HIVPhase 4CogUKNCT01367236
Changes in Cerebral Function in Treatment Naive HIV-1 Infected Subjects Commencing Either Boosted Atazanavir With Truvada or Boosted Darunavir With Maraviroc and Kivexa
A Phase 4 study testing novel treatment in people with HIV and Impaired Cognition, run by Imperial College London at 6 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, Impaired Cognition
- What is being tested?
- novel treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 6 sitesUnited Kingdom
- Study dates
- Jan 2013to Oct 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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*
Who cannot join
- • 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)
Show all 15Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United Kingdom6 sites
Birmingham Heartlands Hospital:
Birmingham
Brighton and Sussex University Hospital NHS Trust:
Brighton, BN1 9RE
Kings College Hospital
London, SE5 9RJ
Chelsea and Westminster Hospital NHS Trust
London, SW10 9NH
St. Mary's Hospital
London, W2 1NY
St. Thomas' Hospital
London
About this study
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.
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.
Read the 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.
- Conditions
- HIV, Impaired Cognition
- Being tested
- standard care, novel treatment
- Keywords
- HIV
- Medical subject headings
- Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
standard careDrug
- atazanavir 300 mg daily
- ritonavir 100 mg daily
- tenofovir 245 mg daily*
- emtricitabine 200 mg daily*
novel treatmentDrug
- darunavir 800 mg daily
- ritonavir 100 mg daily
- lamivudine 300 mg daily and abacavir 600mgs daily
- maraviroc 150 mg once daily
| Study group | Role | What they receive |
|---|---|---|
| standard care | Active comparator | treatment with:
* atazanavir 300 mg daily
* ritonavir 100 mg daily
* tenofovir 245 mg daily*
* emtricitabine 200 mg daily* * as the fixed dose combination Truvada™ Receives: Drug: standard care |
| Novel therapeutic approach | Active comparator | * 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 ™ Receives: Drug: novel treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Function, Global Cognitive Score (Z-score)
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.
Score increase means improved performance of cognitive function
Measured: 24 weeks, 48 weeks
Secondary outcomes (1)
Brain Function, Absolute Change Over 48 Weeks of N-acetyl Aspartate/Creatinine Ratio
The study team will assess the brain functions at each visit. The results of the MRI scans will be compared, changes in N-acetyl aspartate/creatinine ratio over 48 weeks.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2011 (estimated)
- Study startJan 2013
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Alan Winston, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01367236
- Sponsor's protocol ID
- 1733
- Other IDs
- 2011-002656-14
- Acronym
- CogUK
- Status last verified
- Oct 2019
- First submitted
- 3 Jun 2011
- Last updated
- 21 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mora-Peris B, Bouliotis G, Ranjababu K, Clarke A, Post FA, Nelson M, Burgess L, Tiraboschi J, Khoo S, Taylor S, Ashby D, Winston A. Changes in cerebral function parameters with maraviroc-intensified antiretroviral therapy in treatment naive HIV-positive individuals. AIDS. 2018 May 15;32(8):1007-1015. doi: 10.1097/QAD.0000000000001786.
PubMed 29438199
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01367236
- Acronym / sponsor ID
- CogUK / 1733
- Conditions
- HIV, Impaired Cognition
- Keywords
- HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Jan 2013 (actual)
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 7 Jun 2011 (estimated)
- Results
- Posted 21 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard care | Active comparator | Drug: standard caretreatment with: * atazanavir 300 mg daily * ritonavir 100 mg daily * tenofovir 245 mg daily* * emtricitabine 200 mg daily* * as the fixed dose combination Truvada™ |
| Novel therapeutic approach | Active comparator | Drug: novel treatment* 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 ™ |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- • existing neurological disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| standard care* atazanavir 300 mg daily * ritonavir 100 mg daily * tenofovir 245 mg daily* * emtricitabine 200 mg daily* | Drug | standard care |
| novel treatment* darunavir 800 mg daily * ritonavir 100 mg daily * lamivudine 300 mg daily and abacavir 600mgs daily * maraviroc 150 mg once daily | Drug | Novel therapeutic approach |
Primary outcome
Cognitive Function, Global Cognitive Score (Z-score)
Time frame: 24 weeks, 48 weeks
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. Score increase means improved performance of cognitive function
1 secondary outcome
Brain Function, Absolute Change Over 48 Weeks of N-acetyl Aspartate/Creatinine Ratio
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29438199Mora-Peris B, Bouliotis G, Ranjababu K, Clarke A, Post FA, Nelson M, Burgess L, Tiraboschi J, Khoo S, Taylor S, Ashby D, Winston A. Changes in cerebral function parameters with maraviroc-intensified antiretroviral therapy in treatment naive HIV-positive individuals. AIDS. 2018 May 15;32(8):1007-1015. doi: 10.1097/QAD.0000000000001786.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan Winston principal investigator
Imperial College London
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing novel treatment in people with HIV and Impaired Cognition, run by Imperial College London at 6 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Function, Global Cognitive Score (Z-score) (time frame: 24 weeks, 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01367236, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2019.