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HIV-1 InfectionPhase 2NCT01351025

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

A Phase 2 study testing atorvastatin in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 31 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1 Infection
What is being tested?
atorvastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
98 participants
Where
31 sitesin 2 countries
Study dates
14 Apr 2011to May 2014
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
  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

31 sites in 2 countries.

31 sites in 2 countries

United States30 sites

  • University of Colorado Hospital CRS (6101)

    Aurora, Colorado, 80045

  • 31788 Alabama CRS

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital ACTG CRS (101)

    Boston, Massachusetts, 02114

  • Brigham and Women's Hosp. ACTG CRS (107)

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Med. Ctr., ACTG CRS (103)

    Boston, Massachusetts, 02215

  • Cooper Univ. Hosp. CRS (31476)

    Camden, New Jersey, 08103

  • Unc Aids Crs (3201)

    Chapel Hill, North Carolina, 27516

  • Northwestern University CRS (2701)

    Chicago, Illinois, 60611

  • Univ. of Cincinnati CRS (2401)

    Cincinnati, Ohio, 45267

  • Case CRS (2501)

    Cleveland, Ohio, 44106

  • Metro Health CRS (2503)

    Cleveland, Ohio, 44109

  • The Ohio State Univ. AIDS CRS (2301)

    Columbus, Ohio, 43210

  • Wayne State Univ. CRS (31478)

    Detroit, Michigan, 48201

  • Henry Ford Hosp. CRS (31472)

    Detroit, Michigan, 48202

  • Duke Univ. Med. Ctr. Adult CRS (1601)

    Durham, North Carolina, 27710

  • Houston AIDS Research Team CRS (31473)

    Houston, Texas, 77030

  • UCLA CARE Center CRS (601)

    Los Angeles, California, 90095

  • Cornell CRS (7804)

    New York, New York, 10011

  • NY Univ. HIV/AIDS CRS (401)

    New York, New York, 10016

  • New Jersey Medical School-Adult Clinical Research Ctr. CRS (31486)

    Newark, New Jersey, 07103

  • Hosp. of the Univ. of Pennsylvania CRS (6201)

    Philadelphia, Pennsylvania, 19104

  • Pitt CRS (1001)

    Pittsburgh, Pennsylvania, 15213

  • Virginia Commonwealth Univ. Medical Ctr. CRS (31475)

    Richmond, Virginia, 23219

  • AIDS Care CRS (1101)

    Rochester, New York, 14642

  • University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

    Rochester, New York, 14642

  • Ucsd, Avrc Crs (701)

    San Diego, California, 92103

  • University of Washington AIDS CRS (1401)

    Seattle, Washington, 98104

  • Washington U CRS (2101)

    St Louis, Missouri, 63110

  • Harbor-UCLA Med. Ctr. CRS (603)

    Torrance, California, 90502

  • Georgetown University CRS (GU CRS) (1008)

    Washington D.C., District of Columbia, 20007

Other trials in United States

Puerto Rico1 site

  • Puerto Rico-AIDS CRS (5401)

    San Juan, 00935

Other trials in Puerto Rico

About this study

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

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.

Read the 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.

Conditions
HIV-1 Infection
Being tested
atorvastatin, placebo for atorvastin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • atorvastatinDrug

    Also called Lipitor

    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

  • atorvastatinDrug

    Also called Lipitor

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

  • placebo for atorvastinDrug

    Also called placebo

    One tablet once daily for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, then increase the dose to two tablets once daily.

Study groups in NCT01351025
Study groupRoleWhat they receive
Arm A: atorvastatin / placeboExperimentalAt study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated atorvastatin at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at the week 4 visit. At week 20, atorvastatin was stopped for a 4-week washout period. At week 24, placebo was started for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the placebo dose was doubled at week 28. At week 44, the placebo was stopped to allow for another 4-week washout period.
Receives: Drug: atorvastatin; Drug: placebo for atorvastin
Arm B: placebo / atorvastatinExperimentalAt study entry (week 0), participants continued the entry boosted PI-based antiretroviral regimen (not provided by the study) and initiated placebo for 4 weeks. If no symptoms or lab findings suggestive of toxicity were found, the dose of placebo was doubled at the week 4 visit. At week 20, the placebo was stopped for a 4-week washout period. At week 24, atorvastatin was started at a daily dose of 10 mg for 4 weeks. If no symptoms or lab findings suggestive of atorvastatin toxicity were found, the dose of atorvastatin was increased to 20 mg daily at week 28. At week 44, atorvastatin was stopped to allow for another 4-week washout period.
Receives: Drug: atorvastatin; Drug: placebo for atorvastin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    IL-6 (Interleukin 6) in log10 pg/mL: Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])

    Measured: baseline, week 20, week 24, and week 44

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

    CD4+ T-cell activation percent (% CD38+/DR+ of CD4+): Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])

    Measured: baseline, week 20, week 24, and week 44

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

    D-dimer in log10 ng/mL: Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])

    Measured: baseline, week 20, week 24, and week 44

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

    CD8+ T-cell activation percent (% CD38+/DR+ of CD8+): Difference between [change from week 24 to week 44] and [change from baseline to week 20] (i.e. [week 44 - week 24] - [week 20 - baseline])

    Measured: baseline, week 20, week 24, and week 44

Secondary outcomes (8)

  1. Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in MCP-1 (log10 Transformed)

    Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages.

    Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

    Measured: baseline, week 20, week 24, and week 44

  2. Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in IP-10 (log10 Transformed)

    IFN-gamma-inducible protein 10 (IP-10 or CXCL10) is a chemokine secreted from cells stimulated with type I and II IFNs and LPS, is also a chemoattractant for activated T cells.

    Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

    Measured: baseline, week 20, week 24, and week 44

  3. Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in CD40L (log10 Transformed)

    Cluster of differentiation 40 (CD40L) is a costimulatory protein found on antigen presenting cells and is required for their activation.

    Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

    Measured: baseline, week 20, week 24, and week 44

  4. Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in sCD14 (log10 Transformed)

    Soluble cluster of differentiation 14 (sCD14) is a human gene. Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

    Measured: baseline, week 20, week 24, and week 44

  5. Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in P-selectin (log10 Transformed)

    P-selectin is a protein that in humans encoded by the SELP gene. P-selectin functions as a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and activated platelets.

    Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

    Measured: baseline, week 20, week 24, and week 44

  6. Difference Between [Change From Week 24 to Week 44] and Change From [Baseline to Week 20] in sCD163 (log10 Transformed)

    CD163 (Cluster of Differentiation 163) is a protein that in humans encoded by the CD163 gene; and sCD163 is soluble CD163.

    Difference between [change from week 24 to week 44] and change from [baseline to week 20] is defined as [week 44 - week 24] - [week 20 - baseline].

    Measured: baseline, week 20, week 24, and week 44

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

    Safety endpoints are defined as grade ≥ 2 signs and symptoms, laboratory abnormalities, AST/ALT > 3 X ULN, and adverse events prior to study treatment cross-over (baseline to week 24).

    The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

    Measured: week 0 to week 24

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

    Safety endpoints are defined as grade ≥ 2 signs and symptoms, laboratory abnormalities, AST/ALT > 3 X ULN, and adverse events after study treatment cross-over (week 24 to week 48).

    The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

    Measured: week 24 to week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2011 (estimated)
  2. Study start14 Apr 2011
  3. Primary completionMay 2014
  4. Study completionMay 2014

Resources

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
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01351025
Sponsor's protocol ID
ACTG A5275
Other IDs
1U01AI068636
Status last verified
Jul 2021
First submitted
8 Nov 2010
Last updated
3 Aug 2021
Data monitoring committee
Yes

Publications

  • Rahman F, Brates I, Aweeka F, Bosch RJ, Deitchman A, Nixon D, Aberg JA. Evaluating the effect of atorvastatin exposure and vitamin D levels on lipid outcomes in people with HIV-1 with suppressed HIV-1 RNA and LDL cholesterol <130 mg/dL. HIV Med. 2023 Jun;24(6):749-753. doi: 10.1111/hiv.13453. Epub 2022 Dec 22.

    PubMed 36549898

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing atorvastatin in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 31 sites in 2 countries.

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 14 inclusion and 19 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 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Puerto Rico. 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 4 Aug 2015). 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?

Difference Between [Change From Week 24 to Week 44] and [Change From Baseline to Week 20] in log10 IL-6 (time frame: baseline, week 20, week 24, and week 44). The study lists 4 primary outcomes in all. 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 NCT01351025, which also lists 1 linked publication.

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 3 Aug 2021.

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