Fecal Microbiota Transplantation for Diabetes Mellitus Type II in Obese Patients

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.

Study Overview

• Status: Unknown
• Conditions: Obesity; Diabetes Mellitus, Type 2
• Intervention / Treatment: Procedure: gastroscopy; Drug: Fecal Microbiota Transplantation; Other: high fat low fiber diet; Other: sham diet; Other: low fat high fiber diet

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nitsan Maharshak, MD; Phone Number: 972-3-6972488; Email: nitsanm@tlvmc.gov.il

Study Locations

• Israel
  • Tel Aviv, Israel, 64239
    • Recruiting
    • Department of Gastroentherology
    • Sub-Investigator: Eran Segal, Prof.
    • Principal Investigator: Nitsan Maharshak, MD
    • Contact: Nitsan Maharshak, MD; Phone Number: 972-3-6972488; Email: nitsanm@tlvmc.gov.il
    • Sub-Investigator: Zamir Halpern, Prof.
    • Sub-Investigator: Nethaniel Cohen, MD
    • Sub-Investigator: Meirav Ben-Yehoyada, PHD
    • Sub-Investigator: Iddo Bar Yishay, MD
    • Sub-Investigator: Ronnie Baruch, B.Sc Nut

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FMT from a lean donor+ high fat diet; Patients will undergo FMT (Fecal Microboita Transplantation) from a lean donor twice during study through a gastroscopy: at time 0; after 6 weeks Patient will start high fat low fiber diet 2 weeks before first FMT and continue on consuming the same diet 9 weeks after the first FMT. Patient will be followed up by a nutritionist through the the study.	Procedure: gastroscopy; as detailed in arm description; Drug: Fecal Microbiota Transplantation; as detailed in arm description; Other: high fat low fiber diet; as detailed in arm description
Sham Comparator: FMT from a lean donor+ sham diet; Patients will undergo FMT (Fecal Microboita Transplantation) from a lean donor twice during study through a gastroscopy: at time 0; after 6 weeks Patient will start sham diet (no change in fat/fiber consumption) 2 weeks before first FMT and continue on consuming the same diet 9 weeks after the first FMT. Patient will be followed up by a nutritionist through the the study.	Procedure: gastroscopy; as detailed in arm description; Drug: Fecal Microbiota Transplantation; as detailed in arm description; Other: sham diet; as detailed in arm description
Active Comparator: FMT from lean donor+ low fat diet; Patients will undergo FMT (Fecal Microboita Transplantation) from a lean donor twice during study through a gastroscopy: at time 0; after 6 weeks Patient will start low fat high fiber diet 2 weeks before first FMT and continue on consuming the same diet 9 weeks after the first FMT. Patient will be followed up by a nutritionist through the the study.	Procedure: gastroscopy; as detailed in arm description; Drug: Fecal Microbiota Transplantation; as detailed in arm description; Other: low fat high fiber diet; as detailed in arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30% decrease in insulin resistance	Lean donor FMT will result in 30% decrease in insulin resistance that will be further enhanced after a second FMT. These will be meditated by an alteration of intestinal microbiota	6 weeks after first FMT
40% decrease in insulin resistance compared to baseline		12 weeks after second FMT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decreased use of diabetes medications		Week 6 and 12 post FMT
Improvement in anthropometric measures and in metabolic indices	At least 5% decrease in waist to hip ratio and in total body weight	week 6 and 12 post FMT
Maintenance of an improved insulin resistance	Insulin resistance at 28 weeks will be in the range (+5% to -5%) of the value achieved at week 12.	28 weeks post FMT
Maintenance of altered of enteric microbiota in the three diet groups		6, 12, 28 weeks post FMT

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: January 8, 2015
• First Submitted That Met QC Criteria: January 20, 2015
• First Posted (Estimate): January 27, 2015

Study Record Updates

• Last Update Posted (Estimate): June 9, 2016
• Last Update Submitted That Met QC Criteria: June 8, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Obesity; Microbiota; Diabetes Mellitus, Type 2
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: TASMC-14-NM-447-CTIL