oby.21671. — View Citation

John GK, Wang L, Nanavati J, Twose C, Singh R, Mullin G. Dietary Alteration of the Gut Microbiome and Its Impact on Weight and Fat Mass: A Systematic Review and Meta-Analysis. Genes (Basel). 2018 Mar 16;9(3):167. doi: 10.3390/genes9030167. — View Citation

Sanchez M, Darimont C, Panahi S, Drapeau V, Marette A, Taylor VH, Dore J, Tremblay A. Effects of a Diet-Based Weight-Reducing Program with Probiotic Supplementation on Satiety Efficiency, Eating Behaviour Traits, and Psychosocial Behaviours in Obese Individuals. Nutrients. 2017 Mar 15;9(3):284. doi: 10.3390/nu9030284. — View Citation

Sanders ME. Probiotics and microbiota composition. BMC Med. 2016 Jun 2;14(1):82. doi: 10.1186/s12916-016-0629-z. — View Citation

Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011 Jun 24;12(6):R60. doi: 10.1186/gb-2011-12-6-r60. — View Citation

Verdenelli MC, Ghelfi F, Silvi S, Orpianesi C, Cecchini C, Cresci A. Probiotic properties of Lactobacillus rhamnosus and Lactobacillus paracasei isolated from human faeces. Eur J Nutr. 2009 Sep;48(6):355-63. doi: 10.1007/s00394-009-0021-2. Epub 2009 Apr 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body weight	Changes of body weight from baseline assessed through a balance	2 months
Secondary	Fat mass	Changes of fat mass from baseline assessed through a bioelectrical impedance analysis device (BIA Akern, 101 Sport Edition).	2 months
Secondary	Fat-free mass	Changes of fat-free mass from baseline assessed through a bioelectrical impedance analysis device (BIA Akern, 101 Sport Edition).	2 months
Secondary	Total body water	Changes of total body water from baseline assessed through a bioelectrical impedance analysis device (BIA Akern, 101 Sport Edition).	2 months
Secondary	White blood cells	Changes of white blood cells from baseline assessed to standard laboratory procedures.	2 months
Secondary	Red blood cells	Changes of red blood cells from baseline assessed to standard laboratory procedures.	2 months
Secondary	Hemoglobin	Changes of hemoglobin from baseline assessed to standard laboratory procedures.	2 months
Secondary	Glucose	Changes of glucose from baseline assessed to standard laboratory procedures.	2 months
Secondary	Urea	Changes of urea from baseline assessed to standard laboratory procedures.	2 months
Secondary	Creatinine	Changes of creatinine from baseline assessed to standard laboratory procedures.	2 months
Secondary	Sodium	Changes of sodium from baseline assessed to standard laboratory procedures.	2 months
Secondary	Potassium	Changes of potassium from baseline assessed to standard laboratory procedures.	2 months
Secondary	Calcium	Changes of calcium from baseline assessed to standard laboratory procedures.	2 months
Secondary	Magnesium	Changes of magnesium from baseline assessed to standard laboratory procedures.	2 months
Secondary	AST	Changes of AST from baseline assessed to standard laboratory procedures.	2 months
Secondary	ALT	Changes of ALT from baseline assessed to standard laboratory procedures.	2 months
Secondary	Triglycerides	Changes of triglycerides from baseline assessed to standard laboratory procedures.	2 months
Secondary	Total cholesterol	Changes of total cholesterol from baseline assessed to standard laboratory procedures.	2 months
Secondary	HDL-cholesterol	Changes of HDL-cholesterol from baseline assessed to standard laboratory procedures.	2 months
Secondary	LDL-cholesterol	Changes of LDL-cholesterol from baseline assessed to standard laboratory procedures.	2 months
Secondary	Uric Acid	Changes of uric acid from baseline assessed to standard laboratory procedures.	2 months
Secondary	eGFR	Changes of eGFR from baseline assessed to standard laboratory procedures.	2 months
Secondary	Gastrointestinal and systemic symptoms	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.	2 months
Secondary	Gut microbiota	Changes of gut microbiota from baseline assessed by Illumina MiSeq platform.	2 months