Atorvastatin on Biomarkers of Inflammation, Coagulopathy, Angiogenesis & T-cells

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Pfizer
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01351025
First received: November 8, 2010
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

Since people started taking HIV medications, illness from AIDS has decreased, but other serious diseases like heart disease (heart attacks) and certain kinds of cancer have increased. HIV causes inflammation (irritation) inside the body that cannot be felt but can be measured by levels of certain inflammation blood tests (blood tests that measure this irritation inside the body that you cannot feel). Inflammation may contribute to diseases (such as heart attacks) that have become some of the leading causes of death in people with HIV. HIV therapy can partially lower levels of inflammation measured in blood, however, levels of inflammation in people who have HIV who are taking certain kinds of anti-HIV drugs may remain high compared with those found in people not infected with HIV.

Atorvastatin is a drug approved by the Food and Drug Administration (FDA) for treating high cholesterol. Atorvastatin has also been able to lower the level of inflammation blood tests in certain other diseases but has not been studied for this purpose in people who have HIV. The main goal of this experimental study is to see how taking atorvastatin affects inflammation blood tests in people infected with HIV who do not need to take medicine for high cholesterol. In addition to observing the effects of atorvastatin on the level of inflammation measured in the blood, this study will see if atorvastatin is safe for people with HIV who are also taking medication for HIV.


Condition Intervention Phase
HIV-1 Infection
Drug: atorvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Study Evaluating the Effect of Atorvastatin on Biomarkers of Inflammation, Coagulopathy, Angiogenesis, and T-lymphocyte Activation in HIV-1 Infected Individuals With Suppressed HIV-1 RNA and LDL Cholesterol

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Interleukin 6 (IL-6) and D-dimer [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
  • CD4+ and CD8+ T-cell activation [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Atorvastatin effects on Hs-CRP, tissue factor, VEGF, MCP-1, and sCD14 [ Time Frame: 44 weeks ] [ Designated as safety issue: No ]
  • Atorvastatin safety, defined as Grade ≥ 2 signs and symptoms, > 3 x ULN AST or ALT, or Grade ≥ 2 laboratory abnormalities, in protease inhibitor treated, HIV -infected subjects [ Time Frame: 44 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 98
Study Start Date: December 2010
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
At week 0 participants will continue the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiate atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity are found, the dose of atorvastatin will be increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin will be stopped for a 4-week washout period. At week 24, placebo will be started for 4 weeks. If no symptoms or lab findings suggestive of toxicity are found, the placebo dose will be doubled at week 28. At week 44, the placebo will be stopped to allow for another 4-week washout period.
Drug: atorvastatin
10 mg daily for 4 weeks, if no symptoms or lab findings suggestive of atorvastatin toxicity, dose increase to 20 mg daily from week 4- week 20
Experimental: Arm B

At study entry (week 0), continue the entry-boosted PI-based antiretroviral regimen (not provided by the study) and initiate placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity are found, the dose of placebo will be doubled at the week 4 visit. At week 20, the placebo will be stopped for a 4-week washout period.

At week 24, atorvastatin will be started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity are found, the dose of atorvastatin will be increased to 20 mg daily at week 28. At week 44, atorvastatin will be stopped to allow for another 4-week washout period.

Drug: atorvastatin
Starting at week 24, 10 mg daily for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity are found, 20 mg daily from week 28- week 44.

  Eligibility

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

Inclusion Criteria:

  • HIV-1 infected
  • Combination ART that includes any boosted PI regimen for at least 6 months prior to study entry
  • No plans to change the antiretroviral regimen in the next year
  • Must be on the same HAART regimen for at least 12 weeks with no change prior to study entry. More information on this criterion can be found in the study protocol.
  • If on vitamin D replacement therapy, must be on stable regimen for ≥ 1 mo. prior to study entry.
  • CD4+ T-cell count obtained within 45 days prior to study entry at any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
  • Screening HIV-1 RNA < 40 copies/mL by Abbott RealTime PCR at a laboratory certified by the DAIDS Virology Quality Assurance (VQA) program within 45 days prior to study entry.
  • All known HIV-1 RNA levels obtained within 180 days prior to study entry are below the limits of quantification on all tests, with documentation of at least 1 test by any FDA-approved assay at a CLIA-certified laboratory obtained between 90 to 180 days prior to study entry. A single RNA "blip" of < 500 copies/mL during this time period is permissible if RNA levels immediately before and after are below the limits of quantification for the assay.
  • Laboratory values obtained within 45 days prior to study entry- Absolute neutrophil count (ANC) 750/mm3, Hemoglobin ≥ 9.0 g/dL for female subjects,10.0 g/dL for male subjects, Platelet count ≥ 100,000/mm3, Calculated creatinine clearance (CrCl) 30 mL/min, as estimated by the Cockcroft-Gault equation, Creatine kinase (CK) < 3 x ULN, AST ≤ 2.0 x ULN, ALT ≤ 2.0 x ULN, Total bilirubin ≤ 2.5 x ULN. If the subject if taking an indinavir- or atazanavir-containing regimen at the time of screening, a total bilirubin of ≤ 5 x ULN is acceptable, Fasting LDL cholesterol ≥ 70 mg/dL and < 130 mg/dL, Fasting triglycerides < 400 mg/dL, Fasting glucose < 110 mg/dL
  • Screening plasma D-dimer > 0.34 μg/mL from a sample obtained within 45 days prior to study entry.
  • For females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within 24 months prior to study entry), or women who have not undergone surgical sterilization, specifically hysterectomy or bilateral oophorectomy or tubal ligation) will require a negative serum or urine pregnancy test within 48 hours prior to entry. More information on this criterion can be found in the study protocol.
  • Must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least 2 reliable methods of contraception, (condoms, without a spermicidal agent; a diaphragm or cervical cap without spermicide; an IUD; or hormone-based contraceptive), for 2 weeks before study treatment, while receiving study treatment, and for 6 weeks after receiving study treatment. As hormone-based contraceptives (oral, transdermal, or subdermal) can affect coagulopathy biomarkers, subjects who plan on using such a contraceptive during the study must be taking the same product for ≥ 4 weeks prior to screening and be encouraged to continue throughout the duration of the study if medically feasible.
  • Karnofsky performance score ≥ 70 on at least one occasion within 45 days prior to study entry
  • Confirmation of the availability of the stored pre-entry fasting plasma, serum, and cell samples. The site must confirm that these samples have been entered into the Laboratory Data Management System (LDMS).

Exclusion Criteria:

  • Current or past malignancy (except non-melanoma cancer of the skin)
  • Coronary artery disease (CAD) or CAD equivalent including diabetes mellitus or National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) calculated 10-year coronary heart disease (CHD) risk of > 20%.
  • Known cirrhosis.
  • Known chronic active hepatitis B or C.
  • Thyroid-stimulating hormone (TSH) < 1.0 x lower limit of normal or > 1.0 x ULN.
  • Known inflammatory conditions, such as, but not limited to, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, inflammatory bowel disease (IBD), chronic pancreatitis, autoimmune hepatitis, myositis, or myopathy.
  • Pregnant or breast-feeding.
  • Previous intolerance to any statin or any of its components.
  • Use of any lipid-lowering therapies including all statin drugs, Omega 3 fatty acids/fish oil, red yeast rice, and niacin products ≥ 1 g/day (e.g., niacin, nicotinic acid, vitamin B3) taken within 45 days prior to study entry. More information on this criterion can be found in the study protocol.
  • Immunosuppressant use, such as, but not limited to, systemic or potentially systemic glucocorticoids (including nasal or inhaled steroids), azathioprine, tacrolimus, mycophenolate, sirolimus, rapamycin, or cyclosporine within 45 days prior to study entry.
  • Use of any systemic antineoplastic or immunomodulatory treatment, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry. More information on this criterion can be found in the study protocol.
  • Concurrent use of prohibited medications. More information on this criterion can be found in the study protocol.
  • Heavy alcohol use as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (http://pubs.niaaa.nih.gov/publications/Practitioner/pocketguide/pocket_guide3.htm) and alcohol or drug use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Current use of anticoagulation therapy other than ≤ 325 mg of daily aspirin.
  • Known coagulopathy, deep venous thrombosis, pulmonary embolism within 6 months prior to study entry.
  • Known active or recent (not fully resolved within 4 weeks prior to study entry) bacterial, fungal, parasitic, or viral infections.
  • Known history of recurrent rectal and/or genital herpes simplex virus (HSV) or varicella zoster virus (VZV) infection within 12 weeks prior to study entry.
  • Serious illness or trauma requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry.
  • History of stroke.
  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: NCT01351025

  Show 29 Study Locations
Sponsors and Collaborators
AIDS Clinical Trials Group
Pfizer
Investigators
Study Chair: Judith A. Aberg, M.D. NYU/Bellevue/HIV/AIDS CTU
Study Chair: Daniel E Nixon, D.O., Ph.D. Virginia Commonwealth University Medical Center
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01351025     History of Changes
Other Study ID Numbers: ACTG A5275, 1U01AI068636
Study First Received: November 8, 2010
Last Updated: June 19, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Inflammation
Blood Coagulation Disorders
Hemostatic Disorders
Pathologic Processes
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014