AIDS Dementia ComplexPhase 2NCT02128828
Effect of Cenicriviroc on HIV Neurocognitive Impairment
A Phase 2 study testing cenicriviroc in people with AIDS Dementia Complex and HIV-1-Associated Cognitive Motor Complex, run by University of Hawaii at 1 site in United States.
Trial summary
The study hypothesis is that cenicriviroc will improve cognition in HIV infected individuals with cognitive impairment. The investigators will study the effect of cenicriviroc on cognition in 24 subjects over a 24 week period. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- AIDS Dementia Complex, HIV-1-Associated Cognitive Motor Complex, Human Immunodeficiency Virus
- What is being tested?
- cenicriviroc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Jun 2016
- Phase
- Phase 2
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 4.2.1.1 Documentation of HIV-1 infection by an FDA approved test at any time prior to study entry
- On ARV medication uninterrupted for > 1 year leading up to the screening period
- Screening plasma HIV RNA < 50 copies/ml within 3 months of entry
- Willingness for males and females of childbearing potential to utilize 2 effective contraception methods (2 separate forms, one of which must be an effective barrier method), be non-heterosexually active or have a an exclusive vasectomized partner from screening throughout the duration of the study treatment and for 30 days following the last dose of study drugs.
- Age 18 to 70 years
- Ability and willingness to provide written informed consent
- Mild to moderate cognitive impairment with global neuropsychological (NP) test (NPZglobal) score of < -0.5 or a neurocognitive abnormality (<-0.5) in at least one cognitive domain known to be typically affected by HIV OR unimpaired
- On antiretroviral (ARV) therapy consisting of nucleoside reverse transcriptase inhibitors, atazanavir with/or without ritonavir, darunavir plus ritonavir, dolutegravir, raltegravir or efavirenz.
Who cannot join
- Receiving or used a CCR5 antagonist within 6 months of study entry
- Plasma HIV RNA > 100 copies/ml within 6 mo. of screening
- HIV-2
- Chronic hepatitis B (positive hepatitis B surface antigen)
- Chronic hepatitis C (positive hepatitis C antibody), except with proof of viral clearance and normal liver function tests
- Active or chronic liver disease
Show all 27Show fewer
- Active or inadequately treated tuberculosis infection, or inadequate treatment for a positive purified protein derivative test. Adequate treatment meets current recommendations of the Center for Disease Control, NIH and the HIV Medicine Association of the Infectious Diseases Society of America (IDSA) guidelines or other Center for Disease Control recommendations if patient was treated before the current recommendations or before coinfection with HIV.
- Prior/current diagnosis with other intracellular pathogens (Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans).
- Uncontrolled seizures
- Current or past malignancies excluding basal cell cancer and Kaposi's sarcoma (skin).
- Immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of entry.
- Requirement for acute therapy for AIDS-defining or other serious medical illnesses within 14 days of entry.
- Other chronic illnesses including hematologic, pulmonary, autoimmune diseases and endocrinopathies, except for stable controlled diabetes or cardiovascular disease in the view of the investigator and stable testosterone or thyroid therapy.
- Known hypersensitivity to CVC or its excipients
- Anticipated need for prescription medication not allowed in the study. Unwilling to stop eating grapefruit or using St. John's wort).
- Chronic use of over the counter medications unless approved by Study Investigator
- Hemoglobin < 8.5; Absolute neutrophil count < 1000; Platelet count < 100,000; serum glutamate oxaloacetate and pyruvate transaminase > 2.5x upper limit of normal ; Lipase > 2.0 x upper limit of normal
- Estimated creatinine clearance < 30 mL/min(Cockcroft and Gault 1979)
- Bradycardia, sinus rhythm <50 beats/min (bpm).
- Presence of any condition that would interfere with the absorption, distribution, metabolism, or excretion of the drug
- Current active illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with protocol requirements
- Pregnancy or breast-feeding
- History of moderate (Child-Pugh class B) or severe (Child-Pugh C) hepatic impairment
- Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable
- For MRI substudy [impaired]: Any factor that precludes MRI scan including presence of metal or exposure to metal work (e.g. metal grinder/worker) and claustrophobia
- For MRI substudy [impaired]: Any central nervous system pathology which, in the judgment of the investigator, will interfere with the ability to assess study change in magnetic resonance spectroscopy
- 4.2.2.28 For lumbar puncture substudy: Thrombocytopenia or other bleeding disorders (including ongoing anticoagulant therapy), suspected increased intracranial pressure or spinal epidural abscess, or any other factor which would increase risk of complications following lumbar puncture
Trial locations and contacts
1 site in 1 country.
About this study
Official title: H020: Single-Arm Open Label, Pilot Study of CCR5/CCR2 Inhibitor Cenicriviroc (CVC) for HIV Associated Neurocognitive Disorder (HAND)
The study hypothesis is that cenicriviroc will improve cognition in HIV infected individuals with cognitive impairment. The investigators will study the effect of cenicriviroc on cognition in 24 subjects over a 24 week period.
Read the detailed description
HIV-associated neurocognitive disease (HAND), particularly in its milder form, is estimated to occur in greater than 30% of HIV infected individuals in the era of potent antiretroviral therapy. As even mild disease leads to functional consequences with decreased ability to live independently, HAND is of substantial public health concern. HIV-induced immune activation/inflammation of monocytes (MO) may be primarily responsible for the development of HAND.
Cenicriviroc is a combined CCR5 and CCR2 chemokine co-receptor antagonist. The investigators hypothesize that dual CCR5 and CCR2 blockade with the use of CVC will lead to measurable reductions in MO activation and lead to cognitive improvement by decreasing HIV infection of MO and by interrupting the trafficking of such MO into the central nervous system.
The investigators propose a single arm, 24-week trial of CVC in 24 subjects with HIV-1 infection suppressed on ART (plasma HIV RNA < 50 copies/ml) for 1 year or more with mild to moderate cognitive impairment.
- Conditions
- AIDS Dementia Complex, HIV-1-Associated Cognitive Motor Complex, Human Immunodeficiency Virus
- Being tested
- cenicriviroc
- Keywords
- AIDS Dementia Complex, HIV-1-Associated Cognitive Motor Complex, Human Immunodeficiency Virus
- Medical subject headings
- AIDS Dementia Complex, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cenicrivirocDrug
Also called TBR-652
cenicriviroc given once daily for 24 weeks; number of pills dependent on recommended modifications based on patient's other antiretroviral medications and certain other medications anticipated to interact with cenicriviroc
| Study group | Role | What they receive |
|---|---|---|
| cenicriviroc | Experimental | cenicriviroc 50 mg tablets, number of tablets adjusted for other antiretroviral medications or other drugs, given once daily Receives: Drug: cenicriviroc |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 24 in Global Neuropsychological Performance
Raw scores from individual performance on 14 validated neuropsychological tests meant to assess various cognitive domains were converted into standardized z-scores adjusted for age, sex, and education. Z-scores from all tests were aggregated and averaged to determine each subject's Global Neuropsychological Performance Score; NPZ-Global). Z-scores follow a normal distribution with scores < '0' identifying poorer cognition than 'average' and scores > "0" identifying better cognition than average with -1 and +1 represented 1 SD below or higher than average.
Measured: baseline, week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2014 (estimated)
- Study startApr 2014
- Primary completionJun 2016
- Study completionJun 2016
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.
- Other trials for AIDS Dementia ComplexStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Hawaii
- Sponsor type
- University, hospital or other
- Collaborators
- Tobira Therapeutics, Inc.
- Responsible party
- Principal investigator, Cecilia Shikuma, University of Hawaii
- Investigators
- Cecilia Shikuma, MD, Principal investigator, University of Hawaii - Hawaii Center for AIDS (HICFA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02128828
- Sponsor's protocol ID
- H020
- Status last verified
- Aug 2020
- First submitted
- 4 Sep 2013
- Last updated
- 20 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- H020: Single-Arm Open Label, Pilot Study of CCR5/CCR2 Inhibitor Cenicriviroc (CVC) for HIV Associated Neurocognitive Disorder (HAND)
- ClinicalTrials.gov ID
- NCT02128828
- Acronym / sponsor ID
- H020
- Conditions
- AIDS Dementia Complex, HIV-1-Associated Cognitive Motor Complex, Human Immunodeficiency Virus
- Keywords
- AIDS Dementia Complex, HIV-1-Associated Cognitive Motor Complex, Human Immunodeficiency Virus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of HawaiiUniversity, hospital or other
- Collaborators
- Tobira Therapeutics, Inc.
- Study start
- Apr 2014
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 1 May 2014 (estimated)
- Results
- Posted 20 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study hypothesis is that cenicriviroc will improve cognition in HIV infected individuals with cognitive impairment. The investigators will study the effect of cenicriviroc on cognition in 24 subjects over a 24 week period.
Detailed description
HIV-associated neurocognitive disease (HAND), particularly in its milder form, is estimated to occur in greater than 30% of HIV infected individuals in the era of potent antiretroviral therapy. As even mild disease leads to functional consequences with decreased ability to live independently, HAND is of substantial public health concern. HIV-induced immune activation/inflammation of monocytes (MO) may be primarily responsible for the development of HAND.
Cenicriviroc is a combined CCR5 and CCR2 chemokine co-receptor antagonist. The investigators hypothesize that dual CCR5 and CCR2 blockade with the use of CVC will lead to measurable reductions in MO activation and lead to cognitive improvement by decreasing HIV infection of MO and by interrupting the trafficking of such MO into the central nervous system.
The investigators propose a single arm, 24-week trial of CVC in 24 subjects with HIV-1 infection suppressed on ART (plasma HIV RNA < 50 copies/ml) for 1 year or more with mild to moderate cognitive impairment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cenicriviroc | Experimental | Drug: cenicriviroccenicriviroc 50 mg tablets, number of tablets adjusted for other antiretroviral medications or other drugs, given once daily |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 4.2.1.1 Documentation of HIV-1 infection by an FDA approved test at any time prior to study entry
- On ARV medication uninterrupted for > 1 year leading up to the screening period
- Screening plasma HIV RNA < 50 copies/ml within 3 months of entry
- Willingness for males and females of childbearing potential to utilize 2 effective contraception methods (2 separate forms, one of which must be an effective barrier method), be non-heterosexually active or have a an exclusive vasectomized partner from screening throughout the duration of the study treatment and for 30 days following the last dose of study drugs.
- Age 18 to 70 years
Key exclusion criteria (27 listed)
- Receiving or used a CCR5 antagonist within 6 months of study entry
- Plasma HIV RNA > 100 copies/ml within 6 mo. of screening
- HIV-2
- Chronic hepatitis B (positive hepatitis B surface antigen)
- Chronic hepatitis C (positive hepatitis C antibody), except with proof of viral clearance and normal liver function tests
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 |
|---|---|---|
| cenicrivirocAlso: TBR-652cenicriviroc given once daily for 24 weeks; number of pills dependent on recommended modifications based on patient's other antiretroviral medications and certain other medications anticipated to interact with cenicriviroc | Drug | cenicriviroc |
Primary outcome
Change From Baseline to Week 24 in Global Neuropsychological Performance
Time frame: baseline, week 24
Raw scores from individual performance on 14 validated neuropsychological tests meant to assess various cognitive domains were converted into standardized z-scores adjusted for age, sex, and education. Z-scores from all tests were aggregated and averaged to determine each subject's Global Neuropsychological Performance Score; NPZ-Global). Z-scores follow a normal distribution with scores < '0' identifying poorer cognition than 'average' and scores > "0" identifying better cognition than average with -1 and +1 represented 1 SD below or higher than average.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Cecilia Shikuma, MD principal investigator
University of Hawaii - Hawaii Center for AIDS (HICFA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cenicriviroc in people with AIDS Dementia Complex and HIV-1-Associated Cognitive Motor Complex, run by University of Hawaii at 1 site in United States.
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 8 inclusion and 27 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 20 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 20 Aug 2020). 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?
Change From Baseline to Week 24 in Global Neuropsychological Performance (time frame: baseline, week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Aug 2020.