Clinical trial NCT01250106: Probiotics as a Novel Approach to Modulate Gut Hormone Secretion and Risk Factors of Type 2 Diabetes and Complications
Official title: Phase I Study of Probiotics as a Novel Approach to Modulate Gut Hormone Secretion and Risk Factors of Type 2 Diabetes and Complications
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Obesity
Type 2 Diabetes
Keywords: probiotics
prevention
dietary intervention
insulin resistance
obesity
type 2 diabetes
Lead sponsor: German Diabetes Center
Sponsor class: OTHER
Collaborators: name: Heinrich-Heine University, Duesseldorf
First posted: 2010-11-30
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The investigators aim to test the hypothesis that Lactobacillus Reuteri-enriched microbiota improves insulin sensitivity and glucose tolerance in obese healthy and obese type 2 diabetes patients by improving gut hormone secretion and compare these findings to healthy lean subjects.

Detailed description: Prediabetes and diabetes are accompanied by insufficient gut hormone release, insulin resistance, insufficient insulin secretory capacity and low grade systemic inflammation. Results of recent animal experiments suggest that ingestion of probiotics not only influences gut microbiota composition and intestinal permeability but also secretion of GLP-2 as well as insulin resistance, components of metabolic syndrome and diabetes development. GLP-2 secretion has been suggested to be a key mediator of probiotic effects mediating decreased intestine permeability through binding to intestinal GLP2 receptor in animal studies. Insulinotropic GLP-1, which is reduced in patients with type 2 diabetes, has also been described to be influenced by gut microbiota composition. We aim to test the hypothesis that Lactobacillus Reuteri-enriched microbiota improves insulin sensitivity and glucose tolerance in obese healthy and obese type 2 diabetes patients by improving gut hormone secretion. In a prospective, double-blinded, placebo controlled randomized 10 weeks trial we aim to investigate metabolic and immunological changes related to modified gut microbiota by analysing (1) gut hormone secretion, (2) insulin sensitivity and glucose tolerance, and (3) systemic LPS concentrations and immune status.

Eligibility criteria: Inclusion Criteria:

* Obese subjects: age 40 - 65 years, obesity (BMI 30-45 kg/m2), non-smoking, absence of gastrointestinal disease, willingness to abstain from intake of fermented milk products over a study period of 8 weeks.
* Healthy control subjects: non-obese (BMI 19-25 kg/m2), non-diabetic subjects, matched for age and sex, non-smoking, absence of gastrointestinal disease, willingness to abstain from intake of fermented milk products over a study period of 8 weeks.

Exclusion Criteria:

* pregnancy, cancer, chronic diseases, antibiotic therapy, competitive athletes.

Primary outcomes:
measure: Insulin resistance
timeFrame: 8 weeks
Secondary outcomes:
measure: gut hormones (GLP-1, GLP-2, GIP)
timeFrame: 8 and 10 weeks
measure: insulin secretion
timeFrame: 8 and 10 weeks
measure: measurement of cytokines to define the immune status
timeFrame: 8 and 10 weeks
measure: body weight
timeFrame: 8 and 10 weeks
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: German Diabetes Center
state: Duesseldorf
Study officials:
affiliation: German Diabetes Center, Duesseldorf
name: Nanette C Schloot, Priv.-Doz. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Simon MC, Strassburger K, Nowotny B, Kolb H, Nowotny P, Burkart V, Zivehe F, Hwang JH, Stehle P, Pacini G, Hartmann B, Holst JJ, MacKenzie C, Bindels LB, Martinez I, Walter J, Henrich B, Schloot NC, Roden M. Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept. Diabetes Care. 2015 Oct;38(10):1827-34. doi: 10.2337/dc14-2690. Epub 2015 Jun 17.