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

NCT02463305 | Withdrawn Early Phase 1 DMC FDA Drug

• 2 other identifiers: 13-3054UL1TR001082
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Colitis, Ulcerative

Keywords

Colitis, ulcerative; Inflammatory bowel diseases

Outcome Measures

Primary Outcomes (1)

• Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis.

  As defined by the Mayo endoscopic score for ulcerative colitis.

  8 weeks

Secondary Outcomes (7)

• Clinical response in ulcerative colitis disease activity.

  8 weeks

• Intestinal permeability

  8 weeks

• Patient symptom severity

  8 weeks

• Colonic inflammation

  8 weeks

• Creatine kinase modulation

  8 weeks

Study Arms (3)

Treatment arm

EXPERIMENTAL

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

Placebo arm

PLACEBO COMPARATOR

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

Optional Open-Label Treatment arm

EXPERIMENTAL

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

Interventions

Creatine monohydrate DRUG

21 grams creatine monohydrate total per day

Optional Open-Label Treatment arm; Treatment arm

Placebo OTHER

7 grams of dextrose dissolved in 500mL water, taken three times daily

Also known as: Dextrose

Placebo arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Denver, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

Creatine; Glucose

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• Mark Gerich, MD

  University of Colorado Denver, Division of Gastroenterology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: June 4, 2015
• Study Start: August 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: April 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)