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

University of Colorado Denver (CU Denver)

Status and phase: Withdrawn; Early Phase 1

Conditions: Colitis, Ulcerative

Treatments: Other: Placebo; Drug: Creatine monohydrate

Study type: Interventional

Funder types: Other

Identifiers

NCT02463305

13-3054

UL1TR001082 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

0 participants in 3 patient groups, including a placebo group

Treatment arm

Experimental group

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.

Treatment:

Drug: Creatine monohydrate

Placebo arm

Placebo Comparator group

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.

Treatment:

Other: Placebo

Optional Open-Label Treatment arm

Experimental group

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.

Treatment:

Drug: Creatine monohydrate