Fecal Microbial Transplantation and Fiber Supplementation in Participants With Obesity and Metabolic Syndrome.

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.

Inclusion criteria

• • Age ≥ 18 and < 65 years at the time of screening

• BMI > 30
• Total body weight fluctuation over the last 6 months less than 10%
• Fasting plasma glucose (FPG): 1) > 5.6 mmol/L OR Hemoglobin A1c ≥6.5% (with or without taking an oral antidiabetic medication).
• At least one of the following criterion:

• Fasting triglyceride ≥1.7 (TG) 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)
• Established diagnosis of hypertension OR SBP ≥130 or DBP ≥85 mmHg (with or without taking at least one antihypertensive agent).

Exclusion criteria

• • Systolic blood pressure ≥180 or diastolic blood pressure ≥110 mmHg at screening.

• Triglyceride ≥6 mmol/L.
• Acute infectious or inflammatory condition over the presiding 4 weeks.
• Current or recent use (Previous 6 months) of insulin for diabetes control.
• History of oropharyngeal or significant esophageal dysphagia, inflammatory bowel disease, colon cancer, or colonic polyps with high grade dysplasia.
• History of autoimmune conditions or chronic inflammatory condition, such as rheumatoid arthritis, chronic active hepatitis B or C, HIV, chronic pancreatitis, advanced NASH, or liver cirrhosis.
• Active malignancy.
• Active substance abuse or excessive EtOH (defined as >2 X 8oz drinks/d).