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Chloroquine as a Modulator of T Cell Immune Activation

This study has been completed.
Sponsor:
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
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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
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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
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, Quebec
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 Center
  More Information

Additional Information:
No publications provided

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
Health Authority: Canada: Canadian Institutes of Health Research

Keywords provided by CIHR Canadian HIV Trials Network:
Chloroquine
T cell immune activation
CD4 recovery
HIV

Additional relevant MeSH terms:
Chloroquine
Chloroquine diphosphate
Amebicides
Analgesics
Analgesics, Non-Narcotic
Anthelmintics
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimalarials
Antinematodal Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Central Nervous System Agents
Filaricides
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014