Hydroxychloroquine + Mesalamine for Ulcerative Colitis

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

3 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests hydroxychloroquine with mesalamine for ulcerative colitis. It focuses on patients of non-European ancestry who still have symptoms despite using mesalamine. Hydroxychloroquine may help by controlling the immune system and reducing inflammation. Mesalamine has a well-established role in the management of ulcerative colitis.

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.

What data supports the effectiveness of the drug Hydroxychloroquine + Mesalamine for treating ulcerative colitis?

Preliminary studies have shown that chloroquine, which is similar to hydroxychloroquine, is effective in treating mild to moderately active ulcerative colitis, with 60% of patients achieving complete remission in a trial. This suggests that hydroxychloroquine may also be beneficial for ulcerative colitis. ^{1 2 3 4 5}

Is Hydroxychloroquine safe for humans?

Hydroxychloroquine has been associated with several side effects, including eye problems like retinal toxicity, skin reactions, and gastrointestinal issues. Some severe reactions can occur, such as heart problems and serious skin conditions, but these are less common. ^{6 7 8 9 10}

How is the drug combination of Hydroxychloroquine and Mesalamine unique for treating ulcerative colitis?

This treatment is unique because it combines Hydroxychloroquine, typically used for conditions like malaria and rheumatoid arthritis, with Mesalamine, a standard treatment for ulcerative colitis, potentially offering a novel approach by leveraging Hydroxychloroquine's anti-inflammatory properties alongside Mesalamine's targeted action in the colon. ^{11 12 13 14 15}

Research Team

subra kugathasan

Principal Investigator

Emory University

Judy H Cho

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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 18 years old or older.

I am currently taking mesalamine.

Only people who are not of European descent can participate.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Similar Short- and Long-term Colectomy Rates with Ciclosporin and Infliximab Treatment in Hospitalised Ulcerative Colitis Patients. [2017]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Systematic review and network meta-analysis of treatment for moderate-to-severe ulcerative colitis. [2022]

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

Chloroquine for mild to moderately active ulcerative colitis: comparison with sulfasalazine. [2013]

4. England pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

What do malaria, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis have in common? [2019]

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

Retinal toxicity secondary to Plaquenil therapy. [2016]

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

Association Between Autoantibody Phenotype and Cutaneous Adverse Reactions to Hydroxychloroquine in Dermatomyositis. [2019]

8. France pubmed.ncbi.nlm.nih.gov

[Hallucinations during treatment with hydrochloroquine]. [2019]

9. Italy pubmed.ncbi.nlm.nih.gov

The safety profile of hydroxychloroquine: major cutaneous and extracutaneous adverse events. [2022]

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

Highly Accelerated Onset of Hydroxychloroquine Macular Retinopathy. [2020]

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

Protective Effect of Asacol in Combination with Pantoprazole in Ulcerative Colitis Patients Who Defecate Asacol Tablets Intactly: A Clinical Trial Study. [2022]

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

An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis. A randomized, placebo-controlled trial. The Mesalamine Study Group. [2019]

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

Asacol (mesalamine). [2019]

14. England pubmed.ncbi.nlm.nih.gov

The cost-utility of high dose oral mesalazine for moderately active ulcerative colitis. [2022]

15. England pubmed.ncbi.nlm.nih.gov

Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study. [2022]