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

Early Phase 1

Withdrawn

• Conditions: Colitis, Ulcerative
• Interventions: Drug: Creatine monohydrate; Other: Placebo

• Registration Number: NCT02463305
• Lead Sponsor: University of Colorado, Denver

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-05-27
• Study First Submitted QC: 2015-06-01
• Study First Posted: 2015-06-04
• Study Start: 2022-08
• Primary Completion: 2023-03-01
• Study Completion: 2023-03-01
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-03
• Last Update Posted: 2023-04-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment arm	Creatine monohydrate	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.
Placebo arm	Placebo	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.
Optional Open-Label Treatment arm	Creatine monohydrate	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.

Primary Outcome Measures

Name	Time	Method
Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis.	8 weeks	As defined by the Mayo endoscopic score for ulcerative colitis.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Colorado Hospital; 🇺🇸 Denver, Colorado, United States