Clinical Trials

MainTitle

Chloroquine as a Modulator of T Cell Immune Activation

This study has been completed
Sponsor
CIHR Canadian HIV Trials Network


Information provided by (Responsible Party)
CIHR Canadian HIV Trials Network
ClinicalTrials.gov Identifier
NCT02004314

First received: November 27, 2013
Last updated: December 3, 2013
Last Verified: December 2013
History of Changes
Purpose

Purpose

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.

Condition Intervention
HIV

Drug : Chloroquine

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by CIHR Canadian HIV Trials Network:

Primary Outcome Measures

  • 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.
Secondary Outcome Measures:
  • 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

Enrollment: 19
Study Start Date: October 2009
Study Completion Date: March 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 65 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02004314

Locations

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

Sponsors and Collaborators

CIHR Canadian HIV Trials Network

Investigators

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

More Information


Responsible Party: CIHR Canadian HIV Trials Network  
ClinicalTrials.gov Identifier: NCT02004314   History of Changes  
Other Study ID Numbers: CTN 246  
Study First Received: November 27, 2013  
Last Updated: December 3, 2013  

Keywords provided by CIHR Canadian HIV Trials Network:

Chloroquine
T cell immune activation
CD4 recovery
HIV

Additional relevant MeSH terms:
Chloroquine

ClinicalTrials.gov processed this data on July 10, 2020
This information is provided by ClinicalTrials.gov.