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Completed

NCT Number: NCT01451333

The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1

Persistent HIV infection in the central nervous system (CNS) compartment may put subjects at risk of developing HIV-related brain disease. Important factors associated with the development of HIV-related brain disease include therapeutic concentrations of antiretroviral drugs in the CNS. Conflicting evidence regarding the CNS exposure of the antiretroviral drug used for the encore1 study, efavirenz (EFV) have been described in related studies. There were recent study of two small series assessment of EFV exposure in the cerebral spinal fluid (CSF); one group reported small detectable EFV concentrations, while another observed undetectable EFV exposure in the CSF. Also, in a larger reported series comprising of 80 subjects on EFV-containing antiretroviral therapy, a CSF to plasma concentration suggested that there is limited movement of EFV out of the CSF. In HIV-1 infected subjects at steady state, EFV plasma level parameters are dose proportional following 200mg, 400mg, and 600mg daily doses. The CNS exposure of EFV at different daily dosing has not been described.

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Key information

Conditions

HIV Infection Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Medical Group Practice, Berlin, State of Berlin, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.

Exclusion criteria

  • Existing neurological disease which in the opinion of the investigator would be a contra-indication to lumbar puncture examination
  • CNS opportunistic infections in the past 12 weeks of randomisation
  • Bacterial or viral meningitis in the past 12 weeks of randomisation
  • Head injury requiring medical assessment in the past 12 weeks of randomisation

Treatment and study plan

Efavirenz

Drug

600mg qd; 3 x 200mg qd

Primary outcomes

  1. comparison of mean CSF concentration of EFV from both doses after week 24.

    Time frame: 24 weeks

    measure the CSF exposure of EFV when dosed at 400mg and 600mg daily. Efavirenz plasma and CSF concentrations will be analysed and CSF:plasma ratios will be compared. Associations between plasma and CSF concentrations and relationship to study clinical parameters will be assessed.

Secondary outcomes

  1. CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis

    Time frame: 24 weeks

    The relationship between CSF EFV exposure and plasma exposure (CSF:plasma ratio), both for protein bound and free plasma EFV exposure.

  2. The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments

    Time frame: 24 weeks

  3. The relationship between CSF EFV exposure and other study parameters such as race and sex.

    Time frame: 24 weeks

  4. The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL)

    Time frame: 24 weeks

  5. CSF HIV RNA measurement after 12 - 24 weeks of study therapy

    Time frame: 24 weeks

  6. Relationship between plasma HIV RNA and CSF HIV RNA

    Time frame: 24 weeks

  7. CSF biomarker analysis after 12 - 24 weeks of study therapy

    Time frame: 24 weeks

  8. comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration

    Time frame: 24 weeks

Sponsors and collaborators

Lead sponsor

Kirby Institute

Other Gov

Collaborators

  • Imperial College London

Registry information

Official study title

The EFV Central Nervous System Exposure Sub-study of Encore1: A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals Over 96 Weeks

Acronym: ENCORE1-CNS

Important dates

Study start
2011
Primary completion
2012
Study completion
2013
First posted
Oct 13, 2011
Registry last updated
May 13, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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