Targeting FMO-Mediated TMAO Formation in Kidney Disease (TMAO) Study (TMAO)
Primary Purpose
Kidney Diseases, Cardiovascular Diseases
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Commercially available Diindolylmethane
Placebo
Sponsored by
About this trial
This is an interventional other trial for Kidney Diseases
Eligibility Criteria
Inclusion Criteria:
- Male or female subjects 18 years of age, but not more than 75 years of age at the time of enrollment.
- Must be able to provide signed and dated informed consent.
- Medical diagnosis of chronic kidney disease (eGFR ≤ 60 ml/min/1.73m2 )
Exclusion Criteria:
- Vital signs outside of acceptable range at Screening Visit
Use of any of the following drugs within the last 3 months:
Systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral); oral, intravenous, intramuscular, nasal or inhaled corticosteroids; cytokines; methotrexate or immunosuppressive cytotoxic agents; anti-diarrheal agents, bile acid sequestrants.
- Consuming commercial probiotics including tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component. Ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply.
- Chronic, clinically significant hepatic abnormality (i.e. elevated 3X ULN ALT/AST), as determined by medical history or physical examination.
- History of cancer except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision.
- Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet.
- Recent history of chronic alcohol consumption defined as more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or five 5-ounce servings of wine per day.
- Any confirmed or suspected condition/state of immunosuppression or immunodeficiency.
- History of active uncontrolled gastrointestinal disorders or diseases including: Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis; irritable bowel syndrome (IBS) (moderate-severe); persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated); chronic constipation. Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time.
- Patient who may be pregnant or lactating.
- Not willing to abstain from cruciferous vegetable (i.e. cabbage, brussels sprouts, garden cress, mustard greens, turnips, broccoli, collard greens , cauliflower, kale) consumption.
- Current smoking.
- Unwilling or unable to adhere to study procedures or instructions.
- Patients taking any of the following medications, methimazole, alosetron, duloxetine, ramelteon, tasimelteon, theophylline, tizanidine, clozapine, pirfenidone and ramosetron.
- Allergies to corn or soy.
Sites / Locations
- University of Pittsburgh
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Commercially available Diindolylmethane
Arm Description
This crossover design will include 4 weeks of diindolylmethane and 4 weeks of matching placebo assignment.
This crossover design will include 4 weeks of diindolylmethane and 4 weeks of matching placebo assignment.
Outcomes
Primary Outcome Measures
TMAO
Serum TMAO concentrations
Secondary Outcome Measures
Full Information
NCT ID
NCT03152097
First Posted
May 4, 2017
Last Updated
September 20, 2019
Sponsor
University of Pittsburgh
1. Study Identification
Unique Protocol Identification Number
NCT03152097
Brief Title
Targeting FMO-Mediated TMAO Formation in Kidney Disease (TMAO) Study
Acronym
TMAO
Official Title
Targeting FMO-Mediated TMAO Formation in Kidney Disease (TMAO) Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
March 30, 2018 (Actual)
Primary Completion Date
April 18, 2019 (Actual)
Study Completion Date
August 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pittsburgh
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The project will investigate the modulation of flavin-containing monooxygenase (FMO) formation of the CVD risk factor trimethylamine-N-oxide (TMAO) in patients with kidney disease.
Detailed Description
Twelve patients with stage 3 to 4 kidney disease will receive an intervention for four weeks and a matching placebo in a crossover study design. Reduction of serum TMAO from baseline to end of intervention will be the primary endpoint.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Diseases, Cardiovascular Diseases
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
This crossover design will include 4 weeks of diindolylmethane and 4 weeks of matching placebo assignment.
Arm Title
Commercially available Diindolylmethane
Arm Type
Experimental
Arm Description
This crossover design will include 4 weeks of diindolylmethane and 4 weeks of matching placebo assignment.
Intervention Type
Dietary Supplement
Intervention Name(s)
Commercially available Diindolylmethane
Intervention Description
Commercially available Diindolylmethane is a compound derived from cruciferous vegetables (e.g. broccoli)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
A matching placebo capsule will be compounded by the UPMC Investigational Drug Service
Primary Outcome Measure Information:
Title
TMAO
Description
Serum TMAO concentrations
Time Frame
12 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female subjects 18 years of age, but not more than 75 years of age at the time of enrollment.
Must be able to provide signed and dated informed consent.
Medical diagnosis of chronic kidney disease (eGFR ≤ 60 ml/min/1.73m2 )
Exclusion Criteria:
Vital signs outside of acceptable range at Screening Visit
Use of any of the following drugs within the last 3 months:
Systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral); oral, intravenous, intramuscular, nasal or inhaled corticosteroids; cytokines; methotrexate or immunosuppressive cytotoxic agents; anti-diarrheal agents, bile acid sequestrants.
Consuming commercial probiotics including tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component. Ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply.
Chronic, clinically significant hepatic abnormality (i.e. elevated 3X ULN ALT/AST), as determined by medical history or physical examination.
History of cancer except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision.
Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet.
Recent history of chronic alcohol consumption defined as more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or five 5-ounce servings of wine per day.
Any confirmed or suspected condition/state of immunosuppression or immunodeficiency.
History of active uncontrolled gastrointestinal disorders or diseases including: Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis; irritable bowel syndrome (IBS) (moderate-severe); persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated); chronic constipation. Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time.
Patient who may be pregnant or lactating.
Not willing to abstain from cruciferous vegetable (i.e. cabbage, brussels sprouts, garden cress, mustard greens, turnips, broccoli, collard greens , cauliflower, kale) consumption.
Current smoking.
Unwilling or unable to adhere to study procedures or instructions.
Patients taking any of the following medications, methimazole, alosetron, duloxetine, ramelteon, tasimelteon, theophylline, tizanidine, clozapine, pirfenidone and ramosetron.
Allergies to corn or soy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas D Nolin, PharmD, PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Targeting FMO-Mediated TMAO Formation in Kidney Disease (TMAO) Study
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