HIVPhase 2OUSCOX2NCT01269515
Immunomodulating Therapy and Improved Vaccination Responses by Cox-2 Inhibitor in HIV-infected Patients
A Phase 2 study testing Etoricoxib in people with HIV, run by Dag Kvale at 2 sites in Norway.
Trial summary
Chronic immune activation is a central feature of HIV-infection, and the degree of activated T-cells is a better predictor of disease progression and mortality than plasma viral load. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV
- What is being tested?
- Etoricoxib
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesNorway
- Study dates
- Oct 2010to Nov 2014
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ART- group: Confirmed diagnosis of HIV infection < 8 years prestudy
- no HIV-related clinical manifestations including acute HIV infection
- no current indication or use for antiretroviral treatment
- CD4+ count > 350 x 10^6 /l
- HIV RNA > 2000 copies/ml
- ART+ group: Confirmed diagnosis of HIV infection
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- no HIV-related clinical manifestations including acute HIV infection
- On stabile effective antiretroviral treatment (HIV RNA <50 copies/ml)
- CD4+ count < 500 x 10^6 /l
- HIV RNA > 2000 copies/ml
Who cannot join
- concomitant or sporadic use of NSAID, corticosteroids or other immune modulating therapies including interferon-alpha
- cholesterol > 7 M
- under treatment for hypertension or antihypertensive treatment indicated at inclusion
- cardiovascular events or stroke in parents, siblings or off-springs occurring < 55 years of age
- elevated serum creatinine
- diabetes type I or II
Show all 16Show fewer
- known hypersensitivity for etoricoxib, capsule substances or sulphonamides
- active peptic ulcer or gastrointestinal haemorrhage
- history of asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic reactions after taking acetyl salicylic acid or NSAID including COX-2 inhibitors
- pregnancy or insufficient birth control for females
- breastfeeding
- seriously deranged liver function
- creatine clearance < 30 ml/min
- inflammatory bowel disease
- heart failure (NYHA II-IV)
- established ischaemic heart disease, peripheral arteriosclerosis and/or cerebrovascular disease
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
Department of Infectious Diseases, Oslo University Hospital
Oslo, 0407
The Biotechnology Centre, University of Oslo
Oslo, 0407
About this study
Official title: Optional Immunomodulating Therapy and Improved Vaccination Responses by Adjuvant Administration of a Cyclooxygenase Type 2 Inhibitor in Antiretroviral naïve HIV-infected Patients and Patients on ART
Chronic immune activation is a central feature of HIV-infection, and the degree of activated T-cells is a better predictor of disease progression and mortality than plasma viral load. The study hypothesis is that the anti-inflammatory substance etoricoxib will dampen chronic immune activation and improve the effect of T-cell dependent vaccines in HIV-1 infected patients.
The aim of the present study is to explore the efficacy of the study drug on markers of immune activation and vaccine responses, as well as safety of the study drug, in HIV-infected patients not receiving antiretroviral therapy and in patients on long-term effective ART who had CD4 counts < 500.
Read the detailed description
The current trial was based on our observations that augmented levels of cyclic adenosine monophosphate (cAMP) contribute to the T cell dysfunction in HIV-infected patients. In T cells, cAMP triggers a protein kinase A (PKA) - Csk - Lck inhibitory pathway that inhibits the proximal T cell receptor (TCR) signaling events. This mechanism may also be involved in the inhibitory function of regulatory T cells.
The investigators have hypothesized that elevated levels of cAMP in T cells from HIV-infected individuals result from increased production of prostaglandin E2 (PGE2) following activation-induced expression of cyclooxygenase type 2 (COX-2) in lymphoid tissues. Although the investigators have identified even COX-2 positive T cells in HIV-infected individuals, activated monocytes may be the major source of PGE2; high levels of COX-2 are produced de novo after a number of stimuli, particularly lipopolysaccharide (LPS). Circulating LPS is indeed increased in untreated chronic HIV infection due to enhanced translocation of microbial material and correlates to chronic immune activation and disease progression.
In three preceding clinical explorative trials, the investigators have demonstrated that COX-2 inhibition by COX-2 inhibitors (COX-2i) improves the immune functions of HIV patients, the first two studies included patients on antiretroviral treatment (ART). In the third trial the investigators also showed for the first time that treatment with a COX-2i was able to downregulate chronic immune activation and improve T cell functions (efficacy of T cell-dependent vaccine) in asymptomatic HIV-infected patients who did not use ART. In these patients, chronic immune activation was dampened as demonstrated; CD38 density on CD8+ T cells (primary endpoint) decreased by 24% by study week 12. This reduction could be extrapolated to a possible improvement of CD4+ T cell loss with 30 CD4 cells per ul per year with an approximate mean CD4 loss of 60 per ul per year. These data founded the basis for further support to this study through the GLOBVAC call program under the Norwegian Research Council (granted application for the current study).
- Conditions
- HIV
- Being tested
- Etoricoxib
- Keywords
- Cox-2 inhibitor, HIV, immune activation, immune modulating, progression markers, vaccine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtoricoxibDrug
Also called Arcoxia
90 mg QD
| Study group | Role | What they receive |
|---|---|---|
| Etoricoxib 90 mg qd for 25 weeks ART- | Active comparator | Etoricoxib for 25 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 5 weeks. Receives: Drug: Etoricoxib |
| Etoricoxib 90 mg qd for 2 weeks ART- | Active comparator | Etoricoxib for 2 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week. Receives: Drug: Etoricoxib |
| Control ART- | No intervention | No Etoricoxib. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week. |
| Etoricoxib 90 mg qd for 25 weeks ART+ | Active comparator | Etoricoxib for 25 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 5 weeks. Receives: Drug: Etoricoxib |
| Etoricoxib 90 mg qd for 2 weeks ART+ | Active comparator | Etoricoxib for 2 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week. Receives: Drug: Etoricoxib |
| Control ART+ | No intervention | No Etoricoxib. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in progression markers and vaccine responses within and between ART groups
Changes in CD38 density (CD38 molecules per CD38+CD8+CD3+ T cells) and in humoral and cellular immune responses to study-specific vaccines.
Measured: After 6 months
Serious adverse events
Reductions of etoricoxib dose or stop of drug, adverse events including cardiovascular events, blood pressure, clinical chemistry.
Measured: During the 6 months study period
Secondary outcomes (2)
Changes in HIV Gag CD8+ T cell responses within and between ART groups
Changes in HIV Gag CD8+ T cell responses within and between ART groups
Measured: 6 months
Changes in plasma markers of inflammation, coagulation and tryptophan metabolism within and between ART groups
Changes in plasma markers of inflammation, coagulation and tryptophan metabolism
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2011 (estimated)
- Study startOct 2010
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dag Kvale
- Sponsor type
- University, hospital or other
- Collaborators
- The Research Council of Norway
- Responsible party
- Sponsor-investigator, Dag Kvale, Oslo University Hospital
- Investigators
- Dag Kvale, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01269515
- Sponsor's protocol ID
- OUSCOX2
- Acronym
- OUSCOX2
- Status last verified
- May 2017
- First submitted
- 3 Jan 2011
- Last updated
- 31 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Prebensen C, Troseid M, Ueland T, Dahm A, Sandset PM, Aaberge I, Waalen K, Dyrhol-Riise AM, Tasken K, Kvale D. Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial. PLoS One. 2017 May 2;12(5):e0176527. doi: 10.1371/journal.pone.0176527. eCollection 2017.
PubMed 28464042
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optional Immunomodulating Therapy and Improved Vaccination Responses by Adjuvant Administration of a Cyclooxygenase Type 2 Inhibitor in Antiretroviral naïve HIV-infected Patients and Patients on ART
- ClinicalTrials.gov ID
- NCT01269515
- Acronym / sponsor ID
- OUSCOX2 / OUSCOX2
- Conditions
- HIV
- Keywords
- Cox-2 inhibitor, HIV, immune activation, immune modulating, progression markers, vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Dag KvaleUniversity, hospital or other
- Collaborators
- The Research Council of Norway
- Study start
- Oct 2010
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 4 Jan 2011 (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.
Chronic immune activation is a central feature of HIV-infection, and the degree of activated T-cells is a better predictor of disease progression and mortality than plasma viral load. The study hypothesis is that the anti-inflammatory substance etoricoxib will dampen chronic immune activation and improve the effect of T-cell dependent vaccines in HIV-1 infected patients.
The aim of the present study is to explore the efficacy of the study drug on markers of immune activation and vaccine responses, as well as safety of the study drug, in HIV-infected patients not receiving antiretroviral therapy and in patients on long-term effective ART who had CD4 counts < 500.
Detailed description
The current trial was based on our observations that augmented levels of cyclic adenosine monophosphate (cAMP) contribute to the T cell dysfunction in HIV-infected patients. In T cells, cAMP triggers a protein kinase A (PKA) - Csk - Lck inhibitory pathway that inhibits the proximal T cell receptor (TCR) signaling events. This mechanism may also be involved in the inhibitory function of regulatory T cells.
The investigators have hypothesized that elevated levels of cAMP in T cells from HIV-infected individuals result from increased production of prostaglandin E2 (PGE2) following activation-induced expression of cyclooxygenase type 2 (COX-2) in lymphoid tissues. Although the investigators have identified even COX-2 positive T cells in HIV-infected individuals, activated monocytes may be the major source of PGE2; high levels of COX-2 are produced de novo after a number of stimuli, particularly lipopolysaccharide (LPS). Circulating LPS is indeed increased in untreated chronic HIV infection due to enhanced translocation of microbial material and correlates to chronic immune activation and disease progression.
In three preceding clinical explorative trials, the investigators have demonstrated that COX-2 inhibition by COX-2 inhibitors (COX-2i) improves the immune functions of HIV patients, the first two studies included patients on antiretroviral treatment (ART). In the third trial the investigators also showed for the first time that treatment with a COX-2i was able to downregulate chronic immune activation and improve T cell functions (efficacy of T cell-dependent vaccine) in asymptomatic HIV-infected patients who did not use ART. In these patients, chronic immune activation was dampened as demonstrated; CD38 density on CD8+ T cells (primary endpoint) decreased by 24% by study week 12. This reduction could be extrapolated to a possible improvement of CD4+ T cell loss with 30 CD4 cells per ul per year with an approximate mean CD4 loss of 60 per ul per year. These data founded the basis for further support to this study through the GLOBVAC call program under the Norwegian Research Council (granted application for the current study).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Etoricoxib 90 mg qd for 25 weeks ART- | Active comparator | Drug: EtoricoxibEtoricoxib for 25 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 5 weeks. |
| Etoricoxib 90 mg qd for 2 weeks ART- | Active comparator | Drug: EtoricoxibEtoricoxib for 2 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week. |
| Control ART- | No intervention | –No Etoricoxib. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week. |
| Etoricoxib 90 mg qd for 25 weeks ART+ | Active comparator | Drug: EtoricoxibEtoricoxib for 25 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 5 weeks. |
| Etoricoxib 90 mg qd for 2 weeks ART+ | Active comparator | Drug: EtoricoxibEtoricoxib for 2 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week. |
| Control ART+ | No intervention | –No Etoricoxib. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ART- group: Confirmed diagnosis of HIV infection < 8 years prestudy
- no HIV-related clinical manifestations including acute HIV infection
- no current indication or use for antiretroviral treatment
- CD4+ count > 350 x 10^6 /l
- HIV RNA > 2000 copies/ml
Key exclusion criteria (16 listed)
- concomitant or sporadic use of NSAID, corticosteroids or other immune modulating therapies including interferon-alpha
- cholesterol > 7 M
- under treatment for hypertension or antihypertensive treatment indicated at inclusion
- cardiovascular events or stroke in parents, siblings or off-springs occurring < 55 years of age
- elevated serum creatinine
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 |
|---|---|---|
| EtoricoxibAlso: Arcoxia90 mg QD | Drug | Etoricoxib 90 mg qd for 2 weeks ART+, Etoricoxib 90 mg qd for 2 weeks ART-, Etoricoxib 90 mg qd for 25 weeks ART+, Etoricoxib 90 mg qd for 25 weeks ART- |
Primary outcome
Changes in progression markers and vaccine responses within and between ART groups
Time frame: After 6 months
Changes in CD38 density (CD38 molecules per CD38+CD8+CD3+ T cells) and in humoral and cellular immune responses to study-specific vaccines.
Serious adverse events
Time frame: During the 6 months study period
Reductions of etoricoxib dose or stop of drug, adverse events including cardiovascular events, blood pressure, clinical chemistry.
2 secondary outcomes
Changes in HIV Gag CD8+ T cell responses within and between ART groups
Time frame: 6 months
Changes in plasma markers of inflammation, coagulation and tryptophan metabolism within and between ART groups
Time frame: 6 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 31 May 2017.
- Results publication: PubMed 28464042Prebensen C, Troseid M, Ueland T, Dahm A, Sandset PM, Aaberge I, Waalen K, Dyrhol-Riise AM, Tasken K, Kvale D. Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial. PLoS One. 2017 May 2;12(5):e0176527. doi: 10.1371/journal.pone.0176527. eCollection 2017.
- Individual participant dataSharing planned: No
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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.
Dag Kvale, MD, PhD principal investigator
Oslo University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etoricoxib in people with HIV, run by Dag Kvale at 2 sites in Norway.
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 10 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 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. 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?
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?
Changes in progression markers and vaccine responses within and between ART groups (time frame: After 6 months). The study lists 2 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 NCT01269515, 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 31 May 2017.