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

Primary Purpose

Colitis, Ulcerative

Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Creatine monohydrate
Placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colitis, Ulcerative focused on measuring Colitis, ulcerative, Inflammatory bowel diseases

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Colorado Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Treatment arm

Placebo arm

Optional Open-Label Treatment arm

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis.
As defined by the Mayo endoscopic score for ulcerative colitis.

Secondary Outcome Measures

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

Full Information

First Posted
May 27, 2015
Last Updated
April 3, 2023
Sponsor
University of Colorado, Denver
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1. Study Identification

Unique Protocol Identification Number
NCT02463305
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Withdrawn
Why Stopped
inability to enroll
Study Start Date
August 2022 (Anticipated)
Primary Completion Date
March 1, 2023 (Actual)
Study Completion Date
March 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colitis, Ulcerative
Keywords
Colitis, ulcerative, Inflammatory bowel diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo arm
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Optional Open-Label Treatment arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Creatine monohydrate
Intervention Description
21 grams creatine monohydrate total per day
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Dextrose
Intervention Description
7 grams of dextrose dissolved in 500mL water, taken three times daily
Primary Outcome Measure Information:
Title
Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis.
Description
As defined by the Mayo endoscopic score for ulcerative colitis.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Clinical response in ulcerative colitis disease activity.
Description
As defined by the Mayo composite score for ulcerative colitis.
Time Frame
8 weeks
Title
Intestinal permeability
Description
As measured by urinary saccharide excretion
Time Frame
8 weeks
Title
Patient symptom severity
Description
As measured by inflammatory bowel disease questionnaire (IBDQ), simple Crohn's and colitis activity index (SCCAI), and Mayo composite scores.
Time Frame
8 weeks
Title
Colonic inflammation
Description
As assessed by fecal calprotectin, CRP, and histologic scoring.
Time Frame
8 weeks
Title
Creatine kinase modulation
Description
As assessed by CK transcript and protein in colonic tissue and serum levels.
Time Frame
8 weeks
Title
Clinical remission of ulcerative colitis disease activity.
Description
As defined by the Mayo composite score for ulcerative colitis.
Time Frame
8 weeks
Title
Creatine modulation
Description
As defined by colonic tissue and serum levels.
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Gerich, MD
Organizational Affiliation
University of Colorado Denver, Division of Gastroenterology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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