HIV InfectionsPhase 4NCT00773708
Pilot Opened Trial in HIV-infected Patients Including an Investigational Marketed Product
A Phase 4 study testing raltegravir in people with HIV Infections, run by Germans Trias i Pujol Hospital at 1 site in Spain.
Trial summary
This study aims to provide new knowledge about the pathogenesis of HIV infection, specifically, the role that immune activation and apoptotic activity play in immune recovery, and in particular, in the paradoxical immunologic response of some patients on antiretroviral therapy despite achievement of sustained and… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- raltegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteSpain
- Study dates
- Mar 2009to May 2011
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patient having a diagnosis of HIV infection, on continuously HAART for at least 2 years, including:
- 2 NRTI/NtRTIs (except ddI+TDF), plus
- 1 PI/ritonavir (lopinavir/ritonavir, atazanavir/ritonavir, fosamprenavir/ritonavir, tipranavir/ritonavir, darunavir/ritonavir) or 1 NNRTI (nevirapine or efavirenz)
- Undetectable plasma HIV-1 RNA (VL < 50 copies/mL) during the last 2 years prior to screening (with at least 4 determinations of viral load during this time period).
- Good treatment adherence.
- No presence of other factors which could contribute to CD4+ declines, such as treatment with chemotherapy, treatment with interferon/ribavirin, a ddI+TDF-containing regimen, etc, at least 12 months prior to screening.
- Patient classified as "discordant" who showed high level of CD8+HLADR+CD38+ and cell death values at the screening (see reference values in the definition section in page 9: 4.2. AIMS).
- Voluntary written informed consent.
Who cannot join
- Pregnancy or fertile women willing to be pregnant.
- Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion.
- Hepatic toxicity (AST, ALT levels grade +/= 3).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study to Assess the Role of Immune Activation and Apoptosis as a Marker for Treatment Intensification With Raltegravir in Hiv-infected Patients on Antiretroviral Therapy With Long-term Viral Suppression and Unfavourable Immunologic Response (Discordant Patients: v+i-)
This study aims to provide new knowledge about the pathogenesis of HIV infection, specifically, the role that immune activation and apoptotic activity play in immune recovery, and in particular, in the paradoxical immunologic response of some patients on antiretroviral therapy despite achievement of sustained and complete viral suppression. In this regard, the investigators will prospectively evaluate the impact of intensification with Raltegravir in those "discordants" patients with high index of immune activation, measured as the percentage of CD8+HLADR+CD38+ cells. This will provide relevant information on the effectiveness of this drug in guided intensification regimens.
Read the detailed description
One of the many adverse consequences of the human immunodeficiency virus (HIV) infection is the increase in the rate of lymphocyte cell death (Badley AD, Blood. 2000; 96:2951-64). Increased lymphocyte death is associated with the level of activation of the immune system (Gougeon ML. Nat Rev Immunol. 2003: 3:392-404), along with the disregulation of the cytokine network and a plethora of cytotoxic effects induced by HIV proteins (Badley AD, Blood. 2000; 96:2951-64). Hence, cell death can be observed in vivo not only in CD4+ cells, which are the main target of HIV, but also in CD8 T cells. Current knowledge suggest that immune activation and different mechanisms of cell death play a determinant role in T-lymphocyte (CD4+) loss during HIV infection and recovery after HAART (Bofill M et al AIDS. 1996 :827-34).
Highly active antiretroviral treatment (HAART) induces a decline in the level of immune activation and lymphocyte apoptosis in HIV-infected patients as a result of a reduction in viral replication (Kolber MA, et al, Clin Immunol. 2007 [Epub ahead of print]). This reduction contributes to the recovery of immune system associated with antiretroviral therapy. In addition to this effect, which is induced through the reduction in viral load, antiretroviral therapy has been implicated in the regulation of apoptosis in different cell types, inhibiting or activating the process and influencing treatment efficacy and toxicity (Petit F, et al.Trends Pharmacol Sci. 2005. 26:258-64).
Interestingly, it is not always true that antiretroviral therapy and viral suppression are associated with progressive immune recovery. Approximately 30% of patients present a paradoxical response to treatment, achieving progressive increases in immunity (measured by CD4+ count) despite failing to achieve viral suppression, or, vice versa, patients who maintain or reduce CD4+ cell count despite achieving viral suppression. Indeed, it is well known that higher CD8 activation is associated with fewer treatment-mediated CD4 gain. Each 10% increase in activated CD8+HLADR+CD38+ mean 90 fewer CD4 cell gained (Hunt PW et al J Infect Dis. 2003. 187:1534-43). The failure of recover CD4 T cells may rely on a incomplete viral suppression than could be responsible for increased immune activation and lymphocyte death. Recently, it has been pointed out that intensification strategies may be useful in reducing activation and improving CD4 T cell recovery (Kolber MA, et al, Clin Immunol. 2007 [Epub ahead of print]).
- Conditions
- HIV Infections
- Being tested
- raltegravir
- Keywords
- HIV infection, Discordant patient, CD4 recovery, intensification antiretroviral therapy, raltegravir, HIV-1 infected patient classified as "discordant" who showed high level of CD8+HLADR+CD38+ and cell death values at the screening
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
raltegravirDrug
Also called N/P.
intensify their therapy with Raltegravir(RAL):1 Protease inhibitor plus 2 nucleoside reverse transcriptase inhibitor plus RAL or 1 non-nucleoside reverse transcriptase inhibitor plus 2 nucleoside reverse transcriptase inhibitor plus RAL
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | intensify their triple-drug therapy with Raltegravir (RAL) Receives: Drug: raltegravir |
| 2 | No intervention | Continue with the same antiretroviral therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4 cell count
Measured: From Basal to 48 week (last visit) every 3 months
Secondary outcomes (5)
Epidemiologic variables: Age, sex, time of HIV diagnosis/duration of HIV infection, duration of antiretroviral treatment with HAART, duration of treatment with a PI, HIV infection status/CDC disease stage. Epidemiologic, virologic, and immunologic data
Measured: Baseline
Virologic and immunologic variables: Time/duration of viral suppression, nadir CD4+ count, change in CD4+ count (absolute and percentage) since initiation of antiretroviral therapy, since initiation of HAART, and since achieving and undetectable viral
Measured: From Basal to 48 week (last visit) every 3 months
Apoptotic variables: Cell death in CD4 and CD8 cells, defined as the percentage of cells which present a weak DIOC measurement (DIOC low) after 1 or 4 days of culture.
Measured: From Basal to 48 week (last visit) every 3 months
The toxicity parameters will be evaluated: Hematology: Hematocrit, red blood cell count, hemoglobin, MCV, lymphocyte, platelet count, quick Index. • Biochemistry: glucose, total cholesterol, HDL and LDL cholesterol, triglycerides, urea, creatinine, A
Measured: From Basal to 48 week (last visit) every 3 months
Clinical adverse effects and clinical events
Measured: From Basal to 48 week (last visit) every 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2008 (estimated)
- Study startMar 2009
- Primary completionMay 2011
- Study completionMay 2011
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
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Germans Trias i Pujol Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sílvia Gel, Germans Trias i Pujol Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00773708
- Sponsor's protocol ID
- DISCOR-RAL
- Status last verified
- Sep 2011
- First submitted
- 14 Oct 2008
- Last updated
- 11 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Assess the Role of Immune Activation and Apoptosis as a Marker for Treatment Intensification With Raltegravir in Hiv-infected Patients on Antiretroviral Therapy With Long-term Viral Suppression and Unfavourable Immunologic Response (Discordant Patients: v+i-)
- ClinicalTrials.gov ID
- NCT00773708
- Acronym / sponsor ID
- DISCOR-RAL
- Conditions
- HIV Infections
- Keywords
- HIV infection, Discordant patient, CD4 recovery, intensification antiretroviral therapy, raltegravir, HIV-1 infected patient classified as "discordant" who showed high level of CD8+HLADR+CD38+ and cell death values at the screening
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Germans Trias i Pujol HospitalUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 16 Oct 2008 (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.
This study aims to provide new knowledge about the pathogenesis of HIV infection, specifically, the role that immune activation and apoptotic activity play in immune recovery, and in particular, in the paradoxical immunologic response of some patients on antiretroviral therapy despite achievement of sustained and complete viral suppression. In this regard, the investigators will prospectively evaluate the impact of intensification with Raltegravir in those "discordants" patients with high index of immune activation, measured as the percentage of CD8+HLADR+CD38+ cells. This will provide relevant information on the effectiveness of this drug in guided intensification regimens.
Detailed description
One of the many adverse consequences of the human immunodeficiency virus (HIV) infection is the increase in the rate of lymphocyte cell death (Badley AD, Blood. 2000; 96:2951-64). Increased lymphocyte death is associated with the level of activation of the immune system (Gougeon ML. Nat Rev Immunol. 2003: 3:392-404), along with the disregulation of the cytokine network and a plethora of cytotoxic effects induced by HIV proteins (Badley AD, Blood. 2000; 96:2951-64). Hence, cell death can be observed in vivo not only in CD4+ cells, which are the main target of HIV, but also in CD8 T cells. Current knowledge suggest that immune activation and different mechanisms of cell death play a determinant role in T-lymphocyte (CD4+) loss during HIV infection and recovery after HAART (Bofill M et al AIDS. 1996 :827-34).
Highly active antiretroviral treatment (HAART) induces a decline in the level of immune activation and lymphocyte apoptosis in HIV-infected patients as a result of a reduction in viral replication (Kolber MA, et al, Clin Immunol. 2007 [Epub ahead of print]). This reduction contributes to the recovery of immune system associated with antiretroviral therapy. In addition to this effect, which is induced through the reduction in viral load, antiretroviral therapy has been implicated in the regulation of apoptosis in different cell types, inhibiting or activating the process and influencing treatment efficacy and toxicity (Petit F, et al.Trends Pharmacol Sci. 2005. 26:258-64).
Interestingly, it is not always true that antiretroviral therapy and viral suppression are associated with progressive immune recovery. Approximately 30% of patients present a paradoxical response to treatment, achieving progressive increases in immunity (measured by CD4+ count) despite failing to achieve viral suppression, or, vice versa, patients who maintain or reduce CD4+ cell count despite achieving viral suppression. Indeed, it is well known that higher CD8 activation is associated with fewer treatment-mediated CD4 gain. Each 10% increase in activated CD8+HLADR+CD38+ mean 90 fewer CD4 cell gained (Hunt PW et al J Infect Dis. 2003. 187:1534-43). The failure of recover CD4 T cells may rely on a incomplete viral suppression than could be responsible for increased immune activation and lymphocyte death. Recently, it has been pointed out that intensification strategies may be useful in reducing activation and improving CD4 T cell recovery (Kolber MA, et al, Clin Immunol. 2007 [Epub ahead of print]).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: raltegravirintensify their triple-drug therapy with Raltegravir (RAL) |
| 2 | No intervention | –Continue with the same antiretroviral therapy |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Patient having a diagnosis of HIV infection, on continuously HAART for at least 2 years, including:
- Undetectable plasma HIV-1 RNA (VL < 50 copies/mL) during the last 2 years prior to screening (with at least 4 determinations of viral load during this time period).
- Good treatment adherence.
- No presence of other factors which could contribute to CD4+ declines, such as treatment with chemotherapy, treatment with interferon/ribavirin, a ddI+TDF-containing regimen, etc, at least 12 months prior to screening.
- Patient classified as "discordant" who showed high level of CD8+HLADR+CD38+ and cell death values at the screening (see reference values in the definition section in page 9: 4.2. AIMS).
Key exclusion criteria (3 listed)
- Pregnancy or fertile women willing to be pregnant.
- Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion.
- Hepatic toxicity (AST, ALT levels grade +/= 3).
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 |
|---|---|---|
| raltegravirAlso: N/P.intensify their therapy with Raltegravir(RAL):1 Protease inhibitor plus 2 nucleoside reverse transcriptase inhibitor plus RAL or 1 non-nucleoside reverse transcriptase inhibitor plus 2 nucleoside reverse transcriptase inhibitor plus RAL | Drug | 1 |
Primary outcome
CD4 cell count
Time frame: From Basal to 48 week (last visit) every 3 months
5 secondary outcomes
Epidemiologic variables: Age, sex, time of HIV diagnosis/duration of HIV infection, duration of antiretroviral treatment with HAART, duration of treatment with a PI, HIV infection status/CDC disease stage. Epidemiologic, virologic, and immunologic data
Time frame: Baseline
Virologic and immunologic variables: Time/duration of viral suppression, nadir CD4+ count, change in CD4+ count (absolute and percentage) since initiation of antiretroviral therapy, since initiation of HAART, and since achieving and undetectable viral
Time frame: From Basal to 48 week (last visit) every 3 months
Apoptotic variables: Cell death in CD4 and CD8 cells, defined as the percentage of cells which present a weak DIOC measurement (DIOC low) after 1 or 4 days of culture.
Time frame: From Basal to 48 week (last visit) every 3 months
The toxicity parameters will be evaluated: Hematology: Hematocrit, red blood cell count, hemoglobin, MCV, lymphocyte, platelet count, quick Index. • Biochemistry: glucose, total cholesterol, HDL and LDL cholesterol, triglycerides, urea, creatinine, A
Time frame: From Basal to 48 week (last visit) every 3 months
Clinical adverse effects and clinical events
Time frame: From Basal to 48 week (last visit) every 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 raltegravir 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 8 inclusion and 3 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 11 Mar 2015. 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 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?
CD4 cell count (time frame: From Basal to 48 week (last visit) every 3 months). 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 11 Mar 2015.