Clinical trial NCT05119140: Administration of Hydroxychloroquine (Plaquenil) to African Americans and Hispanics for the Treatment of Mild to Severe Ulcerative Colitis
Official title: Administration of Hydroxychloroquine (Plaquenil) to African Americans and Hispanics for the Treatment of Mild to Severe Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Ulcerative Colitis (Disorder)
Keywords: Ulcerative Colitis
Plaquenil
Hydroxychloroquine
CTLA-4
Inflammatory Bowel Disease
Non European Ancestry
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
First posted: 2021-11-12
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an Open Label study with blinded scorer for endoscopy and pathology reports.
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in surface CTLA4 expression
timeFrame: baseline and 4 months
Secondary outcomes:
measure: Change in Endoscopy Mayo Score
timeFrame: baseline and 4 months
measure: Change in Partial Mayo Score
timeFrame: baseline and 4 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai/Mount Sinai Hospital
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Judy H Cho, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Subra Kugathasan, MD
role: PRINCIPAL_INVESTIGATOR
References: