Clinical trial NCT02346669: Fecal Microbiota Transplantation for Diabetes Mellitus Type II in Obese Patients
Official title: Fecal Microbiota Transplantation for Diabetes Mellitus Type II in Obese Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Obesity
Keywords: Microbiota
Diabetes Mellitus, Type 2
Obesity
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2015-01-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The incidence of obesity has dramatically increased during the last three decades, leading to a significant increase of obesity-related morbidity, including type 2 diabetes mellitus (T2DM) that is characterized by resistance of target tissues to insulin action. T2DM obese patients may be treated by medications or by bariatric surgery. Both alternatives have limitations due to incomplete resolution of the diseases, high cost or potential procedural related morbidity. An increasing body of evidence points to a role of the enteric microbiota in the pathogenesis of obesity-related insulin resistance. In addition to that, the gut microbiota is directly affected by the diet composition. Studies in T2DM mice carrying human gut germs, demonstrated special interactions between the gut microbiota and the host, creating a typical microbiota composition which changes significantly following diet change from a western diet, rich with sugar, to a vegetarian diet rich with fibers. This rapid alternations in the microbiota composition has also shown in humans, after changing from western to high fiber diet. A change in diet life style may lead to an improvement in T2DM symptoms such as decrease in visceral adipose tissue.

Detailed description: Study design:

30 Patients will undergo 2 FMT's from a lean donor and will be randomized into 3 types of diet groups:

1. low fat high fiber diet (20% fat)
2. no change in fat intake (sham diet)
3. high fat low fiber diet (40-45% fat)

The treating physicians and the patients will be blinded for the diet arm. Before and after FMT, patients will be assessed after an overnight fast (and before taking medications) for weight, anthropometric measures, questionnaires (dietary, general health, antibiotic and probiotic exposure, oral diabetes medication quantity, and other drug exposure), blood and stool.

The investigators hypothesize that fecal microbial transplantation from a lean donor to T2DM obese patients, with the combination of low fat high fiber diet, will alter the gut microbiota composition to decrease insulin resistance through microbiota dependent metabolic and immunologic effects.

Eligibility criteria: Inclusion Criteria:

* 30≤BMI
* A diagnosis of T2DM (≥3 months) and one of the following:

  1. Fasting glucose level≥126mg/dL and/ or
  2. A stable dose of anti-diabetic drugs for ≥2 weeks and/or
  3. HbA1C≥6.5
* Access to a smart phone supporting the research application for tracking food consumption.

Exclusion Criteria:

* participation in other clinical trial
* incapable of signing an informed consent
* pregnancy or breast feeding
* Antibiotic treatment within the prior 3 months or predicted antibiotic treatment
* insulin medications
* drugs or alcohol addiction
* immune mediated diseases
* type 1 diabetes and latent autoimmune diabetes of adults
* systemic disease
* ischemic heart disease
* probiotics consumption
* a new or unstable treatment with anti diabetic medications

Patients will also be excluded if:

* treated by systemic antibiotic during the study
* will not be compliant with the diet

Primary outcomes:
measure: 30% decrease in insulin resistance
timeFrame: 6 weeks after first FMT
measure: 40% decrease in insulin resistance compared to baseline
timeFrame: 12 weeks after second FMT
Secondary outcomes:
measure: Decreased use of diabetes medications
timeFrame: Week 6 and 12 post FMT
measure: Improvement in anthropometric measures and in metabolic indices
timeFrame: week 6 and 12 post FMT
measure: Maintenance of an improved insulin resistance
timeFrame: 28 weeks post FMT
measure: Maintenance of altered of enteric microbiota in the three diet groups
timeFrame: 6, 12, 28 weeks post FMT
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Department of Gastroentherology
Study officials:
affiliation: Tel Aviv Medical Center
name: Nitsan Maharshak, MD
role: PRINCIPAL_INVESTIGATOR
References: