Clinical trial NCT02463305: Therapeutic Modulation of the Intestinal Creatine Kinase System in Inflammatory Bowel Disease (IBD)
Official title: Therapeutic Modulation of the Intestinal Creatine Kinase System in Inflammatory Bowel Disease (IBD)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Colitis, Ulcerative
Keywords: Colitis, ulcerative
Inflammatory bowel diseases
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2015-06-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis.
timeFrame: 8 weeks
Secondary outcomes:
measure: Clinical response in ulcerative colitis disease activity.
timeFrame: 8 weeks
measure: Intestinal permeability
timeFrame: 8 weeks
measure: Patient symptom severity
timeFrame: 8 weeks
measure: Colonic inflammation
timeFrame: 8 weeks
measure: Creatine kinase modulation
timeFrame: 8 weeks
measure: Clinical remission of ulcerative colitis disease activity.
timeFrame: 8 weeks
measure: Creatine modulation
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado Denver, Division of Gastroenterology
name: Mark Gerich, MD
role: PRINCIPAL_INVESTIGATOR
References: