Therapeutic Modulation of the Intestinal Creatine Kinase System in Inflammatory Bowel Disease (IBD) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Colitis, Ulcerative	Drug: Creatine monohydrate Other: Placebo	Early Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator) Primary Purpose: Treatment
Official Title:	Therapeutic Modulation of the Intestinal Creatine Kinase System in Inflammatory Bowel Disease (IBD)

Resource links provided by NLM:

MedlinePlus related topics: Ulcerative Colitis

Drug Information available for: Creatine monohydrate

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:

Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis. [ Time Frame: 8 weeks ]
As defined by the Mayo endoscopic score for ulcerative colitis.

Secondary Outcome Measures:

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.


Estimated Enrollment:	12
Study Start Date:	April 2016
Estimated Study Completion Date:	December 2017
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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.	Other: Placebo Other Name: 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

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02463305

Contacts


Contact: Jesse Bright, MS	(303) 724-7875	jesse.2.bright@ucdenver.edu
Contact: Carlene Chun, MD, PhD	303-724-1857	carlene.chun@ucdenver.edu

Locations


United States, Colorado
University of Colorado Hospital	Recruiting
Denver, Colorado, United States

Sponsors and Collaborators

University of Colorado, Denver

Investigators


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

More Information


Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT02463305 History of Changes
Other Study ID Numbers:	13-3054 UL1TR001082 ( U.S. NIH Grant/Contract )
Study First Received:	May 27, 2015
Last Updated:	January 11, 2017

Keywords provided by University of Colorado, Denver:


Colitis, ulcerative Inflammatory bowel diseases

Additional relevant MeSH terms:


Colitis Ulcer Intestinal Diseases Inflammatory Bowel Diseases Colitis, Ulcerative	Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Colonic Diseases Pathologic Processes

ClinicalTrials.gov processed this record on July 14, 2017