HIV InfectionsPhase 4NCT00355251
Influence of Atorvastatin on Viral Replication During Antiretroviral Treatment Interruption
A Phase 4 study testing Atorvastatin 40 mg/Atorvastatin 80 mg in people with HIV Infections, run by Germans Trias i Pujol Hospital at 1 site in Spain.
Trial summary
To determine the influence of atorvastatin on plasma viral replication when the latter is given before and during highly active anti-retroviral therapy (HAART) in patients with HIV infection and viral suppression. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Atorvastatin 40 mg/Atorvastatin 80 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteSpain
- Study dates
- Jul 2006to Feb 2007
- Phase
- Phase 4
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years.
- Patients with chronic infection by HIV-1 in stable highly active antiretroviral treatment (>= 6 months).
- Undetectable plasma viral load (<50 copies/mL) in the last 3 determinations over the last 6 months.
- CD4 > 500 cells/mm>=3 in the last two determinations.
- Documented prior viral load at some time of >15,000 copies/mL.
- Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.
- Signature of the informed consent
Who cannot join
- CD4 nadir <= 200 cells/mm3.
- Background of infections or other AIDS-defining pathology.
- Intercurrent infections in the last 6 months.
- Creatine kinase (CK) >= 500 U/L.
- AST or ALT >= 3 times higher than the upper limit of normality.
- Treatment with others statins, fibrates, macrolides or fluconazole in the last 3 months.
- Pregnancy or breastfeeding
- Patients participating in another clinical trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of the Influence of Atorvastatin in Plasma Viral Replication Given Prior to Antiretroviral Treatment Interruption in Patients With HIV-1 Infection and Viral Suppression.
To determine the influence of atorvastatin on plasma viral replication when the latter is given before and during highly active anti-retroviral therapy (HAART) in patients with HIV infection and viral suppression.
Read the detailed description
Recently, the inhibitory effect of the statins on the replication of the human immunodeficiency virus Type 1 (HIV-1) through two independent mechanisms of action has been described: the blockade of Rho guanosine triphosphatase that intervenes in the entry and exit of the virus and the blockade of the interaction between LFA-1 (leukocyte function antigen 1) and its ICAM 1 ligand (intercellular adhesion molecule 1) that intervenes in the process through which the virus binds to the target cell.
These initial data have led to the study of the effect of atorvastatin on the plasma replication of HIV in HIV+ patients that interrupt antiretroviral therapy (Ator Study 3) developed in our unit. The data of this study indicate that baseline plasma cholesterol determines viral load rebound on interrupting antiretroviral treatment. However, the introduction of atorvastatin on the day of interruption provided no virological or immunological benefit in comparison with an interruption of antiretrovirals without statins. This may be due to the fact that the potent inhibitory effect of atorvastatin is unable to compensate their activating effect on the production of HIV also described in our study.
Overall, our results pose a possible usefulness of atorvastatin in the control of viral replication if given before the interruption of antiretroviral therapy due to:
- Their capacity to reduce serum cholesterol at the time of interruption and consequently the cholesterol of the cell membrane.
- Their potent capacity to purge the HIV reservoir
Therefore, in this study we aim to investigate the impact of atorvastatin on viral replication when it is given 8 weeks before the interruption of the antiretroviral treatment and determine whether this impact is due to the reduction in serum and/or membrane cholesterol, or whether, on the other hand, there is a contribution by atorvastatin's capacity to induce the expression of viral products.
- Conditions
- HIV Infections
- Being tested
- Atorvastatin 40 mg/Atorvastatin 80 mg
- Keywords
- Atorvastatin, Viral replication, HIV-1, plasma cholesterol, Cell membrane cholesterol
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin 40 mg/Atorvastatin 80 mgDrug
Atorvastatin 40 mg/80 mg
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | 4 semanas manteniendo el tratamiento antirretroviral e iniciar atorvastatina 40 mg/día. A la semana 4 interrupción HAART y aumentar a 80 mg/día de atorvastatina hasta la semana 32 de seguimiento Receives: Drug: Atorvastatin 40 mg/Atorvastatin 80 mg |
| B | No intervention | 4 semanas manteniendo el tratamiento antirretroviral. A la semana 4 interrupción HAART hasta la semana 32 de seguimiento |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is viral load (HIV RNA) in plasma.
Measured: at 12 and 24 weeks
Secondary outcomes (6)
CD4 and CD8, absolute value, percentage and activation.
Measured: during the 32 weeks of follow-up
Total cholesterol, HDL and LDL in serum.
Measured: during the 32 weeks of follow-up
Cholesterol in cell membrane.
Measured: during the 32 weeks of follow-up
Symptoms reported by the patient following the interruption of the HAART therapy or signs detected by the clinician (classification according to the WHO), mainly those which may indicate acute antiretroviral symptoms.
Measured: during the 32 weeks of follow-up
Creatinine, urea, creatine kinase (CK), hepatic tests, (AST, ALT, GGT)
Measured: during the 32 weeks of follow-up
Proviral load.
Measured: during the 32 weeks of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2006 (estimated)
- Study startJul 2006
- Primary completionDec 2006
- Study completionFeb 2007
Why it stopped: On the basis of published results of SMART study, it has been observed that the results are worse in patients who have interrupted their treatments.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Germans Trias i Pujol Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Investigators
- Bonaventura Clotet, MD,PhD, Principal investigator, LLuita contra la Sida Foundation-HIV Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00355251
- Sponsor's protocol ID
- PRE-ATOR
- Other IDs
- 2005-005356-41, 2005
- Status last verified
- Feb 2014
- First submitted
- 19 Jul 2006
- Last updated
- 20 Mar 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Influence of Atorvastatin in Plasma Viral Replication Given Prior to Antiretroviral Treatment Interruption in Patients With HIV-1 Infection and Viral Suppression.
- ClinicalTrials.gov ID
- NCT00355251
- Acronym / sponsor ID
- PRE-ATOR
- Conditions
- HIV Infections
- Keywords
- Atorvastatin, Viral replication, HIV-1, plasma cholesterol, Cell membrane cholesterol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: On the basis of published results of SMART study, it has been observed that the results are worse in patients who have interrupted their treatments.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Germans Trias i Pujol HospitalUniversity, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Study start
- Jul 2006
- Primary completion
- Dec 2006 (actual)
- Study completion
- Feb 2007 (actual)
- First posted
- 21 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the influence of atorvastatin on plasma viral replication when the latter is given before and during highly active anti-retroviral therapy (HAART) in patients with HIV infection and viral suppression.
Detailed description
Recently, the inhibitory effect of the statins on the replication of the human immunodeficiency virus Type 1 (HIV-1) through two independent mechanisms of action has been described: the blockade of Rho guanosine triphosphatase that intervenes in the entry and exit of the virus and the blockade of the interaction between LFA-1 (leukocyte function antigen 1) and its ICAM 1 ligand (intercellular adhesion molecule 1) that intervenes in the process through which the virus binds to the target cell.
These initial data have led to the study of the effect of atorvastatin on the plasma replication of HIV in HIV+ patients that interrupt antiretroviral therapy (Ator Study 3) developed in our unit. The data of this study indicate that baseline plasma cholesterol determines viral load rebound on interrupting antiretroviral treatment. However, the introduction of atorvastatin on the day of interruption provided no virological or immunological benefit in comparison with an interruption of antiretrovirals without statins. This may be due to the fact that the potent inhibitory effect of atorvastatin is unable to compensate their activating effect on the production of HIV also described in our study.
Overall, our results pose a possible usefulness of atorvastatin in the control of viral replication if given before the interruption of antiretroviral therapy due to:
- Their capacity to reduce serum cholesterol at the time of interruption and consequently the cholesterol of the cell membrane.
- Their potent capacity to purge the HIV reservoir
Therefore, in this study we aim to investigate the impact of atorvastatin on viral replication when it is given 8 weeks before the interruption of the antiretroviral treatment and determine whether this impact is due to the reduction in serum and/or membrane cholesterol, or whether, on the other hand, there is a contribution by atorvastatin's capacity to induce the expression of viral products.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Atorvastatin 40 mg/Atorvastatin 80 mg4 semanas manteniendo el tratamiento antirretroviral e iniciar atorvastatina 40 mg/día. A la semana 4 interrupción HAART y aumentar a 80 mg/día de atorvastatina hasta la semana 32 de seguimiento |
| B | No intervention | –4 semanas manteniendo el tratamiento antirretroviral. A la semana 4 interrupción HAART hasta la semana 32 de seguimiento |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age >= 18 years.
- Patients with chronic infection by HIV-1 in stable highly active antiretroviral treatment (>= 6 months).
- Undetectable plasma viral load (<50 copies/mL) in the last 3 determinations over the last 6 months.
- CD4 > 500 cells/mm>=3 in the last two determinations.
- Documented prior viral load at some time of >15,000 copies/mL.
Key exclusion criteria (8 listed)
- CD4 nadir <= 200 cells/mm3.
- Background of infections or other AIDS-defining pathology.
- Intercurrent infections in the last 6 months.
- Creatine kinase (CK) >= 500 U/L.
- AST or ALT >= 3 times higher than the upper limit of normality.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atorvastatin 40 mg/Atorvastatin 80 mgAtorvastatin 40 mg/80 mg | Drug | A |
Primary outcome
The primary endpoint is viral load (HIV RNA) in plasma.
Time frame: at 12 and 24 weeks
6 secondary outcomes
CD4 and CD8, absolute value, percentage and activation.
Time frame: during the 32 weeks of follow-up
Total cholesterol, HDL and LDL in serum.
Time frame: during the 32 weeks of follow-up
Cholesterol in cell membrane.
Time frame: during the 32 weeks of follow-up
Symptoms reported by the patient following the interruption of the HAART therapy or signs detected by the clinician (classification according to the WHO), mainly those which may indicate acute antiretroviral symptoms.
Time frame: during the 32 weeks of follow-up
Creatinine, urea, creatine kinase (CK), hepatic tests, (AST, ALT, GGT)
Time frame: during the 32 weeks of follow-up
Proviral load.
Time frame: during the 32 weeks of follow-up
Results and safety
The study was stopped early (reason given: On the basis of published results of SMART study, it has been observed that the results are worse in patients who have interrupted their treatments.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bonaventura Clotet, MD,PhD principal investigator
LLuita contra la Sida Foundation-HIV Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atorvastatin 40 mg/Atorvastatin 80 mg in people with HIV Infections, run by Germans Trias i Pujol Hospital at 1 site in Spain.
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 7 inclusion and 8 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: stopped early, as of the sponsor's last update on 20 Mar 2014. 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 Spain. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was stopped early (reason given: On the basis of published results of SMART study, it has been observed that the results are worse in patients who have interrupted their treatments.). Results are not available in the source record.
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?
The primary endpoint is viral load (HIV RNA) in plasma. (time frame: at 12 and 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Mar 2014.