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

Information source: AIDS Clinical Trials Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV-1 Infection

Intervention: atorvastatin (Drug); atorvastatin (Drug); placebo for atorvastin (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: AIDS Clinical Trials Group

Official(s) and/or principal investigator(s):
Judith A. Aberg, M.D., Study Chair, Affiliation: NYU/Bellevue/HIV/AIDS CTU
Daniel E Nixon, D.O., Ph.D., Study Chair, Affiliation: Virginia Commonwealth University Medical Center

Summary

ACTG A5275 was a prospective, double-blind, randomized, placebo-controlled cross-over design 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 on stable protease inhibitor based antiretroviral therapy with fasting LDL cholesterol < 130 mg/dL. 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 evaluated if atorvastatin is safe for people with HIV who are also taking medication for HIV.

Clinical Details

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 < 130 mg/dL

Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 IL-6

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in CD4+ T-cell Activation Percent

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 D-dimer

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in CD8+ T-cell Activation Percent

Secondary outcome:

Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in Biomarkers

Number of Participants With Safety Endpoints Before Study Treatment Cross-over (Baseline to Week 24)

Number of Participants With Safety Endpoints After Study Treatment Cross-over (Week 24 to Week 48)

Detailed description: 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. 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 have been 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 have been 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 was permissible if RNA levels immediately before and after were 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 was 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 was the original D-dimer criterion. It was revised to ≥ 0. 25 ug/mL four months after the first enrollment, and subsequently the D-dimer eligibility criterion was completely cut off a year later.

- For females of reproductive potential (women who had not been post-menopausal for at

least 24 consecutive months, i. e., who had menses within 24 months prior to study entry), or women who had not undergone surgical sterilization, specifically hysterectomy or bilateral oophorectomy or tubal ligation) required 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 had to confirm that these samples had 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.

Locations and Contacts

Puerto Rico-AIDS CRS (5401), San Juan 00935, Puerto Rico

31788 Alabama CRS, Birmingham, Alabama 35294, United States

UCLA CARE Center CRS (601), Los Angeles, California 90095, United States

Ucsd, Avrc Crs (701), San Diego, California 92103, United States

Harbor-UCLA Med. Ctr. CRS (603), Torrance, California 90502, United States

University of Colorado Hospital CRS (6101), Aurora, Colorado 80045, United States

Georgetown University CRS (GU CRS) (1008), Washington, District of Columbia 20007, United States

Northwestern University CRS (2701), Chicago, Illinois 60611, United States

Beth Israel Deaconess Med. Ctr., ACTG CRS (103), Boston, Massachusetts 02215, United States

Brigham and Women's Hosp. ACTG CRS (107), Boston, Massachusetts 02115, United States

Massachusetts General Hospital ACTG CRS (101), Boston, Massachusetts 02114, United States

Henry Ford Hosp. CRS (31472), Detroit, Michigan 48202, United States

Wayne State Univ. CRS (31478), Detroit, Michigan 48201, United States

Washington U CRS (2101), St. Louis, Missouri 63110, United States

Cooper Univ. Hosp. CRS (31476), Camden, New Jersey 08103, United States

New Jersey Medical School-Adult Clinical Research Ctr. CRS (31486), Newark, New Jersey 07103, United States

Cornell CRS (7804), New York, New York 10011, United States

NY Univ. HIV/AIDS CRS (401), New York, New York 10016, United States

AIDS Care CRS (1101), Rochester, New York 14642, United States

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787), Rochester, New York 14642, United States

Unc Aids Crs (3201), Chapel Hill, North Carolina 27516, United States

Duke Univ. Med. Ctr. Adult CRS (1601), Durham, North Carolina 27710, United States

Univ. of Cincinnati CRS (2401), Cincinnati, Ohio 45267, United States

Case CRS (2501), Cleveland, Ohio 44106, United States

Metro Health CRS (2503), Cleveland, Ohio 44109, United States

The Ohio State Univ. AIDS CRS (2301), Columbus, Ohio 43210, United States

Hosp. of the Univ. of Pennsylvania CRS (6201), Philadelphia, Pennsylvania 19104, United States

Pitt CRS (1001), Pittsburgh, Pennsylvania 15213, United States

Houston AIDS Research Team CRS (31473), Houston, Texas 77030, United States

Virginia Commonwealth Univ. Medical Ctr. CRS (31475), Richmond, Virginia 23219, United States

University of Washington AIDS CRS (1401), Seattle, Washington 98104, United States

Additional Information

Starting date: April 2011
Last updated: July 7, 2015

Page last updated: August 23, 2015

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