FMT and Fiber in Patients With Metabolic Syndrome
Condition: Obesity; Metabolic Syndrome
MeSH terms: Obesity; Metabolic Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This study is looking at the safety and effectiveness of stool transplant, also known as
      Fecal Microbiota Transplantation (FMT) and prebiotic supplementation in the management of
      metabolic syndrome.

      Metabolic syndrome is a common progressive medical condition that is linked to obesity,
      diabetes, and heart disease. Obesity and metabolic syndrome are associated with abnormalities
      in gut flora which lead to chronic inflammation. This chronic inflammation is thought to
      worsen the insulin resistance and heart disease seen with metabolic syndrome. Current
      treatment strategies have shown limited effect, are expensive, and have side effects with
      long-term use.

      FMT is a one-time treatment that has been shown to replace the abnormal gut flora and improve
      metabolic disease by increasing anti-inflammatory short chain fatty acid (SCFA) production.
      However, the effects from FMT are not permanent. Prebiotic supplementation is one strategy
      that may help to extend the benefits of FMT by helping sustain high SCFA levels. At this
      point, it is not known how FMT and prebiotics work together to affect SCFA levels in
      participants with metabolic syndrome.

      This study will look at this interaction and answer if prebiotic therapy is effective in
      prolonging the benefits of FMT in participants with metabolic syndrome.
    

Detailed description: 
      3.0 Design This is an exploratory four-arm, parallel design, randomized placebo-controlled
      intervention study in obese individuals with metabolic syndrome to evaluate whether FMT from
      lean donors combined with supplementation with prebiotic fiber will have a clinically
      significant effect on metabolic parameters. The study includes a 2-week screening/baseline
      period followed by a single FMT and a 6 week study period in which prebiotic fiber or placebo
      will be added in powdered form to the subject's normal diet for the duration of the trial
      (Appendix 1). A follow-up visit at 12 weeks will be done to determine if beneficial effects
      are maintained in the absence of ongoing fiber intake. A parallel arm design was chosen to
      avoid cross-over effects.

      The four groups are:

        1. Control (Placebo FMT and cellulose)

        2. FMT only (FMT followed by cellulose)

        3. Prebiotic only (Placebo FMT and prebiotic fiber)

        4. FMT + prebiotic fiber Schedule and Procedures: Subjects will attend a total of 5 clinic
           appointments throughout the study for anthropometric and blood pressure measurements,
           dietary intake, hunger and satiety, and quality of life assessment using questionnaires,
           and for collection of blood and fecal samples (Appendix 2). The intervention will be
           stopped at 6 weeks. A final follow-up visit will occur at 12 weeks for anthropometric
           and blood pressure measurements, and collection of blood and stool samples.

      3.1 Randomization Subjects will be randomized to one of 4 groups via computer-generated
      numbers and stratified by gender. Individuals will be blinded as to their group allocation to
      reduce bias. Randomization concealment will be protected by several levels of security,
      including our secure website, password protection by only those authorized to randomize and a
      variable blocked randomization.

      3.2 Maintenance

      Randomized codes will be maintained in REDCAP. Codes will be broken at the end of the trial.

      3.3 Trial Treatment

      Fecal microbiome transplant (FMT): 50grams of FMT from a single, universal donor will be
      administered in 20-30 capsules taken by mouth. These capsules will be frozen at -700C until
      date of administration on day 1 of the trial. The FMT will be given after individuals have
      fasted overnight and completes a bowel preparation using Pico-Salax®, a routine colonoscopy
      preparation. The study will use only one donor to reduce variability in donor profiles unless
      this donor becomes unavailable at which point backup donors will be available. Placebo FMT
      will consist of cellulose pills.

      Fiber Supplementation:

      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 gm by mouth daily
           from day 4 until trial completion.

      The product will be supplied to patients on a weekly basis in pre-weighed foil packets.

      Placebo: Placebo will consist of cellulose powder (Microcrystalline cellulose:Blanver) in
      identical foil packets.

      3.4 Duration

      The study duration is 12 weeks. Subjects will be seen in the clinic at recruitment, and then
      at 2 and 6 weeks following FMT. Intervention will be from 1-6 weeks. A final follow-up visit
      will occur at 12 weeks (Appendix 1)
    

Intervention name(s): Fecal Microbial Transplant; Fiber; Cellulose
Intervention type(s): Combination Product; Dietary Supplement; Dietary Supplement
Intervention description(s): Fecal microbiome transplant (FMT): 50grams of FMT from a single, universal donor will be administered in 20-30 capsules taken by mouth.; A combination of soluble corn fiber (PROMITOR®: Tate&Lyle), Resistant Wheat Starch 4 (Fibersym®: MGP Ingredients), and Acacia Gum (Pre-Hydrated Gum Arabic: TIC GUMS) for a total of 6 weeks (men 33g/day; women 27g/day); Placebo will consist of cellulose powder (Microcrystalline cellulose:Blanver) in foil packets.
Other intervention name(s): FMT
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Fecal microbial transplant; obesity; metabolic syndrome