HCQ for Non Europeans With Mild to Severe UC

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Recruiting

CT.gov ID

NCT05119140

Collaborator

Crohn's and Colitis Foundation (Other)

Enrollment

Locations

Arm

17.7

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis (Disorder)	Drug: Hydroxychloroquine Drug: Mesalamine	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is an Open Label study with blinded scorer for endoscopy and pathology reports.This is an Open Label study with blinded scorer for endoscopy and pathology reports.

Masking:

None (Open Label)

Masking Description:

The gastroenterologist who will review pre- and post-intervention endoscopy and pathology reports will be masked to any and all information about the study participants including disease severity and medication.

Primary Purpose:

Basic Science

Official Title:

Administration of Hydroxychloroquine (Plaquenil) to Individuals of Non-European Ancestry for the Treatment of Mild to Severe Ulcerative Colitis.

Actual Study Start Date :

Jun 10, 2022

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in surface CTLA4 expression [baseline and 4 months]
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.

Secondary Outcome Measures

Change in Endoscopy Mayo Score [baseline and 4 months]
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)
Change in Partial Mayo Score [baseline and 4 months]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University School of Medicine	Atlanta	Georgia	United States	30322
2	Icahn School of Medicine at Mount Sinai/Mount Sinai Hospital	New York	New York	United States	10029

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai
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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Judy Cho, Dean of Translational Genetics, Director, The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai

ClinicalTrials.gov Identifier:

NCT05119140

Other Study ID Numbers:

GCO 20-0187

First Posted:

Nov 12, 2021

Last Update Posted:

Jul 11, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Judy Cho, Dean of Translational Genetics, Director, The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai

Inflammatory Bowel Disease

Non European Ancestry

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 11, 2022