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Elite Controller and ART-treated HIV+ Statin Versus ASA Treatment Intervention Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT02081638
First received: March 5, 2014
Last updated: October 16, 2014
Last verified: September 2014
  Purpose

Background:

- The immune system protects the body from infection. But it can also cause harm. For example, the clotting system makes blood clot and protects from bleeding. But blood clots are sometimes harmful. People with human immunodeficiency virus (HIV) infection have increased inflammation and clotting. This may increase their risk for diseases like stroke or heart attack. Researchers want to know how aspirin or HMG-CoA reductase inhibitors (so-called statin medications) affect the immune and clotting systems of people with HIV. Aspirin is a medicine to decrease clotting. Statins are medications given to lower cholesterol and decrease inflammation.

Objectives:

- To see how aspirin or statins change immune and clotting systems in people with HIV.

Eligibility:

- Adults 18 and older with HIV and a low viral load, not on aspirin or a statin medication. They must also have either: (1) never taken anti-HIV medications (ARVs), have a suppressed viral load, have stable CD4 counts, and never had an opportunistic infection; or (2) been taking ARVs for 5 continuous years and have a suppressed viral load for more than 3 years.

Design:

  • Participants will be screened with medical history, physical exam, and blood and lab tests.
  • Participants will repeat screening tests and have an MRI. An MRI is a way to visualize blood vessels in the neck and head. Participants will lie on a table that slides in and out of a cylinder surrounded by a magnetic field.
  • Participants will take either study drug once daily for 9 months.
  • Participants will have a blood procedure twice. Blood will be removed through a needle in one arm and circulated through a machine that removes white blood cells. The blood, minus white blood cells, is returned through a needle in the other arm.
  • All participants will be observed for 3 months before and after treatment.

Condition Intervention Phase
HIV Infection
Drug: Aspirin 81 mg daily
Drug: Atorvastatin 40 mg daily
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Elite Controller and ART-Treated HIV+ Statin Versus ASA Treatment Intervention Study

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The primary end point will be change of sCD14 from Month 3 to Month 12 in the two groups combined (EC and ART & lt; 50) [ Time Frame: When the last participant has completed all evaluations. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in soluble biomarkers (sCD14, IL-6, D-dimer, hsCRP, sCD163, sTF as well as other relevant markers of inflammation and coagulation) in EC and ART & lt; 50 groups treated with ASA or ATV, independently within each group and arm and wit... [ Time Frame: When the last participant has completed all evaluations ]
  • Changes in T cell activation (measured by HLA-DR/CD38 co- expression), monocyte immune activation (measured by activated monocyte subsets expressing either CD14++CD16+ and CD14varCD16+ and markers of activation, CCR5 and TF, and migration, CCR2 ... [ Time Frame: When the last participant has completed all evaluations. ]
  • Changes in MR imaging of carotids after 9 months of statin or ASA in each group and both groups combined. [ Time Frame: When the last participant has completed all evaluations. ]

Estimated Enrollment: 120
Study Start Date: December 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Elite Controller
40 HIV positive elite controllers. Twenty will be randomized to aspirin and 20 will be randomized to atorvastatin.
Drug: Aspirin 81 mg daily
81 mg tablet, daily
Drug: Atorvastatin 40 mg daily
40 mg tablet, daily. In subjects on certain antiretroviral medications, ATV dosing will be adjusted in accordance with DHHS guidelines .
Active Comparator: Treated Progressors (ART)
40 HIV positive, treated progressors. Twenty will berandomized to Aspirin and 20 will be randomized toatorvastatin.
Drug: Aspirin 81 mg daily
81 mg tablet, daily
Drug: Atorvastatin 40 mg daily
40 mg tablet, daily. In subjects on certain antiretroviral medications, ATV dosing will be adjusted in accordance with DHHS guidelines .

Detailed Description:

Despite dramatic improvements in mortality with antiretroviral therapy (ART), HIV-infected persons remain at risk of developing non-infectious complications, including cardiovascular, renal, and neurological disease. A small subset of the HIV-infected population achieve durable control of HIV virus in the absence of ART. These individuals, termed elite controllers (ECs), remain ART na(SqrRoot) ve, have stable CD4 T cell counts for many years and have no history of opportunistic infections. Despite the lack of AIDS complications, recent evidence suggests ECs may exhibit heightened immune activation that may contribute to a potentially increased risk for non-infectious complications, similar to successfully treated progressors.

In the current 2 group, randomized, open label trial, we intend to study the effects of a lipid lowering agent vs aspirin (ASA) on immune activation in HIV-1 infected participants. One group will consist of ECs who are HIV-1 infected, maintain HIV-RNA levels of less than the LLD of commercially available assays in the absence of ART, have no history of ART or opportunistic infections (OIs) and have stable CD4 T cell counts for greater than 5 years. The second group will enroll HIV-1 infected Treated Progressors (henceforth referred to as ART < 50) who have maintained HIV-RNA below the limit of detection in commercially available assays (< 40, < 48, or < 50 copies/mL) for greater than 3 years on ART (treatment duration greater than 5 years). The EC and ART < 50 groups will be matched for age and smoking status. Up to 2 months after the screening and enrollment visit, each group will enter a 3 month observation period (to establish baseline values for biomarkers/cellular markers). After 3 months, participants from each group will be randomized to either ASA, 81 mg PO daily, or atorvastatin (ATV), 40 mg (dose adjusted for subjects on antiretroviral regimens with significant interactions, and will be treated for 9 months, followed by 3 months of a wash out period (see Figure 1). The primary end point will be change of sCD14 after 9 months of study intervention from Month 3 to Month 12 in each treatment arm, with groups combined (EC and ART < 50). Secondary objectives will be to compare changes in soluble biomarkers (sCD14, IL-6, D-dimer, hsCRP, sTF, sCD163 and other relevad treatment arms (ASA vs statin and EC vs ART< 50 and with groups combined), to evaluate cardiovascular (CV) disease prevalence in EC vs ART< 50 and with groups combined), to evaluate cardiovascular (CV) disease prevalence in EC vs ART < 50 by MR imaging of carotids, to determine MR measurements and correlations with biomarkers and cellular activation markers, and to investigate changes in plasma viremia as measured by single copy assay over time.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

EC Arm

  1. Age greater than or equal to 18 years.
  2. Documented HIV-1 infection confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blot tests (will not be repeated if performed previously at NIH).
  3. Categorized as a long term non-progressor EC as defined by viral load less than the LLD of commercially available assays and clinical and laboratory criteria (no OIs, no ART, stable CD4 T cell counts for more than 5 years). Viral load blips are allowed as long as they are less than 500 copies/mL and flanked by viral load measurements less than limit of detection of the commercially available assay
  4. In women of childbearing potential, with no plans for pregnancy for the next 15 months and willing to use 2 investigator approved highly reliable methods of birth control consistently while on the study or in 3 month follow up.
  5. Willingness to have samples stored for future research.
  6. Not on a statin or ASA for the past 6 months.

ART < 50 Arm

  1. Age greater than or equal to 18 years.
  2. Documented HIV-1 infection confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blot tests.
  3. In women of childbearing potential, with no plans for pregnancy for the next 15 months and willing to use 2 investigator approved highly reliable methods of birth control consistently while on the study or in 3 month follow up.
  4. On continuous combination ART > 5 years.
  5. HIV RNA < 50 copies/mL (or less than 40 or less than 48 copies/mL, depending on the lower limit of detection of the assay used; transient periods of low level (< 300) detectable virus, blips, acceptable if isolated and followed by < 50 copies/mL values) > 3 years and current HIV-RNA less than the LLD of the commercially available assay used. Subject will be rescreened if HIV is detectable at screening visit.
  6. Willingness to have samples stored for future research.
  7. Not on a statin or ASA for the past 6 months.

EXCLUSION CRITERIA

  1. Diagnosis of cardiovascular disease or hypercholesterolemia (LDL cholesterol 190 mg/dL).
  2. Known hypersensitivity or allergy to ATV or ASA, including a history of myositis or rhabdomyolysis with statin or ASA use.
  3. Other contraindication for ASA or statin therapy (active liver disease, peptic ulcer disease, etc.).
  4. Women who are lactating, pregnant, or actively trying to become pregnant or considering pregnancy over the likely span of the study (including women of childbearing potential who are unwilling to use adequate contraception throughout the study).
  5. Any chronic inflammatory condition either requiring anti-inflammatory medication (systemic corticosteroids, daily NSAID use,immunomodulating medications) which may, in the opinion of the investigator, confound the interpretation of soluble inflammatory biomarkers. While on study, short term (less than 5 days) NSAID use will be allowed at the discretion of the investigator.
  6. Active drug use or alcohol abuse that, in the opinion of the investigator, may interfere with the ability of the subject to participate in the study or that may unacceptably increase the risk of the study intervention..
  7. Safety laboratory cut offs: coagulation (INR > 2 upper limit of normal [ULN], PLT< 75K), renal function (GFR< 60), liver function (ALT or Alkaline phosphatase or direct bilirubin > 2x ULN), aldolase < 1.5 ULN and anemia (Hg < 9 mg/dL).
  8. Antiretroviral therapy with tipranivir, elvitegravir, or any therapy which combines non-nucleoside reverse transcriptase inhibitors with protease inhibitors.
  9. Chronic hepatitis C co-infection
  10. If either MR or apheresis is contraindicated, subject may still participate without this procedure. In the case of missed apheresis, a 30 mL research blood draw will be substituted (see Appendices B and C).

    • If statin initiation is indicated per current guidelines, subject will be counseled to consult with their PMD. If the subject then chooses to take part in the study, we will provide their PMD with all pertinent lab results during the course of the study, if requested.

Co-enrollment Guidelines: Co-enrollment in other trials will be restricted, other than enrollment on observational studies. Study staff should be notified of co-enrollment as it may require the approval of the Investigator.

  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: NCT02081638

Contacts
Contact: Delmyra Turpin, R.N. (301) 435-7937 turpindb@mail.nih.gov
Contact: Irini Sereti, M.D. (301) 496-5533 isereti@niaid.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
United States, Minnesota
Hennipen County Medical Center Recruiting
Minneapolis, Minnesota, United States
Sponsors and Collaborators
Investigators
Principal Investigator: Irini Sereti, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT02081638     History of Changes
Other Study ID Numbers: 140039, 14-I-0039
Study First Received: March 5, 2014
Last Updated: October 16, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immune Activation

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Aspirin
Atorvastatin
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Anticholesteremic Agents
Antimetabolites
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents

ClinicalTrials.gov processed this record on November 24, 2014