Clinical trial NCT03152097: Targeting FMO-Mediated TMAO Formation in Kidney Disease (TMAO) Study
Official title: Targeting FMO-Mediated TMAO Formation in Kidney Disease (TMAO) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Kidney Diseases
Cardiovascular Diseases
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2017-05-12
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: TMAO
timeFrame: 12 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Thomas D Nolin, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References: