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

NCT03152097 | Completed

• 1 other identifier: PRO16090410
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Diseases; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• TMAO

  Serum TMAO concentrations

  12 weeks.

Study Arms (2)

Placebo

PLACEBO COMPARATOR

This crossover design will include 4 weeks of diindolylmethane and 4 weeks of matching placebo assignment.

Dietary Supplement: Commercially available Diindolylmethane; Other: Placebo

Commercially available Diindolylmethane

EXPERIMENTAL

This crossover design will include 4 weeks of diindolylmethane and 4 weeks of matching placebo assignment.

Dietary Supplement: Commercially available Diindolylmethane; Other: Placebo

Interventions

Commercially available Diindolylmethane DIETARY_SUPPLEMENT

Commercially available Diindolylmethane is a compound derived from cruciferous vegetables (e.g. broccoli)

Commercially available Diindolylmethane; Placebo

Placebo OTHER

A matching placebo capsule will be compounded by the UPMC Investigational Drug Service

Commercially available Diindolylmethane; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 )

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

MeSH Terms

Conditions

Kidney Diseases; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Thomas D Nolin, PharmD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 4, 2017
• First Posted: May 12, 2017
• Study Start: March 30, 2018
• Primary Completion: April 18, 2019
• Study Completion: August 30, 2019
• Last Updated: September 24, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)