Plain English Summary
Background and study aims
HIV is a virus that attacks the immune system, weakening the body's ability to fight infections and disease. HIV is treated with a combination of antiretroviral drugs which stops the virus replicating in the body and allows your immune system to recover. This prevents you from developing many illnesses related to the HIV virus. However, some people can still develop attention and memory problems known as cognitive function impairment. The aim of this study is to see if adding in a new antiretroviral drug has an effect on cognitive function.
Who can participate?
Patients aged 18 or over with HIV and clinically significant cognitive impairment.
What does the study involve?
The study is up to 16 weeks long and there are a total of 6 visits. For 8 weeks participants receive the new medication in addition to their current treatment. At the start and end of the study participants have a lumbar puncture (where a needle is inserted into the lower part of the spine) and an MRI scan and on three occasions complete a series of tests to assess their brain function. There are safety blood tests at all visits.
What are the possible benefits and risks of participating?
There is no direct benefit to the participants but the information gained from this study may be of benefit in the treatment of HIV-infected patients in the future. There are possible side effects of the treatment that include diarrhoea, vomiting, rash, headache and tiredness. There are also risks associated with having a lumbar puncture, including pain at the site and headaches.
Where is the study run from?
Imperial College Healthcare NHS Trust (UK)
When is the study starting and how long is it expected to run for?
October 2015 to September 2016
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Mr Kenneth Legg
Mr Kenneth Legg
Clinical Trials Centre
St Mary's Hospital
+44 (0)20 3312 1464
Dr Alan Winston
Clinical Trials Centre
Winston Churchill Wing
St. Mary’s Hospital
A feasibility study to assess the effects of AntiretroViral Intensification with Cenicriviroc for the management of HIV-associated Cognitive Impairment
To assess if the addition of Cenicriviroc to current antiretroviral treatment is acceptable, safe and tolerable for persons living with HIV, to measure the amount of cenicriviroc in the cerebrospinal fluid, and to find out whether it improves cognitive function in patients previously identified as having clinical cognitive dysfunction.
Brighton & Sussex REC South-East Coast, approved 24/11/2015, amendment 1 05/01/2016, amendment 2 25/01/2016, ethics ref: 15-LOC-1887
Phase II feasibility study
Primary study design
Secondary study design
Non randomised study
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
This is a phase II feasibility study to assess changes in patients who have been identified as having cognitive function impairment following the addition of a new drug to an existing effective regime of three HIV antiretroviral drugs.
This is an intensification study of patients stable on a triple combination of HIV antiretroviral therapy. Cenicriviroc at a dose of either 25 mg, 150 mg or 300 mg as oral tablets will be taken once daily (dose is dependent on the participants current treatment regime). The Cenicriviroc will be taken for 8 weeks and a safety visit will be performed 4 weeks after discontinuing the trial drug. This is a single arm study.
Primary outcome measures
1. Acceptability (measured via patient questionnaires) measured at week 8
2. Pharmacokinetic results (measured via CSF and plasma pharmacokinetics) measured at week 8
3. Cerebral function parameters (cognitive testing, neuro-imaging modalities) measured at week 8
Secondary outcome measures
Descriptive results of patient questionnaires and laboratory parameters measured at week 8
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Aged 18 or over at screening, male or female subjects
2. Documented HIV-infected
3. Undetectable plasma HIV RNA (<200 copies/mL) for at least 6 months
4. Demonstrated clinically significant cognitive impairment
5. On cART comprising of BHIVA guideline recommended therapies (2015 guidelines) with the exception of elvitegravir/cobicistat and rilpivirine
6. Comorbidities, if present, are stably managed for at least 6 months
7. No clinically significant recreational drug use or alcohol dependence
8. Male subjects who are heterosexually active must use two forms of barrier contraception (e.g., condom and diaphragm) during heterosexual intercourse, from screening through completion of the study
9. Female subjects may be eligible to enter and participate into the study if she:
9.1. Is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy
9.2. Is of child-bearing potential with a negative pregnancy test at both Screening and Day 0 and agrees to use one of the following methods of contraception to avoid pregnancy:
9.2.1. Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of study drug, throughout the study, and for at least 2 weeks after discontinuation of all study medications
9.2.2. Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
9.2.3. Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion)
9.2.4. Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject
9.2.5. Approved hormonal contraception
9.2.6. Any other method with published data showing that the expected failure rate is <1% per year
Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of study medication.
Target number of participants
Participant exclusion criteria
1. Current major depression (score of less than 15 on PHQ-9 score at study screening)
2. Chronic neurological diseases (e.g., epilepsy and stroke; at the discretion of the investigator)
3. History of severe head injury (with loss of consciousness for >30 minutes)
4. Cerebral AIDS defining infections
5. Current intravenous drug use (past six months)
6. Severe psychiatric disease (at the discretion of the investigator)
7. Contra-indication for MRI scan (e.g., claustrophobia, metal in body, physically unable to lie flat)
8. Contraindications to lumbar-puncture examination (at the discretion of the investigator)
9. Current or previous use of CCR5 inhibitors (maraviroc, cenicriviroc or others)
10. Disallowed medication which may interact with cenicriviroc
11. Chronic liver disease
12. Laboratory investigations at screening out with the follow cut-offs:
12.1. Haemoglobin < 8.5 g/dL
12.2. Absolute neutrophil count < 1000
12.3. Platelet count < 100,000
12.4. ALT or AST> 5 x upper limit of normal
12.5. Estimated creatinine clearance < 50 mL/min (Cockcroft and Gault 1979)
13. In the opinion of the investigator unable to comply with study procedures
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Imperial College Healthcare NHS Trust
Clinical Trials Centre Winston Churchill Wing St Mary's Hospital Praed Street
National Institute for Health Research
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Available on request
Results - basic reporting