Hydroxychloroquine + Mesalamine for Ulcerative Colitis

Not currently recruiting at 1 trial location

Overseen By subra kugathasan

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: Mesalamine

Must not be taking: Biologics, Steroids

Disqualifiers: Hepatic, Renal, Pregnancy, Cardiac, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining hydroxychloroquine, an anti-inflammatory drug, with mesalamine improves treatment for Ulcerative Colitis (UC), a condition affecting the colon and causing symptoms like frequent diarrhea and bleeding. Researchers aim to determine if this combination can reduce disease activity and improve symptoms such as stool frequency and rectal bleeding. Individuals with mild to severe UC, currently taking mesalamine, and of non-European ancestry might be suitable for this trial. Researchers will closely monitor participants to observe changes in their symptoms over time. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

If you are currently taking mesalamine, you can continue using it during the trial. However, you must not be using biologics, steroids, or other medications for Ulcerative Colitis besides mesalamine.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that hydroxychloroquine is generally well-tolerated by people with inflammatory bowel diseases like Crohn's and ulcerative colitis. One study found that patients used hydroxychloroquine for an average of about 2.5 years, with some using it for up to 8 years, suggesting the treatment is usually safe for long-term use.

Mesalamine, another drug in the study, is also considered safe for long-term use. It is often used to treat ulcerative colitis and is known to be well-tolerated. Research indicates that mesalamine effectively treats active ulcerative colitis without major safety issues.

Overall, both treatments have a good safety record in patients with similar conditions. This suggests they might be safe when used together, although more research is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Ulcerative Colitis?

Researchers are excited about the combination of hydroxychloroquine and mesalamine for ulcerative colitis because it introduces a novel approach to managing the condition. Most treatments for ulcerative colitis, like mesalamine alone or corticosteroids, primarily focus on reducing inflammation in the colon. However, adding hydroxychloroquine, which is traditionally used for its immune-modulating properties in other conditions, could offer a dual mechanism by both calming inflammation and potentially modulating the immune system's response. This combination might enhance effectiveness or possibly reduce the reliance on more aggressive therapies like immunosuppressants, offering a new hope for patients.

What evidence suggests that this treatment might be an effective treatment for Ulcerative Colitis?

Research has shown that chloroquine, a drug similar to hydroxychloroquine, has helped people with mild to moderate ulcerative colitis. This suggests that hydroxychloroquine might have a similar effect. Mesalamine is already known to reduce swelling in ulcerative colitis. In this trial, all participants will receive a combination of mesalamine and hydroxychloroquine. Using these two treatments together could be more effective because they work in different ways. Early results suggest that this combination might reduce symptoms like frequent bowel movements and rectal bleeding, and improve the appearance of the colon lining. The goal of this combination is to help patients reach remission, where symptoms are significantly reduced or absent. ^{1 2 6 7 8}

Who Is on the Research Team?

subra kugathasan

Principal Investigator

Emory University

Judy H Cho

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for African American and Hispanic adults with mild to severe active Ulcerative Colitis, confirmed by endoscopy. Participants must be taking mesalamine but not biologics, steroids or other UC medications. They should not have liver or kidney issues, be pregnant or breastfeeding, have a history of allergic reactions to Hydroxychloroquine-related compounds, macular disease or cardiac disease.

Inclusion Criteria

I am currently taking mesalamine.

Only people who are not of European descent can participate.

Be an individual of non-European ancestry

Exclusion Criteria

I have a heart condition or a disease affecting my eyes.

I am currently using medication for ulcerative colitis, but not mesalamine.

Treatment with another investigational drug or other intervention within 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 400mg hydroxychloroquine tablets orally for four months in addition to Mesalamine

16 weeks

Bi-monthly phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a post-medication colonoscopy

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Hydroxychloroquine
• Mesalamine

Trial Overview The study tests the effectiveness of Hydroxychloroquine combined with Mesalamine in reducing symptoms and inflammation in Ulcerative Colitis patients. It also examines how this combination affects immune cells (Tregs) using lab techniques like flow cytometry and suppression assays over a 4-month period.

How Is the Trial Designed?

Group I: Mesalamine and Hydroxychloroquine Experimental Treatment 2 Interventions

All participants will be on Mesalamine and Hydroxychloroquine

Hydroxychloroquine is already approved in United States, European Union for the following indications:

Approved in United States as Plaquenil for:

• Malaria
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus

Approved in European Union as Plaquenil for:

• Malaria
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Crohn's and Colitis Foundation

Collaborator

Trials

44

Recruited

27,500+

Published Research Related to This Trial

Hydroxychloroquine, commonly used for rheumatological disorders, has been linked to a variety of adverse effects, particularly in women over 50, with skin rashes being the most common issue occurring within 4 weeks of treatment.

More severe adverse events, although rare, include serious skin reactions like Stevens-Johnson syndrome and systemic issues such as cardiotoxicity and retinopathy, highlighting the importance of monitoring patients on this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profile of hydroxychloroquine: major cutaneous and extracutaneous adverse events. Gisondi, P., Piaserico, S., Bordin, C., et al.[2022]

A 71-year-old woman experienced retinal toxicity after taking hydroxychloroquine for 5 years, highlighting the risk of ocular side effects, particularly toxic maculopathy, associated with this medication.

The only effective treatment for hydroxychloroquine toxicity is to discontinue the drug, but the toxic effects may continue to progress due to the slow clearance of the medication, emphasizing the importance of regular eye examinations before and during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal toxicity secondary to Plaquenil therapy. Hanna, B., Holdeman, NR., Tang, RA., et al.[2016]

In a study of 111 adults with dermatomyositis, 20.7% experienced skin eruptions after starting hydroxychloroquine, indicating a notable risk of adverse reactions in this population.

Patients with anti-SAE-1/2 autoantibodies had a significantly higher risk (50%) of developing skin eruptions, while those with anti-MDA-5 autoantibodies showed a protective effect, suggesting that specific autoantibody profiles can influence the safety of hydroxychloroquine treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Autoantibody Phenotype and Cutaneous Adverse Reactions to Hydroxychloroquine in Dermatomyositis. Wolstencroft, PW., Casciola-Rosen, L., Fiorentino, DF.[2019]

A 75-year-old woman experienced cenesthetic hallucinations and disorientation after 10 days of hydrochloroquine treatment for erosive plantar lichen planus, highlighting a rare neuropsychiatric side effect of the medication.

The patient's psychiatric symptoms resolved within a month after stopping hydrochloroquine, indicating that these side effects may be idiosyncratic and not related to dosage, which is important for clinicians to consider when prescribing this drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinations during treatment with hydrochloroquine]. Ferraro, V., Mantoux, F., Denis, K., et al.[2019]

A 61-year-old woman developed permanent bilateral bull's-eye retinopathy after taking hydroxychloroquine (HCQ) for only 2 months, despite not having known risk factors for retinal toxicity.

This case highlights the need for additional screening tests for HCQ toxicity, as the patient experienced adverse effects even with a lower drug load and without common risk factors, suggesting other underlying mechanisms may contribute to toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly Accelerated Onset of Hydroxychloroquine Macular Retinopathy. Stern, EM., Johnson, JS., Mazzulla, DA.[2020]

Infliximab is identified as the most effective treatment for inducing clinical response and remission in patients with moderate-to-severe ulcerative colitis, based on a systematic review and Bayesian network meta-analysis of 14 clinical trials.

Tofacitinib is noted for having the highest rate of maintaining clinical remission, while ozanimod is highlighted as the best option for inducing mucosal healing, indicating that different treatments may be optimal for various stages of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and network meta-analysis of treatment for moderate-to-severe ulcerative colitis. Trigo-Vicente, C., Gimeno-Ballester, V., García-López, S., et al.[2022]

Golimumab is an effective treatment for ulcerative colitis, as demonstrated in a phase III double-blind trial, adding to the existing options for patients.

With the introduction of golimumab, there are now three anti-TNF therapies available for ulcerative colitis: infliximab, adalimumab, and golimumab, providing more choices for effective management of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IBD: Golimumab in ulcerative colitis: a 'ménage à trois' of drugs. Danese, S.[2021]

Citations

1. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05119140/

Trial | NCT05119140 The objective of this study is to assess the efficacy of hydroxychloroquine (HCQ) when combined with Mesalamine in reducing clinical and histologic disease ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05119140?term=hydroxychloroquine&aggFilters=status:rec%20act&viewType=Table&rank=5

NCT05119140 | Administration of Hydroxychloroquine ... The objective of this study is to assess the efficacy of hydroxychloroquine (HCQ) when combined with Mesalamine in reducing clinical and histologic disease ...

3. withpower.com withpower.com/trial/phase-2-colitis-ulcerative-10-2021-898a8

Hydroxychloroquine + Mesalamine for Ulcerative Colitis Preliminary studies have shown that chloroquine, which is similar to hydroxychloroquine, is effective in treating mild to moderately active ulcerative colitis, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8633581/

Chloroquine for mild to moderately active ulcerative colitis We conclude that short-duration chloroquine therapy is a safe and effective alternative to sulfasalazine in the treatment of mild to moderately active ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4723544/

Current medical therapy of inflammatory bowel disease Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. The Abacus Investigator Group ...

6. gidoctor.net gidoctor.net/hydroxychloroquine/

Hydroxychloroquine for Crohns Disease and Ulcerative ... The mean (±1SD) duration of hydroxychloroquine treatment for all patients was 132 (± 140) weeks (range 3 – 416 weeks). Both UC patients had marked improvement: ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11045479/

Combination treatment of inflammatory bowel disease The results showed that 5 out of 6 patients with active CD achieved clinical remission and 2 patients with severe arthritis showed significant clinical ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0889855305700583

MEDICAL THERAPY FOR INFLAMMATORY BOWEL ... Robinson, et al. Mesalamine capsules for the treatment of active ulcerative colitis: Results of a controlled trial. Am J Gastroenterol, 88 (1993), pp. 1188 ...