Therapeutic Modulation of the Intestinal Creatine Kinase System in Inflammatory Bowel Disease (IBD)

• Clinical response in ulcerative colitis disease activity. [ Time Frame: 8 weeks ]
  As defined by the Mayo composite score for ulcerative colitis.
• Intestinal permeability [ Time Frame: 8 weeks ]
  As measured by urinary saccharide excretion
• Patient symptom severity [ Time Frame: 8 weeks ]
  As measured by inflammatory bowel disease questionnaire (IBDQ), simple Crohn's and colitis activity index (SCCAI), and Mayo composite scores.
• Colonic inflammation [ Time Frame: 8 weeks ]
  As assessed by fecal calprotectin, CRP, and histologic scoring.
• Creatine kinase modulation [ Time Frame: 8 weeks ]
  As assessed by CK transcript and protein in colonic tissue and serum levels.
• Clinical remission of ulcerative colitis disease activity. [ Time Frame: 8 weeks ]
  As defined by the Mayo composite score for ulcerative colitis.
• Creatine modulation [ Time Frame: 8 weeks ]
  As defined by colonic tissue and serum levels.

• Clinical response in ulcerative colitis disease activity. [ Time Frame: 8 weeks ]
  As defined by the Mayo composite score for ulcerative colitis.
• Intestinal permeability [ Time Frame: 8 weeks ]
  As measured by urinary saccharide excretion and serum lipopolysaccharide (LPS) level.
• Patient symptom severity [ Time Frame: 8 weeks ]
  As measured by inflammatory bowel disease questionnaire (IBDQ), simple Crohn's and colitis activity index (SCCAI), and Mayo composite scores.
• Colonic inflammation [ Time Frame: 8 weeks ]
  As assessed by fecal calprotectin, CRP, and histologic scoring.
• Creatine kinase modulation [ Time Frame: 8 weeks ]
  As assessed by CK transcript and protein in colonic tissue and serum levels.
• Clinical remission of ulcerative colitis disease activity. [ Time Frame: 8 weeks ]
  As defined by the Mayo composite score for ulcerative colitis.
• Creatine modulation [ Time Frame: 8 weeks ]
  As defined by colonic tissue and serum levels.

• Drug: Creatine monohydrate
• Other: Placebo
  Other Name: Dextrose

• Experimental: Treatment arm
  6 patients with mild-moderate ulcerative colitis treated with creatine monohydrate 21grams per day in three divided doses taken with water for 8 weeks.
  Intervention: Drug: Creatine monohydrate
• Placebo Comparator: Placebo arm
  6 patients with mild-moderate ulcerative colitis treated with placebo (matching creatine monohydrate) 21 grams per day in three divided doses taken with water for 8 weeks.
  Intervention: Other: Placebo
• Experimental: Optional Open-Label Treatment arm
  Up to 6 patients, who were randomized to the placebo arm, will be given the option to continue with open-label creatine monohydrate treatment at 21 grams per day in three divided doses, taken with water, for 8 weeks. Only non-invasive testing will be performed.
  Intervention: Drug: Creatine monohydrate

Inclusion Criteria:

• Male or female patients aged 18-70 years old with mild- to moderately-active UC that extends at least 15 cm proximal to the anal verge (i.e. not proctitis) as defined by a Mayo Score of 3-10, with an endoscopic subscore ≥ 1.
• Allowed concomitant medications will include mesalamine compounds if used for at least 8 weeks and at a stable dose for at least 4 weeks, as well as thiopurines (azathioprine, 6-mercaptopurine) if used at a stable dose for at least 3 months.

Exclusion Criteria:

• Abnormal baseline laboratory tests:

  • Albumin < 3.0 g/dL
  • ALT, AST, total bilirubin, or alkaline phosphatase > 1.5 x ULN
  • Potassium < 3.0 mmol/L or > 5.5 mmol/L
  • Creatinine or cystatin C > ULN
  • WBC ≤ 3000
  • Platelets ≤ 105
  • Hemoglobin ≤ 10g/dL
  • Positive stool test for Clostridium difficile, ova and parasites, or routine stool culture
• Pregnancy (as confirmed by urine pregnancy test at study outset), stated desire to become pregnant during the study period, or refusal/inability to use effective methods of contraception during the study period.
• Concomitant major comorbidities (renal, hepatic, cardiac, pulmonary or malignancy) to include any medical conditions requiring therapeutic anti-coagulation or anti-platelet therapy.
• Diagnosis of severe UC (Mayo Score > 10)
• Evidence or history of toxic megacolon
• Patients who received anti-TNF agents within 3 months of screening, or who used oral or rectal corticosteroids within 4 weeks of screening will be excluded.
• Use of over-the-counter herbal or dietary supplements (excluding vitamin and minerals) two weeks prior to or during the study period.
• Use of known nephrotoxic medications (including non-steroidal anti-inflammatory drugs (NSAIDs), cyclosporin A, tacrolimus, aminoglycoside antibiotics, diuretics, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor blockers) 2 weeks prior to or during the study period
• Prior surgical bowel resections (excluding appendectomy)
• Local or systemic complications or other pathological states requiring therapy with corticosteroids and/or immunosuppressive agents.