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HIV SeropositivityPhase 2LIVENCT00721305

Lovastatin: Immunomodulatory Value Evaluation

A Phase 2 study testing Lovastatin in people with HIV Seropositivity, run by Universidad de Antioquia at 1 site in Colombia.

Completed

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

Official record
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Trial summary

The purpose of this study is to determine whether the long-term administration of statins may benefit the clinical and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV Seropositivity
What is being tested?
Lovastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
112 participants
Where
1 siteColombia
Study dates
Aug 2008to Jul 2011
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Asymptomatic HIV-1 seropositive individuals, with age ≥ 18 years, who are HAART naive
  • HIV-1 infection confirmed by:
  • positive Western-blot test dated at least six months before admission to the study;
  • a Western-blot test within the last six months, which was also positive for the p31 and p66 bands
  • Detectable viral load < 100,000 copies/ml
  • CD4+ T cell count ≥ 350 cells/ul

Who cannot join

  • Inability or unwillingness of patients to give written informed consent.
  • Main residence outside Medellin and its metropolitan area, or any indication of difficulties in the follow-up period
  • Participation in other clinical trials
  • Evidence that the patient will exhibit low adherence to intervention and follow-up (Morisky-Green test)
  • Pregnancy or breastfeeding
  • Any type of antiretroviral treatment before admission to the study, and therapy with lipid-lowering drugs during the last six months
Show all 16Show fewer
  • Antecedents of allergy, contraindications or intolerance to statins
  • Patients receiving medications which can generate relevant interactions with lovastatin: clarithromycin, erythromycin, azithromycin, itraconazole, ketoconazole, nefodozone, cimetidine, rifampin, phenobarbital, carbamazepine, phenytoin.
  • Unwillingness to avoid the consumption of Citrus paradise (grapefruit juice) or Saint John's Wort (Hypericum)
  • Opportunistic infections or any type of AIDS-defining disease
  • Chronic active hepatitis (B or C)
  • Any hepatocellular disease, indicated by elevation of liver enzymes (AST or ALT) more than twice the reference value
  • Renal failure, indicated by serum creatinine ≥ 2 mg/dl
  • Myopathy, indicated by an elevation of creatine phosphokinase (CPK) more than five times the reference values
  • Infection or acute disease that requires in-patient treatment
  • Active substance-related disorders

Trial locations and contacts

1 site in 1 country.

Colombia1 site

  • Group of Immunovirology, Research Universitary Center, University of Antioquia

    Medellín, Antioquia

Other trials in Colombia

About this study

Official title: Antiretroviral Effect of Lovastatin on HIV-1-infected Individuals Without Highly Active Antiretroviral Therapy (HAART): A Phase-II Randomized Clinical Trial (RCT)

The purpose of this study is to determine whether the long-term administration of statins may benefit the clinical and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required.

Read the detailed description

Despite the fact that HAART produces a decrease in HIV-1 replication and plasma HIV-1 RNA levels, and allows an increase in the CD4 T-cell count that leads to a diminution in the incidence of opportunistic infections and mortality, the cost and complexity of HAART regimens, the growing list of long-term side effects, and the eventual development of resistance have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunological effects that are related and unrelated to their cholesterol-lowering activity. HIV-1 requires cholesterol and lipid rafts for several key stages of its replication cycle; statins-mediated depletion of cholesterol alters the capacity of a cell to form lipid rafts and decreases the HIV-1 infectivity. On the other hand, statins may exert significant modulator effects in the balance of the cytokine network, and alter the activity of Rho GTPases and LFA-1 and ICAM-1 adhesion molecules. Preliminary studies showed that statins (Lovastatin) had anti HIV-1 activity, and that its administration was safe and efficient to control HIV-1 infection in chronically infected individuals who did not receive HAART (in terms of decreasing viral load and increasing CD4 T-cell count). Because very limited clinical data are available on this topic, this study will be conducted.

Being tested
Lovastatin, placebo
Keywords
Type 1 human immunodeficiency virus infection, Lovastatin, Adaptive Immunity, Cellular cholesterol, Rho GTPases, Lymphocyte function-associated antigen-1
Medical subject headings
HIV Seropositivity

What participants receive

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

  • LovastatinDrug

    Also called statin

    Lovastatin 40 mg daily (2 tablets of 20 mg each, p.o.), during twelve months until the end of the study, or before the end of the study if any AIDS defining disease or toxicity appear

  • placeboOther

    Placebo will be administered daily (2 tablets which will look externally identical to intervention: wrapped in the same way, with the same size, shape and color), during twelve months until the end of the study, or before the end of the study if any AIDS defining disease or toxicity appear

Study groups in NCT00721305
Study groupRoleWhat they receive
1ExperimentalIn this arm, subjects will receive 40 mg of Lovastatin (2 tablets of 20 mg each, p.o.), in a daily doses, during twelve months
Receives: Drug: Lovastatin
2Placebo comparatorIn this arm, subjects will receive placebo (2 tablets which will look externally identical to lovastatin: wrapped in the same way, with the same size, shape and color)
Receives: Other: placebo

What is being measured

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

  1. 1. HIV-1 viral load measured as RNA copies per ml of peripheral blood 2. CD4 T-cell count measured as cells per ul of peripheral blood

    Measured: Before, 6 and twelve months after the intervention

Secondary outcomes (1)

  1. CD8+ T cell count, CD4/CD8 ratio, Expression of CD38 and HLA-DR, Total serum cholesterol, Cellular cholesterol, Activity of LFA-1 and ICAM-1, Activity of Rho GTPases, Monthly frequency of AIDS defining diseases, hospitalization and mortality

    Measured: Before, 6 and twelve months after the intervention

Timeline

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

  1. First posted24 Jul 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionJul 2011
  4. Study completionJul 2011

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
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00721305
Sponsor's protocol ID
COLCIENCIAS 111540820508
Acronym
LIVE
Status last verified
Sep 2011
First submitted
22 Jul 2008
Last updated
4 Oct 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • UNAIDS and WHO. AIDS epidemic update 2004. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO); 2004 December 2004

  • Instituto Nacional de Salud. Programa Nacional de Prevención y control ITS/SIDA. Colombia 1983-2002. Bogotá: Instituto Nacional de Salud, Ministerio de Salud de la República de Colombia; 2003

  • Cohen DE, Walker BD. Human immunodeficiency virus pathogenesis and prospects for immune control in patients with established infection. Clin Infect Dis. 2001 Jun 15;32(12):1756-68. doi: 10.1086/320759. Epub 2001 May 16.

    PubMed 11360218

  • Giorgi JV, Liu Z, Hultin LE, Cumberland WG, Hennessey K, Detels R. Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr (1988). 1993 Aug;6(8):904-12.

    PubMed 7686224

  • Hazenberg MD, Otto SA, van Benthem BH, Roos MT, Coutinho RA, Lange JM, Hamann D, Prins M, Miedema F. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS. 2003 Sep 5;17(13):1881-8. doi: 10.1097/00002030-200309050-00006.

    PubMed 12960820

  • Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.

    PubMed 9516219

  • Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997 Nov 14;278(5341):1295-300. doi: 10.1126/science.278.5341.1295.

    PubMed 9360927

  • Aberg JA, Zackin RA, Brobst SW, Evans SR, Alston BL, Henry WK, Glesby MJ, Torriani FJ, Yang Y, Owens SI, Fichtenbaum CJ; ACTG 5087 Study Team. A randomized trial of the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities: AIDS Clinical Trials Group Study 5087. AIDS Res Hum Retroviruses. 2005 Sep;21(9):757-67. doi: 10.1089/aid.2005.21.757.

    PubMed 16218799

  • Calza L, Manfredi R, Chiodo F. Statins and fibrates for the treatment of hyperlipidaemia in HIV-infected patients receiving HAART. AIDS. 2003 Apr 11;17(6):851-9. doi: 10.1097/00002030-200304110-00010.

    PubMed 12660532

  • Fehr T, Kahlert C, Fierz W, Joller-Jemelka HI, Riesen WF, Rickli H, Wuthrich RP, Ammann P. Statin-induced immunomodulatory effects on human T cells in vivo. Atherosclerosis. 2004 Jul;175(1):83-90. doi: 10.1016/j.atherosclerosis.2004.02.016.

    PubMed 15186950

  • Yilmaz A, Reiss C, Tantawi O, Weng A, Stumpf C, Raaz D, Ludwig J, Berger T, Steinkasserer A, Daniel WG, Garlichs CD. HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new implications for atherosclerosis. Atherosclerosis. 2004 Jan;172(1):85-93. doi: 10.1016/j.atherosclerosis.2003.10.002.

    PubMed 14709361

  • Kwak B, Mulhaupt F, Veillard N, Pelli G, Mach F. The HMG-CoA reductase inhibitor simvastatin inhibits IFN-gamma induced MHC class II expression in human vascular endothelial cells. Swiss Med Wkly. 2001 Jan 27;131(3-4):41-6. doi: 10.4414/smw.2001.06144.

    PubMed 11219190

  • Liao Z, Cimakasky LM, Hampton R, Nguyen DH, Hildreth JE. Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1. AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1009-19. doi: 10.1089/088922201300343690.

    PubMed 11485618

  • Del Real G, Jimenez-Baranda S, Lacalle RA, Mira E, Lucas P, Gomez-Mouton C, Carrera AC, Martinez-A C, Manes S. Blocking of HIV-1 infection by targeting CD4 to nonraft membrane domains. J Exp Med. 2002 Aug 5;196(3):293-301. doi: 10.1084/jem.20020308.

    PubMed 12163558

  • del Real G, Jimenez-Baranda S, Mira E, Lacalle RA, Lucas P, Gomez-Mouton C, Alegret M, Pena JM, Rodriguez-Zapata M, Alvarez-Mon M, Martinez-A C, Manes S. Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med. 2004 Aug 16;200(4):541-7. doi: 10.1084/jem.20040061.

    PubMed 15314078

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lovastatin in people with HIV Seropositivity, run by Universidad de Antioquia at 1 site in Colombia.

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 6 inclusion and 16 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 4 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Colombia. 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. Some participants in this study may receive a placebo. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

1. HIV-1 viral load measured as RNA copies per ml of peripheral blood 2. CD4 T-cell count measured as cells per ul of peripheral blood (time frame: Before, 6 and twelve months after the intervention). 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 NCT00721305, which also lists 74 linked publications.

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 4 Oct 2011.

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