Condition category
Infections and Infestations
Date applied
16/08/2012
Date assigned
16/08/2012
Last edited
21/05/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Recent studies have suggested that some HIV-infected patients experience mild problems with 'cognitive impairment'. Mild cognitive impairment means a slight slowing of brain processes, which could lead to problems with memory or concentration. Currently it is not fully understood why these problems occur or what we may be able to do to improve them. In particular it is not known what role anti-retroviral medications (anti-HIV drugs) may have in affecting brain function, and whether certain anti-retroviral drugs may lead to a greater tendency to develop problems, or whether some may be better than others at preventing the problems. Efavirenz (EFV) is currently one of the most commonly used anti-retroviral drugs. It is also known as Sustiva® and is a component of Atripla®. We know that Efavirenz can have effects on the brain in the first few weeks of treatment such as bad dreams and dizziness, but these usually settle. However, recent research suggests that Efavirenz may have some longer term effect on brain function (although this does not appear to be very severe in the vast majority of cases). This study aims to find out whether switching treatment away from Efavirenz to another anti-retroviral medication (Kaletra®) may improve brain function. Kaletra® is another commonly used anti-retroviral medication and does not appear to have the same potential effect on brain function.

Who can participate?
Patients infected with HIV-1 who are 18 years old or over and are receiving a highly active anti-retroviral therapy (HAART) combination which contains efavirenz, and have a suppressed HIV viral load.

What does the study involve?
We will switch your medication from Efavirenz to Kaletra® for 12 weeks, and look for any change in brain function. We will make measurements at the beginning and end of the study to see how they change. These will include: a special kind of MRI scan, which measures chemicals in the brain, a computerised test of brain function ('memory games'), sleep diaries and blood tests. If impairment in brain function is due to Efavirenz use, this may change and possibly improve on switching to Kaletra. This is a pilot study and therefore any changes seen would need to be confirmed in further studies. There is a possibility that there will be no significant changes and no improvement or change in brain function that is detectable.

What are the possible benefits and risks of participating?
The main purpose of the study is to better understand the effect of different anti-retroviral drugs on brain function in HIV infection to help clinicians guide treatment choices in the future. It is possible that patients may see an improvement in their cognitive function (e.g. memory or concentration) and quality of sleep; however, this may not be solely due to the study drug. Both Efavirenz and Kaletra® are licensed for treatment of HIV infection and they are considered to be equally effective. There is therefore a negligible risk of virological failure (rise in HIV viral load) from a switch to Kaletra®. Patients’ viral load will be monitored for any problems during the study. Kaletra® is a commonly used anti-retroviral medication and has been shown to be safe and well-tolerated in large clinical trials. There are possible side effects associated with taking Kaletra®; these include nausea and a slightly higher rate of diarrhoea compared with Efavirenz. If these do occur they are usually mild. The rate of serious adverse events with Kaletra has been shown to be low. Some patients also show increases in levels of cholesterol and triglycerides on their blood tests. These changes would not be expected to lead to any problems within the short duration of this study. The blood tests will be monitored regularly to check for any problems during the study.

Where is the study run from?
The study will be run by the Clinical Research Facility which is designed specifically for conducting clinical trials at Royal Victoria Infirmary Newcastle (UK).

When is the study starting and how long is it expected to run for?
The study started in October 2012 and will run for two years and six months. Each patient will participate in the study for 15 weeks.

Who is funding the study?
This study is funded by a research grant from Abbott Laboratories Limited. They are also providing the study drug Kaletra® at no cost for the duration of the study. Abbott is the company who is licensed to sell Kaletra in the UK at present. Abbott has no role in the design or running of the study or ownership of the data. The Newcastle Clinical Trials Unit is managing the study. The Newcastle upon Tyne Hospitals NHS Foundation Trust is the legal sponsor of the study.

Who is the main contact?
Dr Ashley Price (Chief Investigator), david.price@nuth.nhs.uk
Ann Marie Hynes (Trial Manager), ann.hynes@newcastle.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ann Marie Hynes

ORCID ID

Contact details

Newcastle Clinical Trials Unit
Institute of Health and Society
4th Floor
William Leech Building
Framlington Place
Newcastle Upon Tyne
NE2 4HH
United Kingdom
+44 (0)191 2087187
ann.hynes@ncl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

12779

Study information

Scientific title

Efficacy of Switch to Lopinavir/Ritonavir in Improving Cognitive function in Efavirenz treated patients

Acronym

SLICE

Study hypothesis

Efavirenz (EFV) is currently one of the most commonly used anti-retroviral drugs. It is well recognised that cognitive side-effects are common in the first 4-6 weeks of EFV therapy and it is thought that these effects disappear entirely after treatment, however recent data suggests that EFV may have long-term detrimental effects in brain function.

Recent research studies have suggested that many HIV-infected patients experience mild problems with 'cognitive function'. This means that there may be slight slowing of brain processes and this may lead to problems with memory or concentration. These problems tend to be mild, but may potentially have an impact on daily life. We currently do not know why these problems occur or what we may be able to do to improve them. In particular we do not know what role anti-retroviral medications have in brain function and whether certain antiretroviral drugs may lead to a greater tendency to develop problems or may be better than others at preventing the problems.

We are investigating whether a commonly used anti-retroviral medication (Efavirenz) has an adverse effect on brain function and whether this can be improved by a switch to another drug (Kaletra®).

More details can be found here: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12779

On 21/05/2015 the following changes were made to the trial record:
1. The overall trial start date was changed from 01/09/2012 to 01/11/2012.
2. The overall trial end date was changed from 01/09/2014 to 31/12/2015.

Ethics approval

NRES Committee North East - Newcastle & North Tyneside 2, 11/06/2012, ref: 12/NE/0071

Study design

Non-randomised interventional study

Primary study design

Interventional

Secondary study design

Non randomised study

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

Infectious diseases and microbiology

Intervention

Switching from EFV to Kaletra, This is an exploratory single-centre, self-controlled, open-label phase IV pilot study, comparing the efficacy of Efavirenz (EFV) and Kaletra on neurocognitive performance.

All subjects will switch from EFV to Kaletra.
30 subjects will be recruited in total.

Study duration will be 15 weeks from baseline visit (week 1). Each participant will be required to take the study drug for 12 weeks. For the first 2 weeks participants will stay on EFV and complete the first sleep diary and will have baseline cognitive testing and MR scan. At week 3 they will then switch to the study drug (Kaletra). 4 weeks after switch (at week 7) safety monitoring bloods will be performed. 10 weeks after switch (week 13) follow-up cognitive testing and MR scan will be performed. Participants will remain on study drug for a further 2 weeks (until week 15) whilst completing follow-up sleep diary. At end of study patient will revert to original drug regimen or own physician's choice.

Intervention type

Drug

Phase

Phase IV

Drug names

Lopinavir, ritonavir, efavirenz

Primary outcome measures

A change in cognitive test scores at 10 weeks from switch; Timepoint(s): 10 weeks from switch to Kaletra

Secondary outcome measures

1.Change from baseline in resting-state and attentional processing task-based fMRI measured at 10 weeks from switch to Kaletra
2. Change from baseline of sleep quality measured at 10 weeks from switch to Kaletra
3. Change in cerebral metabolite profile (on magnetic resonance spectroscopy) measured at 10 weeks from switch to Kaletra

Overall trial start date

01/11/2012

Overall trial end date

31/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Documented HIV-1 viral load (VL) measurement =200 copies/ml within 4 months preceding study entry and no VL exceeding 200c/ml within 1 year prior to study entry. The constraint of >1 year of HIV infection is to remove any CNS effects of acute retroviral syndrome.
2. Documented HIV-1 RNA viral load (VL) measurement of <50 copies/ml within the 4 months preceding study entry and no VL exceeding 200c/ml within 1year prior to study entry. This constraint is to remove any CNS effects of active viral replication at baseline, and / or potential change in level of viral replication during the study period.
3. On HAART (at least 3 anti-retroviral drugs from at least 2 classes) for at least 12 months prior to study entry.
4. On Efavirenz (EFV, Sustiva) for at least 6 months prior to study entry. This constraint is to remove acute neuropsychiatric effects of EFV which are typically clinically apparent in the first 4-6 weeks of therapy.
5. Patient has provided written informed consent for participation in the study prior to any study specific procedures
6. Age 18 to 65 years inclusive
7. Male and female participants

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 30

Participant exclusion criteria

1. Use of Kaletra or any other HIV protease inhibitor within 6 months of study entry
2. Current self-reported (within last 3 months) recreational drug use
3. Current self-reported weekly alcohol consumption exceeding 35 units / week
4. Known contra-indication to MRI scanning
5. Known hypersensitivity to Kaletra, or to ritonavir in pharmacokinetic boosting doses (100 or 200mg ritonavir daily)
6. Currently (within 6 weeks of study entry) receiving interferon therapy for treatment of chronic viral hepatitis, or expected to commence such treatment with the next 4 months
7. Severe renal or hepatic impairment;
8. Pregnancy, or women planning to become pregnant within next 6 months;
9. Women breastfeeding
10. Use of other investigational study drugs within 30 days prior to study entry (defined as date of randomisation into study)
11. Previous participation in this study

Recruitment start date

01/01/2013

Recruitment end date

31/12/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Newcastle Clinical Research Facility
Leazes Wing Royal Victoria Infirmary Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom

Sponsor information

Organisation

Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)

Sponsor details

Leazes Wing
Royal Victoria Infirmary
Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.newcastle-hospitals.org.uk/

Funders

Funder type

Industry

Funder name

Abbott Laboratories Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes