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FMT and Fiber in Patients With Metabolic Syndrome (FMT)

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ClinicalTrials.gov Identifier: NCT03727321
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : May 2, 2019
Sponsor:
Collaborator:
The Weston A. Price Foundation
Information provided by (Responsible Party):
University of Alberta

Brief 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.


Condition or disease Intervention/treatment Phase
Obesity Metabolic Syndrome Combination Product: Fecal Microbial Transplant Dietary Supplement: Fiber Dietary Supplement: Cellulose Phase 2

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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)


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Fecal Microbial Transplantation and Fiber Supplementation in Subjects With Obesity and Metabolic Syndrome
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : March 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo: Placebo will consist of cellulose powder (Microcrystalline cellulose:Blanver) in foil packets.
Dietary Supplement: Cellulose
Placebo will consist of cellulose powder (Microcrystalline cellulose:Blanver) in foil packets.

Experimental: Fecal Microbial Transplant and cellulose
  1. Fecal Microbial Transplant - Fecal microbiome transplant (FMT): 50grams of FMT from a single, universal donor will be administered in 20-30 capsules taken by mouth.
  2. Cellulose x 6weeks
Combination Product: Fecal Microbial Transplant
Fecal microbiome transplant (FMT): 50grams of FMT from a single, universal donor will be administered in 20-30 capsules taken by mouth.
Other Name: FMT

Dietary Supplement: Cellulose
Placebo will consist of cellulose powder (Microcrystalline cellulose:Blanver) in foil packets.

Experimental: Fiber
Soluble corn fiber (PROMITOR®: Tate&Lyle), Resistant Wheat Starch 4 (Fibersym®: MGP Ingredients), Acacia Gum (Pre-Hydrated Gum Arabic: TIC GUMS).
Dietary Supplement: Fiber
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)

Experimental: Fecal Microbial Transplant and Fiber
  1. Fecal Microbial Transplant
  2. Soluble corn fiber (PROMITOR®: Tate&Lyle), Resistant Wheat Starch 4 (Fibersym®: MGP Ingredients), Acacia Gum (Pre-Hydrated Gum Arabic: TIC GUMS).
Combination Product: Fecal Microbial Transplant
Fecal microbiome transplant (FMT): 50grams of FMT from a single, universal donor will be administered in 20-30 capsules taken by mouth.
Other Name: FMT

Dietary Supplement: Fiber
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)




Primary Outcome Measures :
  1. Insulin Sensitivity Assessment [ Time Frame: 12 weeks ]
    The homeostasis Model Assessment-Insulin Resistance (HOMA-IR) is a mathematical model to predict the interaction between glucose and insulin dynamics across a range of glucose plasma levels assuming a feedback circuit between the liver and β-cells in the pancreas


Secondary Outcome Measures :
  1. Health-related quality of life (HRQL): EQ-5D Index [ Time Frame: 12 week ]
    Assessment of the current health related quality of life will be accomplished by conducting standardized interviews and by using the validated questionnaires EQ-5D Index. Participants will report perceived health outcomes using this validated survey, and rank overall perceived health from 0 (low)- 100 (high).

  2. Dietary Intake [ Time Frame: 12 week ]
    Dietary intake will be assessed for each clinic using MyFitnessPal.

  3. Inflammatory markers [ Time Frame: 12 week ]
    . Levels of leptin, ghrelin, adiponectin, TNFα, IL-6, LPS (lipopolysaccharide), LPS-binding protein and zonulin will be determined using currently accepted laboratory techniques.

  4. Stool Microbiome [ Time Frame: 12 weeks ]
    Stool microbiome will be analyzed for Operational Taxonomic Unit determination.

  5. Anthropometric Measurements [ Time Frame: 12 weeks ]
    BMI (kg/m2)

  6. Fasting lipid profile [ Time Frame: 12 weeks ]
    Changes in Fasting lipid profile between baseline and 6 and 12 weeks

  7. Glucose Tolerance Assessment [ Time Frame: 12 weeks ]
    The oral glucose tolerance test (OGTT) is a dynamic test that reflects the efficiency of the body to dispose of glucose after an oral load. It is commonly used in clinical scenarios to diagnose glucose intolerance and diabetes. [33] After overnight fast (> 8 h), blood samples for determination of glucose and insulin concentration will be taken at -5, 0, 30, 60, and 120 min following a standard oral glucose load.

  8. Hunger and Satiety Assessment [ Time Frame: 12 weeks ]
    Assessed via the standardized hunger and satiety questionnaire (categorical variables with no analog scale)

  9. Gastrointestinal tolerance [ Time Frame: 12 weeks ]
    Assessed via the standardized gastrointestinal tolerance questionnaire (categorical variables with no analog scale)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 > 5.6 mmol/L OR HgbA1c ≥5.5% OR patients receiving an antidiabetic medication
    • At least one of the following:

      • Fasting triglyceride ≥1.7 mmol/L OR receiving dyslipidemia medication
      • HDL cholesterol <1.03 mmol/L in males or <1.29 mmol/L in females OR receiving dyslipidemia medication
      • Known diagnosis of hypertension OR systolic blood pressure ≥130 or diastolic blood pressure ≥85 mmHg OR receiving antihypertension medication

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727321


Contacts
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Contact: Valentin Mocanu, MD 7809097109 vmocanu1987@gmail.com
Contact: Karen Madsen, PhD 7804925257 kmadsen@ualberta.ca

Locations
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Canada, Alberta
Royal Alexandra Hospital Recruiting
Edmonton, Alberta, Canada, T5H 3V9
Contact: Valentin Mocanu, MD    7809097109    vmocanu1987@gmail.com   
Contact: Karen Madsen, PhD    7804925257    kmadsen@ualberta.ca   
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Valentin Mocanu, MD    7809097109    vmocanu1987@gmail.com   
Contact: Karen Madsen, PhD    7804925257    kmadsen@ualberta.ca   
Principal Investigator: Karen Madsen, PhD         
Sub-Investigator: Valentin Mocanu, MD         
Sponsors and Collaborators
University of Alberta
The Weston A. Price Foundation
Investigators
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Principal Investigator: Karen Madsen, PhD University of Alberta
  Study Documents (Full-Text)

Documents provided by University of Alberta:

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Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT03727321     History of Changes
Other Study ID Numbers: Pro00076642
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: May 2, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: All individual participant data will be kept private and not distributed to other researchers outside of our study group. After the study is done, we will keep data stored for 25 years.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Alberta:
Fecal microbial transplant
obesity
metabolic syndrome
Additional relevant MeSH terms:
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Obesity
Metabolic Syndrome
Syndrome
Disease
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Dimenhydrinate
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action