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

Study Overview
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Brief Summary
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This study plans to learn more about the effects that creatine monohydrate has on disease activity in ulcerative colitis. Creatine is a substance that is naturally produced by the body and is found in foods, such as meat and fish. Creatine helps to provide energy to some body tissues, such as the colon. In the colon, this energy allows cells to form a tight barrier between molecules in digested food and bacteria and the body's infection-fighting cells within the colon underneath this barrier. If the barrier becomes leaky molecules may pass through and lead to inflammation. This leakiness may contribute to the colon inflammation seen in ulcerative colitis.

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

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Creatine monohydrate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>6 patients with mild-moderate ulcerative colitis treated with creatine monohydrate 21 grams per day in three divided doses taken with water for 8 weeks. | Drug: Creatine monohydrate<br>* 21 grams creatine monohydrate total per day<br>|
| Placebo Comparator: Placebo arm<br>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. | Other: Placebo<br>* 7 grams of dextrose dissolved in 500mL water, taken three times daily<br>* Other names: Dextrose;|
| Experimental: Optional Open-Label Treatment arm<br>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. | Drug: Creatine monohydrate<br>* 21 grams creatine monohydrate total per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis. | As defined by the Mayo endoscopic score for ulcerative colitis. | 8 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colitis, ulcerative, Inflammatory bowel diseases