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

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.

Study Overview

• Status: Withdrawn
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: Creatine monohydrate; Other: Placebo

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Lucy Smigiel, MPH; Phone Number: 3037249143; Email: lucy.smigiel@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm; 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; 21 grams creatine monohydrate total per day
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.	Other: Placebo; 7 grams of dextrose dissolved in 500mL water, taken three times daily; Other Names: Dextrose
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.	Drug: Creatine monohydrate; 21 grams creatine monohydrate total per day

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Mark Gerich, MD, University of Colorado Denver, Division of Gastroenterology

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2022
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: May 27, 2015
• First Submitted That Met QC Criteria: June 1, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Inflammatory bowel diseases; Colitis, ulcerative
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Inflammatory Bowel Diseases; Intestinal Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 13-3054; UL1TR001082 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No