Targeting FMO-Mediated TMAO Formation in Kidney Disease (TMAO) Study (TMAO)

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Kidney Diseases
• Intervention / Treatment: Dietary supplement: Commercially available Diindolylmethane; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects 18 years of age, but not more than 75 years of age at the time of enrollment.
2. Must be able to provide signed and dated informed consent.
3. Medical diagnosis of chronic kidney disease (eGFR ≤ 60 ml/min/1.73m2 )

Exclusion Criteria:

1. Vital signs outside of acceptable range at Screening Visit

2. 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.

3. 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.
4. Chronic, clinically significant hepatic abnormality (i.e. elevated 3X ULN ALT/AST), as determined by medical history or physical examination.
5. History of cancer except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision.
6. 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.
7. 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.
8. Any confirmed or suspected condition/state of immunosuppression or immunodeficiency.
9. 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.
10. Patient who may be pregnant or lactating.
11. Not willing to abstain from cruciferous vegetable (i.e. cabbage, brussels sprouts, garden cress, mustard greens, turnips, broccoli, collard greens , cauliflower, kale) consumption.
12. Current smoking.
13. Unwilling or unable to adhere to study procedures or instructions.
14. Patients taking any of the following medications, methimazole, alosetron, duloxetine, ramelteon, tasimelteon, theophylline, tizanidine, clozapine, pirfenidone and ramosetron.
15. Allergies to corn or soy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; This crossover design will include 4 weeks of diindolylmethane and 4 weeks of matching placebo assignment.	Dietary supplement: Commercially available Diindolylmethane; Commercially available Diindolylmethane is a compound derived from cruciferous vegetables (e.g. broccoli); Other: Placebo; A matching placebo capsule will be compounded by the UPMC Investigational Drug Service
Experimental: Commercially available Diindolylmethane; This crossover design will include 4 weeks of diindolylmethane and 4 weeks of matching placebo assignment.	Dietary supplement: Commercially available Diindolylmethane; Commercially available Diindolylmethane is a compound derived from cruciferous vegetables (e.g. broccoli); Other: Placebo; A matching placebo capsule will be compounded by the UPMC Investigational Drug Service

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TMAO	Serum TMAO concentrations	12 weeks.

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Thomas D Nolin, PharmD, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2018
• Primary Completion (Actual): April 18, 2019
• Study Completion (Actual): August 30, 2019

Study Registration Dates

• First Submitted: May 4, 2017
• First Submitted That Met QC Criteria: May 10, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 24, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Cardiovascular Diseases; Kidney Diseases; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; 3,3'-diindolylmethane
• Other Study ID Numbers: PRO16090410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No