Investigating the Anti-Human Immunodeficiency Virus (HIV) & Anti-inflammatory Effect of Chloroquine

Sponsor
University of Minnesota (Other)
Overall Status
Terminated
CT.gov ID
NCT00308620
Collaborator
Minnesota Medical Foundation (Other)
13
1
2
39
0.3

Study Details

Study Description

Brief Summary

Summary: Chloroquine is a medication that in laboratory settings has significant anti-HIV effects in HIV infected T-cells. Chloroquine has been used safely for over 60 years for malaria treatment and prevention, and it also has significant anti-inflammatory effects. No formal study of chloroquine has been performed in people with HIV infection. Chloroquine is used worldwide and is quite inexpensive outside of the United States. If shown to be effective, chloroquine could be a very important tool worldwide in delaying HIV disease progression which would extend the time period without needing anti-retroviral therapy. In countries where anti-retroviral therapy is not available, this could be very helpful.

This is an 8 week trial study requiring 3 study visits. Participants will be ask to take a once a day study medication (chloroquine or placebo) for 8 weeks and have three blood draws for CD4 counts, HIV viral loads, and other research tests. The visits are at study enrollment, 4 weeks, and 8 weeks.

Condition or Disease Intervention/Treatment Phase
  • Drug: chloroquine phosphate
  • Drug: Placebo
Phase 2/Phase 3

Detailed Description

Summary:

A phase I randomized, double-blind, placebo controlled trial to investigate the efficacy of chloroquine to decrease T-cell activation and decrease viral load in early HIV.

Scientific Rationale:

Chloroquine has in vivo direct anti-HIV effects and an anti-inflammatory effect. These properties may be beneficial in reducing viral burden and immune activation therefore delaying HIV disease progression.

Sample Size: 25

Length of Study: 8 weeks, [enrollment + 2 follow up visits].

Intervention:
  • Arm 1a: Chloroquine 250mg orally once daily for 8 weeks.

  • Arm 1b: Chloroquine 500mg orally once daily for 8 weeks.

  • Arm 2: Placebo once daily for 8 weeks.

Measurements:
  • Blood draws at weeks: 0, 4, and 8 weeks.

  • CD4, viral load measurements will be communicated to the referring provider (with subject consent).

Study Design

Study Type:
Interventional
Actual Enrollment :
13 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Pilot Study of the Anti-Viral and Anti-Inflammatory Effects of Chloroquine in Early HIV Infection
Study Start Date :
Mar 1, 2006
Actual Primary Completion Date :
Dec 1, 2008
Actual Study Completion Date :
Jun 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Chloroquine

Chloroquine 205mg or 500mg orally once daily (Results pooled)

Drug: chloroquine phosphate
250mg or 500mg PO (by mouth) QDay
Other Names:
  • Aralen
  • Placebo Comparator: Placebo

    Placebo once daily for 8 weeks

    Drug: Placebo
    Placebo once daily for 8 weeks

    Outcome Measures

    Primary Outcome Measures

    1. HIV Viral Load Change [baseline and 8 weeks]

      HIV-1 viral load change between baseline and 8 weeks

    Secondary Outcome Measures

    1. Change in Immune Activation Assessed by Flow Cytometry Analysis From Baseline to 8 Weeks [8 weeks]

      The Change in the percentages of CD38+ HLA-DR+ CD8 and CD4 memory T cells from baseline to 8 weeks.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • HIV-1 infected adults

    • CD4 count > 250 cells/mm3

    • Not presently receiving HIV antiretroviral therapy (> 6 months or naïve)

    • Viral load > 3000 RNA copies/mL (3.5 log)

    • No planned HIV anti-retroviral therapy for 8 weeks

    Exclusion Criteria:
    • Prior retinal eye disease

    • CD4 < 250 cells/µL

    • Renal failure

    • Active malignancy

    • Corticosteroid therapy

    • Age < 18 or > 65 years

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Minnesota ACTU Minneapolis Minnesota United States 55455

    Sponsors and Collaborators

    • University of Minnesota
    • Minnesota Medical Foundation

    Investigators

    • Principal Investigator: David R Boulware, MD, MPH, University of Minnesota

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00308620
    Other Study ID Numbers:
    • 0510M77007
    First Posted:
    Mar 29, 2006
    Last Update Posted:
    Jun 4, 2020
    Last Verified:
    Jun 1, 2020

    Study Results

    Participant Flow

    Recruitment Details 2006-2008 recruitment of volunteers in HIV care but electing to not receive ART.
    Pre-assignment Detail
    Arm/Group Title Chloroquine 500mg Placebo Chloroquine 250mg
    Arm/Group Description Chloroquine 500mg PO once daily x 8 weeks Placebo once daily for 8 weeks Chloroquine 250mg PO once daily x 8 weeks
    Period Title: Overall Study
    STARTED 3 4 6
    COMPLETED 2 3 5
    NOT COMPLETED 1 1 1

    Baseline Characteristics

    Arm/Group Title Chloroquine 500mg Placebo Chloroquine 250mg Total
    Arm/Group Description Chloroquine 500mg PO once daily x 8 weeks Placebo once daily for 8 weeks Chloroquine 250mg PO once daily x 8 weeks Total of all reporting groups
    Overall Participants 3 4 6 13
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    100%
    4
    100%
    6
    100%
    13
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    40
    (15)
    34
    (5)
    36
    (5)
    36.5
    (8.0)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    1
    25%
    0
    0%
    1
    7.7%
    Male
    3
    100%
    3
    75%
    6
    100%
    12
    92.3%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    4
    100%
    6
    100%
    13
    100%

    Outcome Measures

    1. Primary Outcome
    Title HIV Viral Load Change
    Description HIV-1 viral load change between baseline and 8 weeks
    Time Frame baseline and 8 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Chloroquine 250mg or 500mg Placebo
    Arm/Group Description Chloroquine 250mg or 500mg orally once daily x 8 weeks. n=6 for 250mg; n=3 for 500mg Placebo orally once daily for 8 weeks
    Measure Participants 9 4
    Log Mean (Standard Deviation) [log10 copies/mL]
    -.083
    (.5)
    0.0
    (.1)
    2. Secondary Outcome
    Title Change in Immune Activation Assessed by Flow Cytometry Analysis From Baseline to 8 Weeks
    Description The Change in the percentages of CD38+ HLA-DR+ CD8 and CD4 memory T cells from baseline to 8 weeks.
    Time Frame 8 weeks

    Outcome Measure Data

    Analysis Population Description
    Analysis of Chloroquine arms is pooled.
    Arm/Group Title Chloroquine 250mg or 500mg Placebo
    Arm/Group Description Chloroquine 500mg orally once daily x 8 weeks Placebo orally once daily for 8 weeks
    Measure Participants 7 3
    CD8 CD38+HLA-DR+
    -2.5
    1.85
    CD4 ki67+
    -2.0
    1.4

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Chloroquine 500mg Placebo Chloroquine 250mg
    Arm/Group Description Chloroquine 500mg PO once daily x 8 weeks Placebo once daily for 8 weeks Chloroquine 250mg PO once daily x 8 weeks
    All Cause Mortality
    Chloroquine 500mg Placebo Chloroquine 250mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Chloroquine 500mg Placebo Chloroquine 250mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 1/4 (25%) 0/6 (0%)
    Social circumstances
    Death (non-related) 1/3 (33.3%) 1 1/4 (25%) 1 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Chloroquine 500mg Placebo Chloroquine 250mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/4 (0%) 0/6 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title David Boulware
    Organization University of Minnesota
    Phone 6126269546
    Email boulw001@umn.edu
    Responsible Party:
    University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00308620
    Other Study ID Numbers:
    • 0510M77007
    First Posted:
    Mar 29, 2006
    Last Update Posted:
    Jun 4, 2020
    Last Verified:
    Jun 1, 2020