Fecal Microbial Transplantation and Fiber Supplementation in Participants With Obesity and Metabolic Syndrome.
Condition: Obesity; Metabolic Syndrome
MeSH terms: Obesity; Metabolic Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      Obesity is increasing in western society at a rapid rate and is associated with metabolic and
      cardiovascular disease. Although genetics, improper diet, and sedentary lifestyle are known
      to be factors that can cause obesity, there is a new idea that certain gut microbes may also
      be involved. Patients who are obese tend to have different kinds of gut microbes compared
      with lean healthy individuals. Previous studies have shown that changing the gut microbes of
      obese individuals by doing a fecal transplant (FMT) using gut microbes from a lean individual
      improves insulin resistance. However, the effects were not maintained. In addition, research
      has highlighted a necessary role for dietary fiber in the maintenance of microbes required
      for human health and also that increasing dietary fiber can reduce inflammation that is
      associated with insulin resistance. This project builds on the findings that gut microbes can
      be modulated by both FMT and dietary fiber supplementation and will examine if combining
      these two treatments can increase the effectiveness of these treatments.

      The objective of this study is to use fecal microbial transplant to change the gut microbes
      of obese individuals to those seen in lean individuals and then to use fiber supplements to
      help maintain the beneficial effects. In this study, overweight individuals who have
      metabolic syndrome will receive a fecal transplant using a pill form and then consume a
      variety of fiber supplements for 6 weeks. Effects on metabolic parameters, quality of life,
      weight, and dietary intake will be followed. Microbial composition will be measured in stool
      samples.
    

Detailed description: 
      Phase: This is a phase II clinical trial.

      Methodology: This is an exploratory, four-arm, parallel design, randomized placebo-controlled
      intervention study.

      Study Duration: 12 weeks Study Center(s): This is a single center trial at the University of
      Alberta

      Objectives:The objective of this study is to determine if fecal microbial transplantation
      (FMT) combined with supplementation with a combined fiber supplement of resistant starch type
      4, acacia gum, and soluble corn fiber has a clinically significant effect on metabolic
      outcomes in obese subjects with metabolic syndrome

      Primary Outcome: Changes in insulin sensitivity between the time of screening and 6 weeks
      following treatment.

      Secondary Outcomes:

        -  Changes in Body weight and anthropometric parameters between baseline and week 6.

        -  Changes in HbA1C, fasting glucose, glucose tolerance test between baseline and week 6

        -  Changes in fasting lipid profile between baseline and week 6

        -  Changes in blood pressure between baseline and week 6

        -  Quality of life and satiety between baseline and week 6

        -  Changes in serum levels of leptin, adiponectin, ghrelin, CRP, TNF-α, IL-6, LPS,
           LPS-binding protein and zonulin between baseline and week 6

        -  Changes in stool microbiota composition between baseline and week 6

        -  Changes in stool short chain fatty acid composition between baseline and week 6

      Number of Subjects: 68

      Diagnosis and Main Inclusion Criteria

      Primary Diagnosis:

      • BMI > 30

      Key Inclusion Criteria:

        -  Age 18-64 years at screening

        -  Total body weight fluctuation over the last 6 months <10%

        -  Fasting plasma glucose > 5.6 mmol/L OR HgbA1c ≥6.5% (with or without taking an oral
           antidiabetic medication)

        -  At least one of the following:

             -  Fasting triglyceride ≥1.7 mmol/L (with or without taking a statin or fibrate)

             -  HDL cholesterol <1.03 mmol/L in males or <1.29 mmol/L in females (with or without
                taking a statin or fibrate)

             -  Known diagnosis of hypertension OR systolic blood pressure ≥130 or diastolic blood
                pressure ≥85 mmHg (with or without taking at least one antihypertensive agent).

      Study Product, Dose, Route, Regimen FMT:

        -  50 gm of screened and encapsulated single donor stool (approximately 20-30 capsules)
           taken by mouth on day 1 of the trial after having fasted overnight and completed a bowel
           prep with Pico-Salax®.

        -  Placebo pills will contain microcrystalline cellulose

      Soluble corn fiber (PROMITOR®: Tate&Lyle)

        -  Women: 4.5 gm of PROMITOR by mouth days 1-3 increased to 9 gm daily from day 4 until
           trial completion.

        -  Men: 5.5 gm of PROMITOR by mouth days 1-3 increased to 11 gm by mouth daily from day 4
           until trial completion.

      Resistant Wheat Starch 4 (Fibersym®: MGP Ingredients):

        -  Women: 4.5 gm of powdered RS4 by mouth days 1-3 increased to 9 gm by mouth daily from
           day 4 until trial completion.

        -  Men: 5.5gm of powdered RS4 by mouth days 1-3 increased to 11 gm by mouth daily from day
           4 until trial completion.

      Acacia Gum (Pre-Hydrated Gum Arabic: TIC GUMS):

        -  Women: 4.5 gm of powdered acacia gum by mouth days 1-3 increased to 9 gm by mouth daily
           from day 4 until trial completion.

        -  Men: 5.5gm of powdered acacia gum by mouth days 1-3 increased to 11 gr by mouth daily
           from day 4 until trial completion.

      Duration of administration:

      FMT: Single dose of 50gm donor stool or placebo (microcrystalline cellulose) on day 1.

      Fiber: Daily administration until completion at week 6

      Reference therapy Both FMT and Fiber will be placebo matched as reference therapy.

      Statistical Methodology: Study groups with by analyzed by pair-wise comparison with
      evaluation of means between and across groups using paired or unpaired t-tests for continuous
      outcomes and chi-squared tests for dichotomous ones. Multivariable predictors of change in
      relevant outcomes will be identified using appropriately constructed and calibrated linear
      regression models for continuous outcomes or logistic regression models for dichotomous ones.
    

Intervention name(s): FMT; Placebo FMT; Prebiotic Fiber; Cellulose
Intervention type(s): Biological; Biological; Dietary Supplement; Dietary Supplement
Intervention description(s): fecal microbial transplantation (FMT); Placebo fecal microbial transplantation (FMT); combined fiber supplement of resistant starch type 4, acacia gum, and soluble corn fiber; Cellulose
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment