Chloroquine as a Modulator of T Cell Immune Activation

NCT02004314 | Completed DMC

• 1 other identifier: CTN 246
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV

Keywords

Chloroquine; T cell immune activation; CD4 recovery; HIV

Outcome Measures

Primary Outcomes (1)

• The expression of CD38 on CD8 circulating T cells

  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 Outcomes (1)

• 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

Study Arms (1)

Chloroquine

OTHER

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

Interventions

Chloroquine DRUG

Chloroquine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CIHR Canadian HIV Trials Network: lead

Study Sites (1)

Montreal Chest Institute, McGill University Health Centre

Montreal, Quebec, H3A1A1, Canada

Location

Related Publications (1)

• Routy JP, Angel JB, Patel M, Kanagaratham C, Radzioch D, Kema I, Gilmore N, Ancuta P, Singer J, Jenabian MA. Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV-infected patients receiving antiretroviral therapy. HIV Med. 2015 Jan;16(1):48-56. doi: 10.1111/hiv.12171. Epub 2014 Jun 2.

  PMID: 24889179 DERIVED

MeSH Terms

Interventions

Chloroquine

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jean-Pierre Routy, MD.

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2013
• First Posted: December 9, 2013
• Study Start: October 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: March 1, 2012
• Last Updated: December 9, 2013

Record last verified: 2013-12

Locations

CA (1)