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Chloroquine for Reducing Immune Activation in HIV- Infected Individuals
This study is currently recruiting participants.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), August 2009
First Received: January 8, 2009   Last Updated: February 4, 2010   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00819390
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Chloroquine
Drug: Placebo
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Crossover Assignment
Official Title: A Phase II, Double Blind, Randomized, Exploratory Study of Chloroquine for Reducing HIV-Associated Immune Activation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Number of CD38 molecules per cell on CD8 T lymphocytes minus the number of CD38 molecules per cell on CD8 T lymphocytes at baseline [ Time Frame: At Baseline and Week 10 or Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of CD38 molecules per cell on CD8 T lymphocytes at the end of the 12-week period in the given arm when chloroquine treatment is given minus the number of CD38 molecules per cell on CD8 T lymphocytes at the beginning of that same period [ Time Frame: Before and after start of treatment ] [ Designated as safety issue: No ]
  • Occurrence of a Grade 3 or higher event [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • RNA copies/mL at study entry and study Weeks 12 and 24 [ Time Frame: At Entry and at Weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Number of CD38 molecules per CD8 T lymphocytes at Week 24 minus the number of CD38 molecules per cell on CD8 T lymphocytes at study entry in Arm A [ Time Frame: At Entry and Week 24 ] [ Designated as safety issue: No ]
  • Total CD4 T cell count at Week 12 minus total CD4 T cell count at study entry [ Time Frame: At Entry and Week 12 ] [ Designated as safety issue: No ]
  • Number of CD38 molecules per CD8 T lymphocytes at Week 24 minus the number of CD38 molecules per cell on CD8 T lymphocytes at Week 12 in Arm A [ Time Frame: At Weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Proportion of CD3 CD8 T cells that express CD38 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Proportion of CD3 CD8 T cells that express CD38 and human leukocyte antigen (HLA) DR [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Proportion of CD3 CD4 T cells that express CD38 and HLA DR [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Bacterial 16s rDNA levels expressed as copies/mm^3 of plasma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • The number of CD38 molecules per cell on CD8 T lymphocytes at Week 28 minus the number of Cd38 molecules per cell on CD8 T lymphocytes at the latest evaluation prior to receiving active chloroquine [ Time Frame: At Week 28 and most prior evaluation ] [ Designated as safety issue: No ]
  • Fasting lipopolysaccharide LPS and bacterial 16s rDNA levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Activation levels of pDC and mDC [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • The profile of gene expression in white blood cells at scheduled timepoints [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2009
Estimated Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Participants will receive chloroquine from Day 0 through the Week 12 study visit. Participants will then change to placebo treatment until the Week 24 study visit.
Drug: Chloroquine
Taken orally, once daily, at a dose of 250 mg for 12 weeks.
Drug: Placebo
Taken orally, once daily for 12 weeks.
2: Experimental
Participants will receive a chloroquine placebo treatment from Day 0 through the Week 12 study visit. Participants will then begin treatment with chloroquine until the Week 24 study visit.
Drug: Chloroquine
Taken orally, once daily, at a dose of 250 mg for 12 weeks.
Drug: Placebo
Taken orally, once daily for 12 weeks.

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 is 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. This study will also look at how well chloroquine is tolerated and its safety in HIV- infected patients.

Participants in this study will be randomly assigned to one of two treatment arms:

Arm A: Participants will receive 12 weeks of chloroquine treatment followed by 12 weeks of placebo

Arm B: Participants will receive 12 weeks of placebo followed by 12 weeks of chloroquine

Study treatment will be given once a day for a full 24 weeks. There will be an additional 4 weeks of follow-up for purposes of safety. After treatment has started, participants will be asked to come to the clinic on Weeks 4, 10, 12, 16, 22, and 24. At each visit participants will receive enough study treatment to last until the next visit. Each visit will last between 30 and 60 minutes. At most visits participants will have a physical exam, answer questions about any medications they are taking and how they are feeling, and have blood drawn for safety to assess CD4/CD8 cell counts and viral load. Some additional blood will also be stored for immunology testing. At some visits participants will be asked questions about their medication and medical history, have pupils dilated, have a hearing test, and have an electrocardiogram (EKG). Some visits will require participants to arrive fasting. Pregnancy tests may also be conducted if the participant is able to become pregnant or if pregnancy is suspected.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV infected
  • 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 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
  • Viral load greater than or equal to 10,000 copies/mL obtained within 30 days prior to study entry
  • 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.
  • 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
  • Ability and willingness to provide informed consent

Exclusion Criteria:

  • 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/L, within 30 days prior to study entry
  • History of retinal disease
  • History of neoplasm other than 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
  • A hearing threshold more than 25 decibels at any frequency from 500 hertz up to 2,000 hertz or more than 40 decibels at any frequency from 3,000 hertz up to and including 4,000 hertz on screening pure-tone audiogram by air conduction testing
  • History of tinnitus 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00819390

Locations
United States, Alabama
Alabama Therapeutics CRS Recruiting
Birmingham, Alabama, United States, 35294-2050
Contact: Karen G. Savage     205-975-7925     kgsavage@uab.edu    
Principal Investigator: Victoria A. Johnson, MD            
United States, California
Ucsd, Avrc Crs Recruiting
San Diego, California, United States, 92103
Contact: Jill Kunkel     619-543-8080     jkunkel@ucsd.edu    
Principal Investigator: Constance A. Benson, MD            
UCLA Care Center Recruiting
Los Angeles, California, United States, 90035
Contact: Maricela Gonzalez     310-557-3798     mmgonzalez@mednet.ucla.edu    
United States, Colorado
University of Colorado Hospital CRS Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Mary Graham Ray, RN, MSN     303-724-0712     graham.ray@uchsc.edu    
Principal Investigator: Thomas B. Campbell, MD            
United States, District of Columbia
Georgetown University CRS (GU CRS) Recruiting
Washington, District of Columbia, United States, 20007
Contact: Abimael Lopez     202-687-7387     al374@georgetown.edu    
Principal Investigator: Princy N. Kumar, MD            
United States, Illinois
Northwestern University CRS Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Baiba Berzins, MPH     312-695-4994     Baiba@northwestern.edu    
Principal Investigator: Babafemi O. Taiwo, MD            
United States, Maryland
Johns Hopkins Adult AIDS CRS Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Ilene Wiggins, RN     410-614-2766     imp@jhmi.edu    
Principal Investigator: Charles Flexner, MD            
United States, New York
NY Univ. HIV/AIDS CRS Active, not recruiting
New York, New York, United States, 10016
Cornell CRS Recruiting
New York, New York, United States, 10011
Contact: Todd Stroberg, RN, BSN     212-746-7198     tstrober@med.cornell.edu    
Principal Investigator: Timothy J. Wilkin, MD            
United States, Ohio
MetroHealth CRS Not yet recruiting
Cleveland, Ohio, United States, 44109
Contact: Ann Conrad, RN, ACRN     216-778-5489     aconrad@metrohealth.org    
Principal Investigator: Robert C Kalayjian, MD            
Case CRS Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Baum, RN     216-844-2546     baum.jane@clevelandactu.org    
Principal Investigator: Michael M. Lederman, MD            
Univ. of Cincinnati CRS Not yet recruiting
Cincinnati, Ohio, United States, 45267
Contact: Tammy Mansfield, R.N., A.C.R.N.     1-513-584-8373     mansfitl@ucmail.uc.edu    
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joseph Quinn, RN     215-349-8092     joseph.quinn@uphs.upenn.edu    
Principal Investigator: Pablo Tebas, MD            
United States, Tennessee
Vanderbilt Therapeutics CRS Recruiting
Nashville, Tennessee, United States, 37203
Contact: Deborah Sutherland     615-467-0154 ext 109     deborah.sutherland@vanderbilt.edu    
Principal Investigator: David W Haas, MD            
Sponsors and Collaborators
  More Information

Additional Information:
Publications:
Responsible Party: DAIDS ( Rona Siskind )
Study ID Numbers: ACTG A5258
Study First Received: January 8, 2009
Last Updated: February 4, 2010
ClinicalTrials.gov Identifier: NCT00819390     History of Changes
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Antiprotozoal Agents
Slow Virus Diseases
Physiological Effects of Drugs
Infection
Antimalarials
Antiparasitic Agents
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Amebicides
Analgesics
Retroviridae Infections
Antinematodal Agents
RNA Virus Infections
Immune System Diseases
Filaricides
Acquired Immunodeficiency Syndrome
Chloroquine
Anthelmintics
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Analgesics, Non-Narcotic
Chloroquine diphosphate
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on February 08, 2010