Chloroquine as a Modulator of T Cell Immune Activation

December 3, 2013 updated by: CIHR Canadian HIV Trials Network

Chloroquine as a Modulator of T Cell Immune Activation to Improve CD4 Recovery in HIV-infected Participants Receiving Antiretroviral Therapy: A Proof-of-concept Study

This study will evaluate the effect of chloroquine in individuals infected with HIV. Researchers will aim to determine if chloroquine treatment in participants whose viral loads are suppressed on combination antiretroviral therapy (ART), results in improved immune activation and CD4 cell recovery.

The study will recruit 20 individuals and will last approximately 44 weeks. Eligible participants will receive an oral dose of chloroquine (250 mg) once daily from week 8 through week 32. All participants will be asked to have rectal biopsy samples (week 0 and week 32) to study T cell immune activation in the mucosa rectal site.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Clinical data has identified chloroquine as a potential modulator of immune activation. The study's dose of chloroquine is the same as the dose recommended for patients having autoimmune diseases. In these autoimmune cases, a daily dose of chloroquine at 250 mg for 12 weeks has shown improvement in symptoms and decreases in inflammatory cytokines synthesis and a reduction in TLR -mediated immune activation. Study findings could help provide information about where and under what circumstances chloroquine treatment may reduce T cell activation and help restore circulating CD4 T cells.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3A1A1
        • Montreal Chest Institute, McGill University Health Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Documented HIV infection by Western Blot, EIA assays or viral load assay.
  • Aged between 18 and 65 years.
  • Viral load less than 50 copies per ml for at least the previous 36 weeks.
  • CD4 cell count less than or equal to 350 cells per litre.
  • On stable ART
  • Vital signs, physical examination and laboratory results do not exhibit evidence diseases such as advanced cirrhosis or advanced liver
  • Karnofsky performance status greater than or equal to 80 per cent.
  • Participant does not require and agrees not to take, for the duration of the study, any medication that is contraindicated with chloroquine.
  • Able to give informed consent.

Exclusion Criteria:

  • Active AIDS events in the last 3 months
  • Co-infection with active hepatitis B or C virus.
  • Current use or use within four weeks prior to the baseline visit, of cytotoxic agents, systemic corticosteroids or any immuno-modulatory agents.
  • Current use within four weeks prior to the chloroquine therapy the following medications: methadone, chlorpromazine, cimetidine, cyclosporin, methotrexate and penicillanime.
  • Psychiatric or cognitive disturbance or illness that could preclude compliance with the study.
  • Patient with clinically significant hemophilia and Von-Willebrand disease and any severe bleeding disorder.
  • Experimental HIV immune based therapy within 6 months of screening visit.
  • Allergic reaction to chloroquine.
  • A history of retinitis or any retinal problem.
  • Subjects with G6PD deficiency, porphyria, psoriasis, cirrhosis, hearing deficiency (including tinnitus), myopathy and cardiomyopathy.
  • Pregnant and breast-feeding women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Chloroquine
This will be a single arm, pilot study with each subject as his/her own control. The study will last 44 weeks, with 8 weeks observation period on ART alone to assess stability of activated CD8CD38 T cells, followed by 24 weeks chloroquine treatment with ART and a 12-week follow-up period on ART alone. Twenty ART treated patients will be recruited. To maximize chances of demonstrating a treatment effect, the chloroquine will be administrated for 24 weeks.
Drug: Chloroquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The expression of CD38 on CD8 circulating T cells
Time Frame: 44 weeks, with 8 weeks observation period on ART alone to assess stability of activated CD8CD38 T cells, followed by 24 weeks chloroquine treatment with ART and a 12-week follow-up period on ART alone
To assess whether the expression of CD38 on CD8 circulating T cells will be reduced and whether circulating CD4 T cell recovery will be enhanced after 24 weeks of chloroquine treatment in adults whose HIV replication is suppressed by ART.
44 weeks, with 8 weeks observation period on ART alone to assess stability of activated CD8CD38 T cells, followed by 24 weeks chloroquine treatment with ART and a 12-week follow-up period on ART alone

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of chloroquine treatment measured by adverse events, hematology and serum chemistries and Amsler grid test.
Time Frame: 44 weeks, with 8 weeks observation period on ART alone to assess stability of activated CD8CD38 T cells, followed by 24 weeks chloroquine treatment with ART and a 12-week follow-up period on ART alone
Safety of chloroquine treatment measured by adverse events, hematology and serum chemistries and Amsler grid test
44 weeks, with 8 weeks observation period on ART alone to assess stability of activated CD8CD38 T cells, followed by 24 weeks chloroquine treatment with ART and a 12-week follow-up period on ART alone

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CIHR Canadian HIV Trials Network

Investigators

  • Principal Investigator: Jean-Pierre Routy, MD., McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (ACTUAL)

January 1, 2012

Study Completion (ACTUAL)

March 1, 2012

Study Registration Dates

First Submitted

November 27, 2013

First Submitted That Met QC Criteria

December 3, 2013

First Posted (ESTIMATE)

December 9, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

December 9, 2013

Last Update Submitted That Met QC Criteria

December 3, 2013

Last Verified

December 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTN 246

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV

Clinical Trials on Chloroquine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Qatar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe