Immunomodulating Therapy and Improved Vaccination Responses by Cox-2 Inhibitor in HIV-infected Patients (OUSCOX2)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by Oslo University Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
The Research Council of Norway
Information provided by (Responsible Party):
Dag Kvale, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT01269515
First received: January 3, 2011
Last updated: May 11, 2012
Last verified: May 2012

January 3, 2011
May 11, 2012
October 2010
December 2012   (final data collection date for primary outcome measure)
  • Changes in progression markers and vaccine responses [ Time Frame: After 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Reductions of etoricoxib dose or stop of drug, adverse events including cardiovascular events, blood pressure, clinical chemistry.
Same as current
Complete list of historical versions of study NCT01269515 on ClinicalTrials.gov Archive Site
  • Changes in progression markers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Changes in CD38 density (molecules/cell) in CD8+PD-1+ or other T cell subsets, CD4+ T cell counts, HIV RNA, immunoglobulin levels, β2-microglobulin, CRP, D-dimer.
  • Clinical events [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    HIV-related clinical events, Indication for antiretroviral treatment.
Same as current
Not Provided
Not Provided
 
Immunomodulating Therapy and Improved Vaccination Responses by Cox-2 Inhibitor in HIV-infected Patients
Optional Immunomodulating Therapy and Improved Vaccination Responses by Adjuvant Administration of a Cyclooxygenase Type 2 Inhibitor in Antiretroviral naïve HIV-infected Patients

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.

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).

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
Drug: Etoricoxib
90 mg QD
Other Name: Arcoxia
  • Active Comparator: Etoricoxib 90 mg qd for 25 weeks
    Etoricoxib for 25 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 5 weeks.
    Intervention: Drug: Etoricoxib
  • Active Comparator: Etoricoxib 90 mg qd for 2 weeks
    Etoricoxib for 2 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week.
    Intervention: Drug: Etoricoxib
  • No Intervention: Control
    No Etoricoxib. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
December 2012
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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 106 /l
  • HIV RNA > 2000 copies/ml

Exclusion Criteria:

  • On current antiretroviral treatment
  • 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
  • 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
Both
18 Years to 65 Years
No
Norway
 
NCT01269515
OUSCOX2
No
Dag Kvale, Oslo University Hospital
Dag Kvale
The Research Council of Norway
Principal Investigator: Dag Kvale, MD, PhD Oslo University Hospital
Oslo University Hospital
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP