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

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.

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.