Condition category
Infections and Infestations
Date applied
02/02/2011
Date assigned
18/04/2011
Last edited
19/06/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Despite a sharp decrease in human immunodeficiency virus (HIV)-associated dementia with the use of combined antiretroviral drugs, there is a high prevalence of mild or moderate neurocognitive disorders in patients receiving antiretroviral treatment. A low level viral activity may persist in the central nervous system even in those patients presenting undetectable viral load, leading to local inflammation, neuronal damage and neurocognitive impairment. The aim of this study is to find out whether switching from a first-line antiretroviral treatment to a combination with a higher penetration to the central nervous system could reduce inflammation and neurocognitive impairment

Who can participate?
HIV-positive adults aged over 18 on efavirenz/tenofovir/emtricitabine treatment for at least 24 weeks, undetectable HIV viral load in the last 24 weeks, and neurocognitive impairment.

What does the study involve?
Patients will be switched from emtricitabine/tenofovir/efavirenz once daily to lamivudine/abacavir once daily and maraviroc twice daily. A neuropsychological test will be performed at weeks 0 and 48, and a lumbar puncture at weeks 0 and 24. Every patient will continue with routine visits every 3 - 4 months.

What are the possible benefits and risks of participating?
The use of a combination treatment with better penetration into the brain could reduce neuronal damage and inflammation and improve neurocognitive impairment. Risks of taking part include the side effects associated with the new medications.

Where is the study run from?
Institute of Biomedical Investigations of Bellvitge (Spain).

When is the study starting and how long is it expected to run for?
The study ran from January 2011 to July 2013.

Who is funding the study?
ViiV Healthcare (UK).

Who is the main contact?
Dr Daniel Podzamczer

Trial website

Contact information

Type

Scientific

Primary contact

Dr Daniel Podzamczer

ORCID ID

Contact details

c/Feixa Llarga s/n. L'Hospitalet
Barcelona
08907
Spain

Additional identifiers

EudraCT number

2010-022202-41

ClinicalTrials.gov number

Protocol/serial number

2010-022202-41

Study information

Scientific title

Switching from efavirenz/tenofovir/emtricitabine (TDF/FTC/EFV) to abacavir/lamivudine/maraviroc (ABC/3TC/MVC) to assess antiretroviral activity in cerebrospinal fluid: a prospective one-arm pilot study

Acronym

MRVstudy-10 (XUMAKER)

Study hypothesis

Change to a regimen with greater cerebrospinal fluid (CSF) penetration will be associated with a lower CSF viral load, a decrease in inflammatory markers and possibly with an improvement in neurocognitive tests.

On 19/06/2014 the following changes were made to the trial record:
1. The public title was changed from 'Switching from efavirenz/tenofovir/emtricitabine (TDF/FTC/EFV) to abacavir/lamivudine/nevirapine (ABC/3TC/NVP) to assess antiretroviral activity in cerebrospinal fluid' to 'Switching from efavirenz/tenofovir/emtricitabine (TDF/FTC/EFV) to abacavir/lamivudine/maraviroc (ABC/3TC/MVC) to assess antiretroviral activity in cerebrospinal fluid'
2. The scientific title was changed from 'Switching from efavirenz/tenofovir/emtricitabine (TDF/FTC/EFV) to abacavir/lamivudine/nevirapine (ABC/3TC/NVP) to assess antiretroviral activity in cerebrospinal fluid: a prospective one arm pilot study' to 'Switching from efavirenz/tenofovir/emtricitabine (TDF/FTC/EFV) to abacavir/lamivudine/maraviroc (ABC/3TC/MVC) to assess antiretroviral activity in cerebrospinal fluid: a prospective one-arm pilot study'
3. The anticipated end date was changed from 01/04/2012 to 01/07/2013

Ethics approval

University Hospital of Bellvitge, Barcleona [CEIC Hospital Universitari de Bellvitge, Barcelona] (Spain), 07/10/2010

Study design

Prospective one-arm pilot study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Human immunodeficiency virus (HIV)

Intervention

Current interventions as of 19/06/2014:
1. This is a single-arm study. Patients presenting confirmed neurocognitive impairment, with documented CCR5+ viral tropism, will be switched from emtricitabine 200 mg/tenofovir 245 mg/efavirenz 600 mg once daily (OD) to lamivudine 300 mg/abacavir 600 mg OD and maraviroc 300 mg twice daily (BID)
2. A neuropsychological test will be performed at weeks 0 and 48, and a lumbar puncture at weeks 0 and 24
3. Every patient will continue with routine visits every 3 - 4 months

Previous interventions:
1. This is a single-arm study; all diagnosed of neuropsychological impairment, CCR5+ patients will be switched from emtricitabine 200 mg/tenofovir 245 mg/efavirenz 600 mg four times daily (QD) to lamivudine 300 mg/abacavir 600 mg QD and maraviroc 300 mg twice daily (BID).
2. A neuropsychological test will be performed at weeks 0, 24 and 48, and a lumbar puncture at weeks 0 and 48
3. Every patient will continue his/her routine control every 3 - 4 months

Intervention type

Drug

Phase

Phase IV

Drug names

Current drugs as of 19/06/2014:
1. Efavirenz/tenofovir/emtricitabine (TDF/FTC/EFV)
2. Abacavir/lamivudine/maraviroc (ABC/3TC/MVC)

Previous drugs:
1. Efavirenz/tenofovir/emtricitabine (TDF/FTC/EFV)
2. Abacavir/lamivudine/nevirapine (ABC/3TC/NVP)

Primary outcome measures

Viral load (VL) less than 5 copies/ml in CSF, evaluated at week 48

Secondary outcome measures

Evaluated at week 48:
1. Viral load (VL) less than 50 copies/ml in CSF
2. Central nervous system (CNS) inflammatory markers change in CSF
3. Neurocognitive tests

Overall trial start date

27/01/2011

Overall trial end date

01/07/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Human immunodeficiency virus positive (HIV+)
2. Adults aged over 18 years
3. HLA-B*57:01:01 negative
4. On TDF/FTC/EFV treatment for at least 24 weeks and undetectable HIV viral load in the last 24 weeks
5. Neurocognitive impairment
6. CCR5+ (pro-viral deoxyribonucleic acid [DNA])
7. Signed informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

15

Participant exclusion criteria

1. Alanine aminotransferase (ALT) greater than 5 fold upper normal limit
2. Renal impairment (creatinine clearance [Cl cr] less than 50 ml/min)
3. Haemoglobin less than 9 g/dl
4. Neutropenia (PMN) less than 1000/ml
5. Platelets less than 30,000/mm3
6. Opportunistic infection, cancer and /or any disease which could alter blood brain barrier permeability (meningitis, cancer, etc.)
7. Neuro-psychiatric disease (previous or current)
8. Illicit drugs use

Recruitment start date

27/01/2011

Recruitment end date

01/07/2013

Locations

Countries of recruitment

Spain

Trial participating centre

c/Feixa Llarga s/n. L'Hospitalet
Barcelona
08907
Spain

Sponsor information

Organisation

Institute of Biomedical Investigations of Bellvitge [Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)] (Spain)

Sponsor details

c/o Daniel Podzamczer PhD
c/Feixa Llarga s/n
L'Hospitalet de Llobregat
Barcelona
08907
Spain

Sponsor type

Research organisation

Website

http://www.bellvitgehospital.cat/

Funders

Funder type

Industry

Funder name

ViiV Healthcare (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes