Changes in Cerebral Function in Treatment Naive HIV-1 Infected Subjects Commencing Either Boosted Atazanavir With Truvada or Boosted Darunavir With Maraviroc and Kivexa (CogUK)

This study is currently recruiting participants.
Verified April 2013 by Imperial College London
Sponsor:
Collaborators:
Cheif Investigator: Alan Winston
collaborators: Pfizer
Information provided by (Responsible Party):
Naomi Gardner, Imperial College London
ClinicalTrials.gov Identifier:
NCT01367236
First received: June 3, 2011
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to compare two different combination anti-HIV therapies over 48 weeks and to assess if differences in improvement in the function of the brain are observed over this period.

The study will compare anti-HIV therapy combinations which are currently in use.

The patients will not have had any previous treatment for their HIV infection.


Condition Intervention Phase
HIV
Impaired Cognition
Drug: standard care
Drug: novel treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised, Prospective Study, Assessing Changes in Cerebral Function in Treatment Naive HIV-1 Infected Subjects Commencing Either Boosted Atazanavir With Truvada or Boosted Darunavir With Maraviroc and Kivexa.

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • cognitive function [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    When commencing antiretroviral therapy (anti-HIV therapy) for the first time, improvements in the function of the brain are frequently observed. For example memory and concentration may improve. However, whether these improvements may differ between different anti-HIV therapies is largely unknown.

    The purpose of this study is to compare two different combination anti-HIV therapies over 48 weeks and to assess if differences in improvement in the function of the brain are observed over this period.



Secondary Outcome Measures:
  • brain function [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    The study team will assess the brain functions at each visit. Also the blood will be monitored for efficacy of treatment in the two study limbs at all visits (this is part of normal care). Likewise the results of the MRI scans will be compared. The lumbar puncture performed at the final visit will obtain samples of CSF and certain test will be performed on this to examine the differences between the two study treatments. The comparison of the scan and lumbar puncture results will indicate how the brain is differently effected with different treatments.


Estimated Enrollment: 50
Study Start Date: January 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: standard care

treatment with:

  • atazanavir 300 mg daily
  • ritonavir 100 mg daily
  • tenofovir 245 mg daily*
  • emtricitabine 200 mg daily* * as the fixed dose combination Truvada™
Drug: standard care
  • atazanavir 300 mg daily
  • ritonavir 100 mg daily
  • tenofovir 245 mg daily*
  • emtricitabine 200 mg daily*
Active Comparator: Novel therapeutic approach
  • darunavir 800 mg daily
  • ritonavir 100 mg daily
  • lamivudine 300 mg daily**
  • abacavir 600 mg daily**
  • maraviroc 150 mg once daily ** as the fixed dose combination Kivexa ™
Drug: novel treatment
  • darunavir 800 mg daily
  • ritonavir 100 mg daily
  • lamivudine 300 mg daily** and abacavir 600mgs daily**
  • maraviroc 150 mg once daily

Detailed Description:

Impairment in neurocognitive(NC) function in HIV-infected subjects in the current anti-retroviraltreatment (cART) era has been associated with poor compliance with cART, reduced quality-of-life and increased mortality. Reported factors associated with the development of NC function impairment in HIV disease and risks associated with progression of such impairment include degree of immune suppression related to HIV infection, other chronic viral infections (such as chronic hepatitis C co-infection), age and central nervous system (CNS) antiretroviral drug exposure.

One modifiable factor which may be associated with the evolution of NC function impairment is the direct effect of cART on the central-nervous-system (CNS). Certain antiretroviral drugs such as zidovudine, lamivudine, abacavir, nevirapine, efavirenz and indinavir are known to achieve optimal exposure in the cerebro-spinal-fluid (CSF) whereas other drugs, such as the majority of the HIV-1 protease inhibitors penetrate less effectively. Studies to date suggest different cART regimens may have differing effects on NC performance. In the EuroSIDA study, the use of nucleoside-reverse-transcriptase inhibitors was found to specifically protect against the development of HIV related brain disease. More recently, in a small prospective study, ALTAIR, different effect on cerebral function was reported in subjects randomised to commence three different cART regimens.

The investigators propose, in a prospective, randomised study to assess the effects of two different antiretroviral regimens on NC function in HIV infected subjects commencing antiretroviral therapy for the first time.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected males or females
  • signed informed consent
  • no previous antiretroviral treatment since HIV diagnosis
  • screening CD4+ lymphocyte count <= 350 cells/ųL
  • susceptible to all currently licensed (Nucleoside Reverse Transcriptase Inhibitors) NRTIs, (Non-Nucleoside Reverse Transcriptase Inhibitors) NNRTIs and PIs based on HIV-1 genotypic resistance report
  • CCR5-tropic HIV based on genotypic resistance testing*

Exclusion Criteria:

  • • existing neurological disease

    • hepatitis B or hepatitis C co-infection
    • age under 18 years
    • screening laboratory parameters > grade 2 (with the exception of cholesterol and triglycerides)
    • current history of major depression or psychosis
    • recent head injury (past three months)
    • current alcohol abuse or drug dependence
    • active opportunistic infection or significant co-morbidities
    • patients who are receiving other concomitant medication which are not permitted, as listed in appendix 2
    • female patients of child-bearing potential who:

      • have a positive serum pregnancy test at screening or during the study
      • are breast feeding
      • are planning to become pregnant
    • all participants unwilling to use a barrier method of contraception
    • patients who in the opinion of the investigator are not candidates for inclusion in the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01367236

Contacts
Contact: Andrew Whitehouse, MBBS 02075943413 a.whitehouse@imperial.ac.uk
Contact: Alan Winston, MD a.winston@imperial.ac.uk

Locations
United Kingdom
Birmingham Heartlands Hospital: Recruiting
Birmingham, United Kingdom
Principal Investigator: Steve Taylor, FRCP         
Brighton and Sussex University Hospital NHS Trust: Recruiting
Brighton, United Kingdom, BN1 9RE
Principal Investigator: Martin Fisher, FRCP         
Chelsea and Westminster Hospital NHS Trust Recruiting
London, United Kingdom, SW10 9NH
Principal Investigator: Mark Nelson, FRCP         
St. Thomas' Hospital Recruiting
London, United Kingdom
Principal Investigator: Ranjababu Kulasegaram, MD         
Kings College Hospital Recruiting
London, United Kingdom, SE5 9RJ
Principal Investigator: Frank Post, MD PhD         
St. Mary's Hospital Recruiting
London:, United Kingdom, W2 1NY
Principal Investigator: Alan Winston, MD         
Sponsors and Collaborators
Imperial College London
Cheif Investigator: Alan Winston
collaborators: Pfizer
  More Information

No publications provided

Responsible Party: Naomi Gardner, PRS Administrator, Imperial College London
ClinicalTrials.gov Identifier: NCT01367236     History of Changes
Other Study ID Numbers: 1733, 2011-002656-14
Study First Received: June 3, 2011
Last Updated: April 3, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
HIV Protease Inhibitors
Anti-HIV Agents
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Atazanavir
Darunavir
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014