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

Overseen By Lucy Smigiel, MPH

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Colorado, Denver

Must be taking: Mesalamine, Thiopurines

Must not be taking: Anti-TNF, Corticosteroids, NSAIDs, others

Disqualifiers: Pregnancy, Severe UC, Major comorbidities, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

Trial Summary

What is the purpose of this trial?

This trial studies how creatine monohydrate affects ulcerative colitis. Creatine provides energy to colon cells, helping them form a tight barrier that may reduce inflammation. Creatine is critical for maintaining intestinal health under inflammatory stress.

Will I have to stop taking my current medications?

The trial allows certain medications like mesalamine and thiopurines if they have been used at stable doses for a specified period. However, you must stop using over-the-counter supplements and certain medications like NSAIDs and ACE inhibitors two weeks before and during the study.

What data supports the effectiveness of the drug Creatine monohydrate?

Research shows that Creatine monohydrate can increase strength in patients with neuromuscular disease and improve high-intensity exercise performance. It is also widely used to enhance athletic performance, particularly in activities involving short bursts of high-intensity effort. ^{1 2 3 4 5}

Is creatine monohydrate safe for human use?

Creatine monohydrate is generally considered safe for healthy adults when taken at recommended doses (up to 3 grams per day). Some side effects like weight gain and gastrointestinal issues have been reported, but serious adverse effects are rare. It's important to ensure the product is free from contaminants and to consult a healthcare provider, especially for higher doses or if you have health concerns. ^{2 4 6 7 8}

How does creatine monohydrate differ from other treatments for this condition?

Creatine monohydrate is unique because it enhances muscle performance during short, high-intensity exercises by increasing the muscle's creatine and phosphocreatine levels, which helps produce energy quickly. This makes it particularly beneficial for vegetarians who have lower natural creatine stores compared to those who consume meat. ^{5 6 9 10 11}

Research Team

Mark Gerich, MD

Principal Investigator

University of Colorado Denver, Division of Gastroenterology

Eligibility Criteria

Inclusion Criteria

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 are 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.

Exclusion Criteria

Diagnosis of severe UC (Mayo Score > 10)

You have taken medications called anti-TNF agents or oral/rectal corticosteroids recently.

Evidence or history of toxic megacolon

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive creatine monohydrate or placebo for 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants from the placebo arm may opt into continuation of creatine monohydrate treatment for 8 weeks

8 weeks

Treatment Details

Interventions

• Creatine monohydrate
• Placebo

Participant Groups

Group I: Treatment arm Experimental Treatment 1 Intervention

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.

Group II: Optional Open-Label Treatment arm Experimental Treatment 1 Intervention

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.

Group III: Placebo arm Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Findings from Research

In a study involving 36 resistance-trained individuals, traditional creatine monohydrate (CrM) supplementation was found to be more effective than buffered creatine (KA) in increasing muscle creatine content and improving strength, with no significant differences in side effects reported between the two forms.

The results showed that neither the recommended lower dose of KA nor the higher equivalent loading dose provided any additional benefits over CrM, challenging claims that buffered creatine is superior in efficacy or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate. Jagim, AR., Oliver, JM., Sanchez, A., et al.[2021]

A systematic review of 29 studies involving 951 female participants found no serious adverse outcomes or deaths associated with creatine monohydrate (CrM) supplementation, indicating it is safe for use in women.

There were no significant differences in total adverse events, gastrointestinal issues, or weight gain between those taking CrM and those not, suggesting that CrM does not increase the risk of these complications in females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis. de Guingand, DL., Palmer, KR., Snow, RJ., et al.[2021]

In a pilot study with 81 patients and a follow-up study with 21 patients, creatine monohydrate supplementation significantly increased strength measures, including handgrip and knee extensor strength.

The treatment involved administering 10 g daily for 5 days, followed by 5 g daily for another 5 days, demonstrating that short-term creatine use can effectively enhance high-intensity strength in individuals with neuromuscular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine monohydrate increases strength in patients with neuromuscular disease. Tarnopolsky, M., Martin, J.[2019]

Creatine monohydrate is effective in enhancing athletic performance, particularly for activities involving repeated short bursts of high-intensity effort, with significant improvements in force production across various sports, ages, and sexes.

While creatine shows benefits for activities like jumping, sprinting, and cycling, it does not significantly aid in preventing muscle damage or soreness, and there is limited evidence for its effectiveness in endurance activities. Additionally, no strong evidence suggests adverse effects from short-term use, but long-term safety remains unstudied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine supplementation and exercise performance: recent findings. Bemben, MG., Lamont, HS.[2022]

Creatine monohydrate is generally considered safe for healthy adults at a daily intake of 3 grams, with some minor side effects like gastrointestinal issues and muscle cramps reported.

While most creatine forms are unlikely to pose safety concerns, there are specific safety concerns associated with creatine orotate, creatine phosphate, and magnesium creatine chelate, indicating that not all creatine supplements are equally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. Andres, S., Ziegenhagen, R., Trefflich, I., et al.[2018]

Creatine monohydrate is an effective sports supplement that helps maintain high-energy phosphate levels during exercise, leading to benefits like increased muscle mass and potential neural protection.

While creatine supplementation has many positive effects, there are concerns about side effects such as muscle cramping and the presence of impurities, which warrant careful consideration of its safety and quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine: are the benefits worth the risk? Brudnak, MA.[2013]

Creatine supplementation significantly increases creatine levels in vegetarians, often surpassing those found in omnivores, and enhances muscle mass, strength, and endurance, making it beneficial for vegetarian athletes.

While creatine improved various physical and cognitive performance metrics in vegetarians, the evidence on whether it enhances exercise performance more than in omnivores remains mixed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of Creatine Supplementation for Vegetarians Compared to Omnivorous Athletes: A Systematic Review. Kaviani, M., Shaw, K., Chilibeck, PD.[2020]

Creatine monohydrate effectively enhances muscle performance during short-duration, high-intensity exercises, with a recommended loading dose of 0.3 g·kg·d for 5 to 7 days followed by a maintenance dose of 0.03 g·kg·d for 4 to 6 weeks, although loading is not strictly necessary.

Creatine is generally safe with few side effects, primarily causing transient water retention; however, there are concerns about potential liver and kidney complications when taken in high doses or combined with other supplements over extended periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine supplementation. Hall, M., Trojian, TH.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Potential benefits of creatine monohydrate supplementation in the elderly. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Creatine monohydrate increases strength in patients with neuromuscular disease. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Creatine supplementation and exercise performance: recent findings. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Creatine as nutritional supplementation and medicinal product. [2017]

7. Germany pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Creatine: are the benefits worth the risk? [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Benefits of Creatine Supplementation for Vegetarians Compared to Omnivorous Athletes: A Systematic Review. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Creatine supplementation. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. [2022]