HIV InfectionsPhase 2NCT00819390
Chloroquine for Reducing Immune Activation in HIV- Infected Individuals
A Phase 2 study testing Chloroquine in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 15 sites in United States.
Trial summary
HIV is characterized by frequent immune system activation. Early in the course of infection the body establishes an immune activation "set point" related to the amount of HIV in the blood stream. This set point affects the rate of CD4 cell loss. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Chloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 15 sitesUnited States
- Study dates
- Mar 2009to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infected
- Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
- Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained
- Female participants of reproductive potential must have a negative pregnancy test performed within 24 hours prior to study entry
- If engaging in sexual activity, female participants must use adequate forms of contraception while receiving study treatment and for 4 weeks after stopping the treatment. More information on this criterion can be found in the study protocol.
- Ability and willingness to provide informed consent
Show all 18Show fewer
- Additional Inclusion Criteria for Off-ART Participants:
- No antiretroviral therapy (ART) for at least 6 months prior to study entry and not likely to start within the 6 months after study entry
- CD4 cell count greater than or equal to 400 cells/mm3 at screening, obtained within 30 days prior to study entry
- For participants with previous ART use, documentation or recall of nadir CD4 cell count greater than or equal to 200 cells/mm3
- HIV-1 RNA viral load greater than or equal to 1,000 copies/mL obtained within 30 days prior to study entry
- No history of CDC category C AIDS-related opportunistic infections
- Karnofsky performance score greater than or equal to 70 within 30 days prior to study entry
- Additional Inclusion Criteria for On-ART Participants:
- Receiving ART, defined as a regimen that includes three or more antiretroviral medications, for at least 24 months prior to study entry
- Required documentation that all HIV-1 viral loads (at least two) were below 400 copies/mL. More information on this criterion can be found in the study protocol.
- Screening HIV-1 RNA <200 copies/mL within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
- CD4 cell count <350 cells/mm3 at screening, obtained within 30 days prior to study entry
Who cannot join
- Continuous use of certain specified medication for more than 3 days within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
- Use of chloroquine or hydroxychloroquine within 3 months prior to study entry
- Known history of hypersensitivity to 4-aminoquinoline compounds (such as chloroquine or hydroxychloroquine)
- Active drug or alcohol use or dependence that, in the opinion of the investigator would interfere with adherence to study requirements
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
- Renal insufficiency, defined as serum creatinine greater than 1.5 mg/dL, within 30 days prior to study entry
Show all 18Show fewer
- History of retinal disease (i.e. confirmed retinopathy by ophthalmologic examination)
- History of neoplasm, within 5 years prior to study entry, other than treated in situ carcinoma or basal-cell or localized squamous cell carcinoma of the skin
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency at screening
- History of porphyria
- History of psoriasis
- History of cirrhosis
- History of seizure disorder
- History of tinnitus (ear and/or head noise lasting more than 5 minutes that occurs more often than once per week) or history of sudden hearing loss
- History of myopathy
- History of cardiac conduction abnormality or cardiomyopathy. More information on this criterion can be found in the study protocol.
- Additional Exclusion Criteria for On-ART Participants:
- Plans to change ART regimen with the 6 months after study entry (change in ART regimen is only permitted if due to toxicity)
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
University of Colorado Hospital CRS (6101)
Aurora, Colorado, 80045
Johns Hopkins Adult AIDS CRS (201)
Baltimore, Maryland, 21205
Alabama Therapeutics CRS (5801)
Birmingham, Alabama, 35294
Massachusetts General Hospital ACTG CRS (101)
Boston, Massachusetts, 02114
Unc Aids Crs (3201)
Chapel Hill, North Carolina, 27514
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, 45267
Case CRS (2501)
Cleveland, Ohio, 44106
MetroHealth CRS (2503)
Cleveland, Ohio, 44109
Vanderbilt Therapeutics CRS (3652)
Nashville, Tennessee, 37204
Cornell CRS (7804)
New York, New York, 10011
Hosp. of the Univ. of Pennsylvania CRS (6201)
Philadelphia, Pennsylvania, 19104
Pittsburgh CRS (1001)
Pittsburgh, Pennsylvania, 15213
Ucsd, Avrc Crs (701)
San Diego, California, 92103
Washington University CRS (2101)
St Louis, Missouri, 63110
Georgetown University CRS (GU CRS) (1008)
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase II, Double Blind, Randomized, Exploratory Study of Chloroquine for Reducing HIV-Associated Immune Activation
HIV is characterized by frequent immune system activation. Early in the course of infection the body establishes an immune activation "set point" related to the amount of HIV in the blood stream. This set point affects the rate of CD4 cell loss. Without CD4 cells, or with very low levels of CD4 cells, the body cannot fight off illness. This is known as immunodeficiency. If left untreated HIV can lead to extreme immunodeficiency and AIDS.
Evidence suggests that by decreasing the rate of immune system activation, immune deficiency progression could be prevented. The purpose of this study is to learn how well chloroquine can reduce the level of immune activation and to test the safety and tolerance of chloroquine in people infected with HIV.
Read the detailed description
HIV is characterized by persistent immune system activation, and early in the course of infection the body establishes an immune activation "set point" related to the amount of HIV in the blood stream. This set point affects the rate of CD4 cell loss. Without CD4 cells, or with very low levels of CD4 cells, the body cannot fight off illness. This is known as immunodeficiency. If left untreated HIV can lead to extreme immunodeficiency and AIDS.
Immune system activation includes activating the CD8 cells. These cells attack body cells infected with viruses. Because of this, CD4 cells infected with HIV are frequently destroyed by CD8 cells. The purpose of this study is to learn how well chloroquine reduces the level of activation of CD8 cells in people infected with HIV. Increased activation of CD8 cells is thought to lead to a more severe path of disease in HIV infection.
The constant immune activation observed in HIV- infected patients has also been linked to higher levels of byproducts from certain naturally occurring bacteria found in the gut that are known to be immune stimulants. By decreasing the stimulation from these byproducts with chloroquine treatment, HIV disease may be slowed.
The purpose of this study was to learn how well chloroquine reduces the level of activation of CD8 cells and lowers the levels of bacteria byproducts in people infected with HIV, either off antiretroviral therapy (ART) (protocol version 1.0 dated December 17, 2008) or on-ART (protocol version 2.0 dated October 1, 2010). The off-ART (Arms A and B) and on-ART (Arms C and D) participants were enrolled during different time periods, and the study was designed to analyze the two study populations separately. This study also looked at how well chloroquine was tolerated and its safety in HIV- infected participants.
Off-ART participants in the study were randomized with equal probability to one of two treatment arms:
Arm A: Participants received 12 weeks of chloroquine treatment followed by 12 weeks of placebo
Arm B: Participants received 12 weeks of placebo followed by 12 weeks of chloroquine
On-ART participants in the study were randomized with equal probability to one of two treatment arms:
Arm C: Participants received 12 weeks of chloroquine treatment followed by 12 weeks of placebo
Arm D: Participants received 12 weeks of placebo followed by 12 weeks of chloroquine
Study treatment was given once a day for a full 24 weeks. There was an additional 4 weeks of follow-up for purposes of safety. After treatment has started, participants were asked to come to the clinic on Weeks 4, 10, 12, 16, 22, and 24. At each visit participants were given enough study treatment to last until the next visit. Each visit lasted between 30 and 60 minutes. At most visits, participants had a physical exam, answered questions about any medications they were taking and how they are feeling, and had blood drawn for safety to assess CD4/CD8 cell counts and viral load. Some additional blood were also stored for immunology testing. At some visits, participants were asked questions about their medication and medical history, had pupils dilated, had a hearing test, and had an electrocardiogram (EKG). Some visits required participants to arrive fasting. Pregnancy tests were also conducted if the participant is able to become pregnant or if pregnancy was suspected.
- Conditions
- HIV Infections
- Being tested
- Chloroquine, Placebo
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChloroquineDrug
Taken orally, once daily, at a dose of 250 mg for 12 weeks.
PlaceboDrug
Taken orally, once daily for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| A: Chloroquine then Placebo for Off-ART Participants | Experimental | Participants received chloroquine treatment from Day 0 through the Week 12 study visit and then began chloroquine placebo treatment until the Week 24 study visit. Receives: Drug: Chloroquine; Drug: Placebo |
| B: Placebo then Chloroquine for Off-ART Participants | Experimental | Participants received chloroquine placebo treatment from Day 0 through the Week 12 study visit and then began chloroquine treatment until the Week 24 study visit. Receives: Drug: Chloroquine; Drug: Placebo |
| C: Chloroquine then Placebo for On-ART Participants | Experimental | Participants received chloroquine treatment from Day 0 through the Week 12 study visit and then began chloroquine placebo treatment until the Week 24 study visit. Receives: Drug: Chloroquine; Drug: Placebo |
| D: Placebo then Chloroquine for On-ART Participants | Experimental | Participants received chloroquine placebo treatment from Day 0 through the Week 12 study visit and then began chloroquine treatment until the Week 24 study visit. Receives: Drug: Chloroquine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Percent CD8 HLA-DR+/CD38+ From Baseline to Week 12
The baseline percent CD8 HLA-DR+/CD38+ (mean of pre-entry and entry percent CD8 HLA-DR+/CD38+) was subtracted from the mean of week 10 and week 12 percent CD8 HLA-DR+/CD38+.
Measured: At pre-entry, entry, weeks 10 and 12
Secondary outcomes (28)
Change in Percent CD8 HLA-DR+/CD38+ From Start to End of the 12-week Chloroquine Treatment Period
For Arm A: Chloroquine then Placebo for off-ART participants and Arm C: Chloroquine then Placebo for on-ART participants, the baseline percent CD8 HLA-DR+/CD38+ (mean of pre-entry and entry percent CD8 HLA-DR+/CD38+) was subtracted from the mean of week 10 and week 12 percent CD8 HLA-DR+/CD38+. For Arm B: Placebo then Chloroquine for off-ART participants and Arm D: Placebo then Chloroquine for on-ART participants, the mean of week 10 and week 12 percent CD8 HLA-DR+/CD38+ was subtracted from the mean of week 22 and week 24 percent CD8 HLA-DR+/CD38+.
Measured: For Arms A and C: Pre-entry, entry, weeks 10 and 12. For Arms B and D: Weeks 10, 12, 22 and 24
Change in Percent CD8 HLA-DR+/CD38+ From Week 12 to Week 24
The mean of week 10 and week 12 percent CD8 HLA-DR+/CD38+ is subtracted from the mean of the week 22 and week 24 percent CD8 HLA-DR+/CD38+
Measured: At Weeks 10, 12, 22 and 24
Change in Percent CD8 HLA-DR+/CD38+ From Baseline to Week 24 in Arm A and Arm C
The baseline percent CD8 HLA-DR+/CD38+ (mean of pre-entry and entry percent CD8 HLA-DR+/CD38+) was subtracted from the mean of week 22 and week 24 percent CD8 HLA-DR+/CD38+.
Measured: At Pre-entry, entry, Weeks 22 and 24
Change in Total CD4 T Cell Count From Baseline to Week 12
Baseline CD4 count (mean of pre-entry and entry CD4 count) is subtracted from the mean of week 10 and week 12 CD4 count
Measured: At pre-entry, entry, weeks 10 and 12
Number of Participants With Events Grade 3 or Higher
Events included signs and symptoms, laboratory abnormalities and/or clinical events grade 3 or higher which were described by site clinician blinded to the treatment arm as definitely or possibly related to the study treatment.
Measured: From start of study treatment to study completion at week 28
HIV-1 RNA Copies/mL at Study Entry for Off-ART Participants
Results reported are for HIV-1 RNA (copies/mL) at study entry for off-ART participants.
Measured: At Entry
HIV-1 RNA Copies/mL at Weeks 12 and 24 for Off-ART Participants
Results reported are for HIV-1 RNA (copies/mL) at week 12 and week 24 for off-ART participants.
Measured: At weeks 12 and 24
HIV-1 RNA Copies/mL at Study Entry for On-ART Participants
Results reported are for HIV-1 RNA at study entry for on-ART participants.
Measured: At Entry
HIV-1 RNA Copies/mL at Week 12 for On-ART Participants
Results reported are for HIV-1 RNA at week 12 for on-ART participants.
Measured: At week 12
HIV-1 RNA Copies/mL at Week 24 for On-ART Participants
Results reported are for HIV-1 RNA at week 24 for on-ART participants.
Measured: At week 24
Percent CD8 CD38+ at Baseline
Baseline CD8 CD38+ is computed as the mean of pre-entry and entry CD8 CD38+.
Measured: At pre-entry and entry
Percent CD8 CD38+ at Week 12
Results reported are the week 12 percentage of CD8 expressing CD38+.
Measured: At Week 12
Percent CD8 CD38+ at Week 24
Results reported are the week 24 percentage of CD8 expressing CD38+.
Measured: At Week 24
Percent CD4 HLA-DR+/CD38+ at Baseline
Baseline CD4 HLA-DR+/CD38+ is computed as the mean of pre-entry and entry CD4 HLA-DR+/CD38+.
Measured: At pre-entry and entry
Percent CD4 HLA-DR+/CD38+ at Week 12
Results reported are the week 12 percentage of CD4 expressing HLA-DR+/CD38+.
Measured: At Week 12
Percent CD4 HLA-DR+/CD38+ at Week 24
Results reported are the week 24 percentage of CD4 expressing HLA-DR+/CD38+.
Measured: At Week 24
IL-6, Soluble TNF-rI (sTNF-rI) and D-dimer at Baseline
Baseline IL-6, sTNF-rI and D-dimer were computed as the mean of pre-entry and entry IL-6, sTNF-rI and D-dimer, respectively.
Measured: At pre-entry and entry
IL-6, Soluble TNF-rI (sTNF-rI) and D-dimer at Week 12
Results reported are the week 12 IL-6, sTNF-rI and D-dimer.
Measured: At week 12
IL-6, Soluble TNF-rI (sTNF-rI) and D-dimer at Week 24
Results reported are the week 24 IL-6, sTNF-rI and D-dimer.
Measured: At week 24
Soluble CD14 (sCD14) at Baseline
Baseline sCD14 was computed as the mean of pre-entry and entry sCD14.
Measured: At pre-entry and entry
Soluble CD14 (sCD14) at Week 12
Results reported are the week 12 sCD14.
Measured: At week 12
Soluble CD14 (sCD14) at Week 24
Results reported are the week 24 sCD14.
Measured: At week 24
Fasting Lipopolysaccharides (LPS) at Entry
Results reported are for entry fasting LPS.
Measured: At entry
Fasting Lipopolysaccharides (LPS) at Week 12
Results reported are the week 12 fasting LPS.
Measured: At week 12
Fasting Lipopolysaccharides (LPS) at Week 24
Results reported are the week 24 fasting LPS.
Measured: At week 24
Percent Activation Levels of Plasmacytoid Dendritic Cells (pDC) and Myeloid Dendritic Cells (mDC) at Baseline
Baseline percent activation levels of pDC were computed as the mean of pre-entry and entry percent activation levels of pDC. Similarly, baseline percent activation levels of mDC were computed as the mean of pre-entry and entry percent activation levels of mDC.
Measured: At pre-entry and entry
Percent Activation Levels of Plasmacytoid Dendritic Cells (pDC) and Myeloid Dendritic Cells (mDC) at Week 12
Results reported are the week 12 percent activation levels of pDC and mDC.
Measured: At week 12
Percent Activation Levels of Plasmacytoid Dendritic Cells (pDC) and Myeloid Dendritic Cells (mDC) at Week 24
Results reported are the week 24 percent activation levels of pDC and mDC.
Measured: At week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2009 (estimated)
- Study startMar 2009
- Primary completionFeb 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Jeffrey M Jacobson, MD, Study chair, Drexel University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00819390
- Sponsor's protocol ID
- ACTG A5258
- Other IDs
- 1U01AI068636
- Status last verified
- Oct 2014
- First submitted
- 8 Jan 2009
- Last updated
- 13 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Neely M, Kalyesubula I, Bagenda D, Myers C, Olness K. Effect of chloroquine on human immunodeficiency virus (HIV) vertical transmission. Afr Health Sci. 2003 Aug;3(2):61-7.
PubMed 12913796Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003 Nov;3(11):722-7. doi: 10.1016/s1473-3099(03)00806-5.
PubMed 14592603Semrau K, Kuhn L, Kasonde P, Sinkala M, Kankasa C, Shutes E, Vwalika C, Ghosh M, Aldrovandi G, Thea DM. Impact of chloroquine on viral load in breast milk. Trop Med Int Health. 2006 Jun;11(6):800-3. doi: 10.1111/j.1365-3156.2006.01645.x.
PubMed 16772000Jacobson JM, Bosinger SE, Kang M, Belaunzaran-Zamudio P, Matining RM, Wilson CC, Flexner C, Clagett B, Plants J, Read S, Purdue L, Myers L, Boone L, Tebas P, Kumar P, Clifford D, Douek D, Silvestri G, Landay AL, Lederman MM. The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1. AIDS Res Hum Retroviruses. 2016 Jul;32(7):636-47. doi: 10.1089/AID.2015.0336. Epub 2016 Apr 19.
PubMed 26935044
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Double Blind, Randomized, Exploratory Study of Chloroquine for Reducing HIV-Associated Immune Activation
- ClinicalTrials.gov ID
- NCT00819390
- Acronym / sponsor ID
- ACTG A5258
- Conditions
- HIV Infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Mar 2009
- Primary completion
- Feb 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 9 Jan 2009 (estimated)
- Results
- Posted 5 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HIV is characterized by frequent immune system activation. Early in the course of infection the body establishes an immune activation "set point" related to the amount of HIV in the blood stream. This set point affects the rate of CD4 cell loss. Without CD4 cells, or with very low levels of CD4 cells, the body cannot fight off illness. This is known as immunodeficiency. If left untreated HIV can lead to extreme immunodeficiency and AIDS.
Evidence suggests that by decreasing the rate of immune system activation, immune deficiency progression could be prevented. The purpose of this study is to learn how well chloroquine can reduce the level of immune activation and to test the safety and tolerance of chloroquine in people infected with HIV.
Detailed description
HIV is characterized by persistent immune system activation, and early in the course of infection the body establishes an immune activation "set point" related to the amount of HIV in the blood stream. This set point affects the rate of CD4 cell loss. Without CD4 cells, or with very low levels of CD4 cells, the body cannot fight off illness. This is known as immunodeficiency. If left untreated HIV can lead to extreme immunodeficiency and AIDS.
Immune system activation includes activating the CD8 cells. These cells attack body cells infected with viruses. Because of this, CD4 cells infected with HIV are frequently destroyed by CD8 cells. The purpose of this study is to learn how well chloroquine reduces the level of activation of CD8 cells in people infected with HIV. Increased activation of CD8 cells is thought to lead to a more severe path of disease in HIV infection.
The constant immune activation observed in HIV- infected patients has also been linked to higher levels of byproducts from certain naturally occurring bacteria found in the gut that are known to be immune stimulants. By decreasing the stimulation from these byproducts with chloroquine treatment, HIV disease may be slowed.
The purpose of this study was to learn how well chloroquine reduces the level of activation of CD8 cells and lowers the levels of bacteria byproducts in people infected with HIV, either off antiretroviral therapy (ART) (protocol version 1.0 dated December 17, 2008) or on-ART (protocol version 2.0 dated October 1, 2010). The off-ART (Arms A and B) and on-ART (Arms C and D) participants were enrolled during different time periods, and the study was designed to analyze the two study populations separately. This study also looked at how well chloroquine was tolerated and its safety in HIV- infected participants.
Off-ART participants in the study were randomized with equal probability to one of two treatment arms:
Arm A: Participants received 12 weeks of chloroquine treatment followed by 12 weeks of placebo
Arm B: Participants received 12 weeks of placebo followed by 12 weeks of chloroquine
On-ART participants in the study were randomized with equal probability to one of two treatment arms:
Arm C: Participants received 12 weeks of chloroquine treatment followed by 12 weeks of placebo
Arm D: Participants received 12 weeks of placebo followed by 12 weeks of chloroquine
Study treatment was given once a day for a full 24 weeks. There was an additional 4 weeks of follow-up for purposes of safety. After treatment has started, participants were asked to come to the clinic on Weeks 4, 10, 12, 16, 22, and 24. At each visit participants were given enough study treatment to last until the next visit. Each visit lasted between 30 and 60 minutes. At most visits, participants had a physical exam, answered questions about any medications they were taking and how they are feeling, and had blood drawn for safety to assess CD4/CD8 cell counts and viral load. Some additional blood were also stored for immunology testing. At some visits, participants were asked questions about their medication and medical history, had pupils dilated, had a hearing test, and had an electrocardiogram (EKG). Some visits required participants to arrive fasting. Pregnancy tests were also conducted if the participant is able to become pregnant or if pregnancy was suspected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| A: Chloroquine then Placebo for Off-ART Participants | Experimental | Drug: Chloroquine, Drug: PlaceboParticipants received chloroquine treatment from Day 0 through the Week 12 study visit and then began chloroquine placebo treatment until the Week 24 study visit. |
| B: Placebo then Chloroquine for Off-ART Participants | Experimental | Drug: Chloroquine, Drug: PlaceboParticipants received chloroquine placebo treatment from Day 0 through the Week 12 study visit and then began chloroquine treatment until the Week 24 study visit. |
| C: Chloroquine then Placebo for On-ART Participants | Experimental | Drug: Chloroquine, Drug: PlaceboParticipants received chloroquine treatment from Day 0 through the Week 12 study visit and then began chloroquine placebo treatment until the Week 24 study visit. |
| D: Placebo then Chloroquine for On-ART Participants | Experimental | Drug: Chloroquine, Drug: PlaceboParticipants received chloroquine placebo treatment from Day 0 through the Week 12 study visit and then began chloroquine treatment until the Week 24 study visit. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- HIV-1 infected
- Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
- Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained
- Female participants of reproductive potential must have a negative pregnancy test performed within 24 hours prior to study entry
- If engaging in sexual activity, female participants must use adequate forms of contraception while receiving study treatment and for 4 weeks after stopping the treatment. More information on this criterion can be found in the study protocol.
Key exclusion criteria (18 listed)
- Continuous use of certain specified medication for more than 3 days within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
- Use of chloroquine or hydroxychloroquine within 3 months prior to study entry
- Known history of hypersensitivity to 4-aminoquinoline compounds (such as chloroquine or hydroxychloroquine)
- Active drug or alcohol use or dependence that, in the opinion of the investigator would interfere with adherence to study requirements
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChloroquineTaken orally, once daily, at a dose of 250 mg for 12 weeks. | Drug | A: Chloroquine then Placebo for Off-ART Participants, B: Placebo then Chloroquine for Off-ART Participants, C: Chloroquine then Placebo for On-ART Participants, D: Placebo then Chloroquine for On-ART Participants |
| PlaceboTaken orally, once daily for 12 weeks. | Drug | A: Chloroquine then Placebo for Off-ART Participants, B: Placebo then Chloroquine for Off-ART Participants, C: Chloroquine then Placebo for On-ART Participants, D: Placebo then Chloroquine for On-ART Participants |
Primary outcome
Change in Percent CD8 HLA-DR+/CD38+ From Baseline to Week 12
Time frame: At pre-entry, entry, weeks 10 and 12
The baseline percent CD8 HLA-DR+/CD38+ (mean of pre-entry and entry percent CD8 HLA-DR+/CD38+) was subtracted from the mean of week 10 and week 12 percent CD8 HLA-DR+/CD38+.
28 secondary outcomes
Change in Percent CD8 HLA-DR+/CD38+ From Start to End of the 12-week Chloroquine Treatment Period
Time frame: For Arms A and C: Pre-entry, entry, weeks 10 and 12. For Arms B and D: Weeks 10, 12, 22 and 24
Change in Percent CD8 HLA-DR+/CD38+ From Week 12 to Week 24
Time frame: At Weeks 10, 12, 22 and 24
Change in Percent CD8 HLA-DR+/CD38+ From Baseline to Week 24 in Arm A and Arm C
Time frame: At Pre-entry, entry, Weeks 22 and 24
Change in Total CD4 T Cell Count From Baseline to Week 12
Time frame: At pre-entry, entry, weeks 10 and 12
Number of Participants With Events Grade 3 or Higher
Time frame: From start of study treatment to study completion at week 28
HIV-1 RNA Copies/mL at Study Entry for Off-ART Participants
Time frame: At Entry
HIV-1 RNA Copies/mL at Weeks 12 and 24 for Off-ART Participants
Time frame: At weeks 12 and 24
HIV-1 RNA Copies/mL at Study Entry for On-ART Participants
Time frame: At Entry
HIV-1 RNA Copies/mL at Week 12 for On-ART Participants
Time frame: At week 12
HIV-1 RNA Copies/mL at Week 24 for On-ART Participants
Time frame: At week 24
Percent CD8 CD38+ at Baseline
Time frame: At pre-entry and entry
Percent CD8 CD38+ at Week 12
Time frame: At Week 12
Percent CD8 CD38+ at Week 24
Time frame: At Week 24
Percent CD4 HLA-DR+/CD38+ at Baseline
Time frame: At pre-entry and entry
Percent CD4 HLA-DR+/CD38+ at Week 12
Time frame: At Week 12
Percent CD4 HLA-DR+/CD38+ at Week 24
Time frame: At Week 24
IL-6, Soluble TNF-rI (sTNF-rI) and D-dimer at Baseline
Time frame: At pre-entry and entry
IL-6, Soluble TNF-rI (sTNF-rI) and D-dimer at Week 12
Time frame: At week 12
IL-6, Soluble TNF-rI (sTNF-rI) and D-dimer at Week 24
Time frame: At week 24
Soluble CD14 (sCD14) at Baseline
Time frame: At pre-entry and entry
Soluble CD14 (sCD14) at Week 12
Time frame: At week 12
Soluble CD14 (sCD14) at Week 24
Time frame: At week 24
Fasting Lipopolysaccharides (LPS) at Entry
Time frame: At entry
Fasting Lipopolysaccharides (LPS) at Week 12
Time frame: At week 12
Fasting Lipopolysaccharides (LPS) at Week 24
Time frame: At week 24
Percent Activation Levels of Plasmacytoid Dendritic Cells (pDC) and Myeloid Dendritic Cells (mDC) at Baseline
Time frame: At pre-entry and entry
Percent Activation Levels of Plasmacytoid Dendritic Cells (pDC) and Myeloid Dendritic Cells (mDC) at Week 12
Time frame: At week 12
Percent Activation Levels of Plasmacytoid Dendritic Cells (pDC) and Myeloid Dendritic Cells (mDC) at Week 24
Time frame: At week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12913796Neely M, Kalyesubula I, Bagenda D, Myers C, Olness K. Effect of chloroquine on human immunodeficiency virus (HIV) vertical transmission. Afr Health Sci. 2003 Aug;3(2):61-7.
- Background: PubMed 14592603Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003 Nov;3(11):722-7. doi: 10.1016/s1473-3099(03)00806-5.
- Background: PubMed 16772000Semrau K, Kuhn L, Kasonde P, Sinkala M, Kankasa C, Shutes E, Vwalika C, Ghosh M, Aldrovandi G, Thea DM. Impact of chloroquine on viral load in breast milk. Trop Med Int Health. 2006 Jun;11(6):800-3. doi: 10.1111/j.1365-3156.2006.01645.x.
- Derived from this study: PubMed 26935044Jacobson JM, Bosinger SE, Kang M, Belaunzaran-Zamudio P, Matining RM, Wilson CC, Flexner C, Clagett B, Plants J, Read S, Purdue L, Myers L, Boone L, Tebas P, Kumar P, Clifford D, Douek D, Silvestri G, Landay AL, Lederman MM. The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1. AIDS Res Hum Retroviruses. 2016 Jul;32(7):636-47. doi: 10.1089/AID.2015.0336. Epub 2016 Apr 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey M Jacobson, MD study chair
Drexel University College of Medicine
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chloroquine in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Percent CD8 HLA-DR+/CD38+ From Baseline to Week 12 (time frame: At pre-entry, entry, weeks 10 and 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00819390, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2014.