Probiotics and the Gut Microbiome in Obese Hispanic Youth

Adiposity Clinical Trial

Official title:

Probiotics and the Gut Microbiome in Obese Hispanic Youth

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03115385
• Other study ID #: HS-14-00683
• Status: Terminated
• Phase: N/A
• First received: March 29, 2017
• Last updated: April 10, 2017
• Start date: May 30, 2015
• Est. completion date: April 11, 2016

Study information

• Verified date: April 2017
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will recruit 40 obese Hispanic youth (12 - 18 years of age who are greater than or equal to Tanner stage 4) from hospitals, clinics, and community centers. Participants will be randomly assigned to 16 weeks of probiotics (3 packets/day of VSL#3) or matched placebo. The purpose of this study is to demonstrate through a proof-of-concept trial that probiotics have the potential to alter the gut microbiome and gut hormones.

Description:

Recent studies suggest that probiotic supplementation has the potential to restore gut microbiota homeostasis and reduce fatty liver. No studies have examined the effects of probiotic supplementation on the gut microbiome in obese Hispanic youth who are increased risk of type 2 diabetes and fatty liver. Therefore, the investigator proposes a double-blind randomized trial of probiotic supplementation in obese Hispanic youth in order to determine if probiotic supplementation results in alterations to the gut micro biome. The purpose of this study is to demonstrate through a proof-of-concept trial that probiotics have the potential to alter the gut microbiome and gut hormones. As a secondary aim the investigator will examine wether any changes in the gut microbiome are related to changes in liver fat, fibrosis, glycemia, or body weight. The study team will recruit 40 obese Hispanic youth (12 - 18 years of age who are greater than or equal to Tanner stage 4) from hospitals, clinics, and community centers. The studies primary outcome is alterations in the composition of the gut microbiome which will be examined through fecal and blood bacterial profiling (16S DNA targeted metagenomics), markers of gut permeability/bacterial translocation, and gut derived hormones involved with appetite regulation (GLP-1, peptide YY, ghrelin). Secondary outcomes include liver fat and liver fibrosis (MR elastography), total body fat (DEXA), visceral fat (MRI). Participants will be randomly assigned to 16 weeks of probiotics (3 packets/day of VSL#3) or matched placebo. The main effects of the intervention will be evaluated in a general linear model, with change in outcomes as the dependent variable and active intervention group as the independent variable. Covariates will include sex, BMI percentile, the baseline value of the outcome variable, as well as baseline factors found to differ among groups. Post hoc pairwise comparisons of the two groups will adjust for multiple comparisons using a Tukey correction.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: April 11, 2016
• Est. primary completion date: April 11, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

Inclusion Criteria:

Inclusion Criteria:

• Obese (BMI percentile =95th for age and gender)

• Hispanic males and females who are 12-18 years of age and are =Tanner Stage 4.

Exclusion Criteria:

Participants will be excluded from the study if any of the following apply:

1. diagnosis of any disease that is known to influence insulin action and secretion (including type 1 and 2 diabetes);

2. current or past involvement in any weight loss, exercise, or sports program in the six months prior to participation

3. use of medication known to influence body composition or fat distribution (e.g. Cushing syndrome), insulin resistance, gut function, or lipid profiles;

4. history of renal / liver disease or any disease affecting liver fibrosis and steatosis;

5. diagnosis/current treatment for celiac, inflammatory bowel disease, Crohn's disease or other major GI issues;

6. those who are immune compromised;

7. pregnancy;

8. current smoking (more than 1 cigarette in the past week), >200 cigarettes in lifetime, or use of other recreational drugs;

9. alcohol consumption;

10. other siblings in the study;

11. physician diagnosis of major illness or eating disorder;

12. physical/cognitive handicaps preventing participation;

13. and recent antibiotic treatment (within the previous 30 days).

Related Conditions & MeSH terms

• Adiposity
• Obesity, Abdominal

Intervention

Dietary Supplement:
• VSL#3
VSL#3 will provide active packets. Subjects will take 2 to 3 packets per day with for 16 weeks. The study team will supply each participant with all necessary packets on a weekly or bi-weekly basis within 1-2 weeks after their first visit. VSL#3 probiotic is provided in powder form and needs to be mixed with cold, non-fizzy liquid for consumption. For this reason, the study team will also provide participants with zero calorie sugar fee beverages to mix their packet with (e.g., vitamin water zero with stevia).
• Placebo
A matched placebo to VSL#3 will be provided. The placebo will be identical to the active VSL#3 probiotic in aspects such as packaging, color, taste, texture, shape, and odor. The placebo will not contain active ingredients. The study team will supply each participant with all necessary packets on a weekly or bi-weekly basis within 1-2 weeks after their first visit. The placebo is provided in powder form and needs to be mixed with liquid for consumption. For this reason, the study team will also provide participants with zero calorie sugar fee beverages to mix their packet with (e.g., vitamin water zero).

Locations

Country	Name	City	State
United States	University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

References & Publications (8)

Alisi A, Bedogni G, Baviera G, Giorgio V, Porro E, Paris C, Giammaria P, Reali L, Anania F, Nobili V. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2014 Jun;39(11): — View Citation

Chang B, Sang L, Wang Y, Tong J, Zhang D, Wang B. The protective effect of VSL#3 on intestinal permeability in a rat model of alcoholic intestinal injury. BMC Gastroenterol. 2013 Oct 20;13:151. doi: 10.1186/1471-230X-13-151. — View Citation

Delzenne NM, Neyrinck AM, Bäckhed F, Cani PD. Targeting gut microbiota in obesity: effects of prebiotics and probiotics. Nat Rev Endocrinol. 2011 Aug 9;7(11):639-46. doi: 10.1038/nrendo.2011.126. Review. — View Citation

Eslamparast T, Eghtesad S, Hekmatdoost A, Poustchi H. Probiotics and Nonalcoholic Fatty liver Disease. Middle East J Dig Dis. 2013 Jul;5(3):129-36. Review. — View Citation

Kootte RS, Vrieze A, Holleman F, Dallinga-Thie GM, Zoetendal EG, de Vos WM, Groen AK, Hoekstra JB, Stroes ES, Nieuwdorp M. The therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus. Diabetes Obes Metab. 2012 Feb;14(2 — View Citation

Rajkumar H, Mahmood N, Kumar M, Varikuti SR, Challa HR, Myakala SP. Effect of probiotic (VSL#3) and omega-3 on lipid profile, insulin sensitivity, inflammatory markers, and gut colonization in overweight adults: a randomized, controlled trial. Mediators I — View Citation

Wang J, Tang H, Zhang C, Zhao Y, Derrien M, Rocher E, van-Hylckama Vlieg JE, Strissel K, Zhao L, Obin M, Shen J. Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME J. 2015 Jan;9(1):1-15 — View Citation

Wong VW, Won GL, Chim AM, Chu WC, Yeung DK, Li KC, Chan HL. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann Hepatol. 2013 Mar-Apr;12(2):256-62. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in abundance of gut microbiome and gut hormones measured pre and post blood and stool sample collections.	To determine whether probiotic (VSL#3) supplementation affects gut microbiome and gut hormones involved with appetite regulation in obese young Hispanics.	16 weeks
Secondary	Interaction between gut microbiome and liver fat, fibrosis, obesity, and glycemia measured pre and post blood and stool sample collections and through Dxa and MRI scans..	To determine whether there are any relationships between changes in the gut microbiome and changes in liver fat, fibrosis, obesity, and glycemia after 16 weeks of probiotic supplementation.	16 weeks