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

NCT01269515 | Completed Phase 2

• 1 other identifier: OUSCOX2
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

HIV

Keywords

Cox-2 inhibitor; HIV; immune activation; immune modulating; progression markers; vaccine

Outcome Measures

Primary Outcomes (2)

• 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.

  After 6 months

• Serious adverse events

  Reductions of etoricoxib dose or stop of drug, adverse events including cardiovascular events, blood pressure, clinical chemistry.

  During the 6 months study period

Secondary Outcomes (2)

• Changes in HIV Gag CD8+ T cell responses within and between ART groups

  6 months

• Changes in plasma markers of inflammation, coagulation and tryptophan metabolism within and between ART groups

  6 months

Study Arms (6)

Etoricoxib 90 mg qd for 25 weeks ART-

ACTIVE COMPARATOR

Etoricoxib for 25 weeks. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 5 weeks.

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.

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.

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.

Drug: Etoricoxib

Control ART+

NO INTERVENTION

No Etoricoxib. Vaccination (Tetanus Toxoid, conjugated pneumococcal, seasonal influenza) after 1 week.

Interventions

Etoricoxib DRUG

90 mg QD

Also known as: Arcoxia

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-

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• concomitant or sporadic use of NSAID, corticosteroids or other immune modulating therapies including interferon-alpha
• cholesterol \> 7 M
• 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

Sponsors & Collaborators

• Dag Kvale: lead
• The Research Council of Norway: collaborator

Study Sites (2)

Department of Infectious Diseases, Oslo University Hospital

Oslo, 0407, Norway

Location

The Biotechnology Centre, University of Oslo

Oslo, 0407, Norway

Location

Related Publications (1)

• 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.

  PMID: 28464042 RESULT

MeSH Terms

Interventions

Etoricoxib

Intervention Hierarchy (Ancestors)

Sulfones; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dag Kvale, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Senior consultant

Study Record Dates

• First Submitted: January 3, 2011
• First Posted: January 4, 2011
• Study Start: October 1, 2010
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: May 31, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2)