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

NCT ID: NCT03152097

Last Updated: 2019-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-30
• Study Completion Date: 2019-08-30

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.

Conditions

Kidney Diseases; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Commercially available Diindolylmethane

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo

Intervention Type: OTHER

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

Commercially available Diindolylmethane

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

Group Type: EXPERIMENTAL

Commercially available Diindolylmethane

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo

Intervention Type: OTHER

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

Interventions

Commercially available Diindolylmethane

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

Intervention Type: DIETARY_SUPPLEMENT

Placebo

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

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Thomas Nolin

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas D Nolin, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

PRO16090410

Identifier Type: -

Identifier Source: org_study_id