Administration of Hydroxychloroquine (Plaquenil) to African Americans and Hispanics for the Treatment of Mild to Severe Ulcerative Colitis

The objective of this study is to assess the efficacy of hydroxychloroquine (HCQ) when combined with Mesalamine in reducing clinical and histologic disease activity in patients who have active mild to severe Ulcerative Colitis (UC) and also to assess the immunological effects of hydroxychloroquine in this population. These outcomes will be evaluated both clinically and experimentally. In vitro, flow cytometry will be employed to measure the expression of CTLA-4 on activated CD4+CD25+CD127- Tregs from patients prior to treatment with HCQ, and then at the end of a 4 month follow up period. Suppression assays will be used to determine the functional capacity of the patient derived Tregs. Clinically, patients will be monitored for remission as defined by reduction in patient reported stool frequency and rectal bleeding (mayo sub-score 0 or 1) and endoscopically, by improvement in mucosal appearance (mayo sub-score 0 or 1), all objective measures in the mayo score.

Study Overview

• Status: Active, not recruiting
• Conditions: Ulcerative Colitis (Disorder)
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Mesalamine

Detailed Description

This is a single arm study to evaluate the efficacy and immunological effect of administering Hydroxychloroquine to patients of non-European ancestry who have active mild to severe Ulcerative Colitis in spite of Mesalamine therapy. 10 Participants will be recruited in Icahn School of Medicine at Mount Sinai and 10 in Emory University (20 across all sites).

Participants 18 years and above who identify as an individual of non-European ancestry with a diagnosis of Ulcerative Colitis will be approached for the study. Participants will be recruited from Mount Sinai IBD center prior to their standard of care endoscopy. Participants who meet the study's inclusion criteria i.e. If they currently have active disease, they will be able to receive the research medication.

Participants will be administered 400mg hydroxychloroquine tablets orally for four months in addition to Mesalamine. Pre and post medication clinical, endoscopic and immunological assessments will be compared. Participants will also be followed up with bi-monthly phone calls. Participants will have a post medication colonoscopy at the end of the 4 month period.

There is a risk of retinopathy and cardiomyopathy associated with long term use of the study drug at doses greater than 6.5mg/kg for more than 5 years. Participants will be screened for existing eye and heart disease and monitored pre and post medication for any new adverse effects.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai/Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical diagnosis of mild to severe active Ulcerative Colitis (confirmed by endoscopy at screening),
• Currently taking mesalamine,
• Be an individual of non-European ancestry.
• Adult 18 years and older

Exclusion Criteria

• Current use of biologics, steroids or other UC medications not including mesalamine.
• Presence of hepatic or renal insufficiency
• Pregnancy or lactation
• Known allergic reactions to components of the Hydroxychloroquine, Chloroquine or quinine products.
• Any pre-existing macular disease or cardiac disease.
• Treatment with another investigational drug or other intervention within 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesalamine and Hydroxychloroquine; All participants will be on Mesalamine and Hydroxychloroquine	Drug: Hydroxychloroquine; 400mg of hydroxychloroquine per oral daily; Drug: Mesalamine; the participant will maintain their current standard of care dose which can range from 1.5g to 4.8g of mesalamine per oral daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in surface CTLA4 expression	Flow cytometry will be used to measure the expression of CTLA-4 on activated CD4+CD25+CD127- Tregs from patients prior to treatment with Hydroxychloroquine, and then at the end of a 4 month follow up period.	baseline and 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Endoscopy Mayo Score	Endoscopic remission will be measured using the mayo score which ranges from 0-3 with 0 meaning remission and 3 indication severe disease. Premedication endoscopy mayo score will be compared to end of study mayo score (at 4 months)	baseline and 4 months
Change in Partial Mayo Score	Change in patient reported symptoms for stool frequency and rectal bleeding are objective measures in the partial mayo score which ranges from 0-3 for both parameters. A score of zero indicates remission and a score on 3 indicates severe disease. Pre-medication partial mayo scores will be compared to end of study partial mayo scores (at 4 months)	baseline and 4 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Crohn's and Colitis Foundation
• Investigators: Principal Investigator: Judy H Cho, MD, ICAHN School of Medicine at Mount Sinai; Principal Investigator: Subra Kugathasan, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: October 20, 2021
• First Submitted That Met QC Criteria: November 10, 2021
• First Posted (Actual): November 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Inflammatory Bowel Disease; Hydroxychloroquine; CTLA-4; Plaquenil; Non European Ancestry
• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Ulcer; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Hydroxychloroquine; Mesalamine
• Other Study ID Numbers: GCO 20-0187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. To achieve aims in the approved proposal. Investigators should contact study team.
• IPD Sharing Supporting Information Type: SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No