AIDS Dementia ComplexPhase 2/3NCT02159027
Maraviroc and NeuroAIDS Pathogenesis
A Phase 2/3 study testing Maraviroc in people with AIDS Dementia Complex, run by University of Hawaii at 2 sites in 2 countries.
Trial summary
Maraviroc is an antiretroviral medication that may help in improving mental function in HIV infected patients with mental problems by decreasing inflammatory tendencies. We will test this in a clinical trial of 42 HIV infected individuals with some mild to moderate mental problems who are already on HIV medications… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- AIDS Dementia Complex
- What is being tested?
- Maraviroc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2015to Feb 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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
- Documentation of HIV-1 infection by an FDA approved test at any time prior to study entry.
- Receipt of ARV medication uninterrupted for > 1 year leading up to the screening period; brief interruptions for toxicity purposes will be evaluated on a case by case basis and may be allowed
- Screening plasma HIV RNA < 50 copies/ml within 3 months of entry
- Willingness for both 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 between 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
Who cannot join
- Currently receiving or having used a CCR5 antagonist as part of an antiretroviral regimen within 6 months of study entry
- Plasma HIV RNA > 100 copies/ml at any time within 6 months of study entry
- History of HIV-2
- Diagnosis of cirrhosis
- Active or inadequately treated tuberculosis (TB) infection, or inadequate treatment for a positive purified protein derivative (PPD) test. Adequate treatment is defined as meeting the current recommendations of the Centers of Disease Control and Prevention (CDC), National Institutes of Health (NIH) and the HIV Medicine Association of the Infectious Diseases Society of America (IDSA) guidelines33 or other CDC recommendations if the patient was treated before the current recommendations or before coinfection with HIV.
- Uncontrolled seizure disorder
Show all 26Show fewer
- Current malignancy or history of past malignancies excluding basal cell CA and Kaposi's sarcoma restricted to the skin, unless subject considered cured.
- Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.
- Requirement for acute therapy for any AIDS-defining illness or other serious medical illnesses (in the opinion of the site investigator) within 14 days prior to entry.
- Chronic illnesses including hematologic, pulmonary, and autoimmune diseases and endocrinopathies, except for stable controlled diabetes or cardiovascular disease in the view of the investigator and stable testosterone or thyroid medication use
- Known hypersensitivity to MVC or its excipients
- Anticipated need for specific prescription medications. Unwillingness to stop from eating grapefruit or using St. John's wort.
- Chronic use of over-the-counter (OTC) medications unless approved by Study Investigator
- Hemoglobin < 9.0; Absolute neutrophil count < 500/μL; Platelet count < 40,000/μL; AST (SGOT) and ALT (SGPT) > 5x ULN; Lipase > 2.0 x ULN
- Estimated creatinine clearance < 30 cc/min using Cockcroft and Gault method
- Abnormal EKG unless determined by the Investigator to be not clinically significant.
- Presence of any condition that would interfere with the absorption, distribution, metabolism, or excretion of the drug
- Current illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with the protocol requirements
- Pregnancy or breast-feeding, intent to become pregnant during the study
- 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
- Any factor that precludes MRI scan including presence of metal or exposure to metal work (e.g. metal grinder/worker) and claustrophobia
- Any CNS pathology which, in the judgment of the investigator, will interfere with the ability to assess study change in MRSI
- Learning disability, history of head injury with prolonged loss of consciousness or cognitive sequelae, history of opportunistic infection of the brain or other non-HIV etiologies that, in the judgment of the investigator, can explain the subjects's mild to moderate cognitive performance.
- Serum B12 or folate below the lower limits of normal
- Abnormal TSH, except when free T4 is within normal limits
- History of untreated or inadequately treated positive RPR
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Clint Spencer Clinic, Hawaii Center for AIDS, University of Hawaii
Honolulu, Hawaii, 96813
Puerto Rico1 site
Puerto Rico Clinical and Translational Research Consortium
San Juan, 00936
About this study
Maraviroc is an antiretroviral medication that may help in improving mental function in HIV infected patients with mental problems by decreasing inflammatory tendencies. We will test this in a clinical trial of 42 HIV infected individuals with some mild to moderate mental problems who are already on HIV medications and doing well. We will add Maraviroc or a sugar pill to their HIV medications and see if mental function improves over 48 weeks. This study will be conducted at 2 sites in Hawaii and Puerto Rico.
Read the detailed description
We hypothesize that maraviroc (MVC) will lead to improved cognition as assessed by improvement in neuropsychological (NP) performance. We hypothesize that MVC therapy leads to (1) decrease in HIV infection of monocytes (MO), particularly of CD16-expressing MO and (2) phenotypic and functional secretory changes suggestive of decrease in MO immune activation, and that these changes will lead to less HIV infected activated MO trafficking to the CNS, less CNS inflammation and neuronal damage, and ultimately improved cognition. We will test this in a 48 week trial in 42 HIV infected individuals on suppressive antiretroviral therapy (ART) with mild to moderate cognitive dysfunction. These individuals will be randomized to intensify their ART in double-blind fashion to MVC vs placebo. The primary endpoint will be change in NPZglobal. Magnetic resonance spectroscopy (MRS)/magnetic resonance spectroscopic imaging (MRSI) will be conducted to assess potential alterations in inflammatory and neuronal brain chemicals.
- Conditions
- AIDS Dementia Complex
- Being tested
- Maraviroc, Placebo
- Keywords
- Human Immunodeficiency Virus, AIDS Dementia Complex
- 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.
MaravirocDrug
Also called Selzentry
Maraviroc administered twice daily, dosage based on concomitant medication being taken.
PlaceboDrug
Maraviroc placebo administered twice daily, dosage based on concomitant medication being taken.
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | placebo identical in appearance to maraviroc 150 and 300 mg tablets will be added to each subjects antiretroviral regimen at doses as recommended by the package insert Receives: Drug: Placebo |
| maraviroc | Experimental | Maraviroc Tablets are available as 150 mg and 300 mg tablets. Each subject will add maraviroc to their current antiretroviral regimen with dosage based on recommendations as per maraviroc package insert Receives: Drug: Maraviroc |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Neuropsychological Performance
Change in global neuro-psychological Z scores and change in various neuro-psychological Z subdomains will be assessed
Measured: 48 weeks
Secondary outcomes (3)
Changes in monocyte subsets and function
Change in monocyte subsets based on CD14 and CD16 expression by flow cytometry; Change in inflammatory and neurotoxic mediators (sCD14, TNFalpha, sCD163 and neopterin
Measured: 48 weeks
Change in HIV DNA content within MO subsets
Change in HIV DNA content specifically within each MO subsets
Measured: 48 weeks
Change in brain metabolites by magnetic resonance spectroscopy
Change in neuronal and inflammatory brain metabolites globally within brain and in select brain regions
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 posted9 Jun 2014 (estimated)
- Study startJun 2015
- Primary completionFeb 2019
- Study completionFeb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Hawaii
- Sponsor type
- University, hospital or other
- Collaborators
- ViiV Healthcare, University of Puerto Rico
- Responsible party
- Sponsor
- Investigators
- Cecilia M. Shikuma, M.D., Principal investigator, University of Hawaii
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02159027
- Sponsor's protocol ID
- H024
- Status last verified
- Aug 2021
- First submitted
- 5 Jun 2014
- Last updated
- 30 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ndhlovu LC, Umaki T, Chew GM, Chow DC, Agsalda M, Kallianpur KJ, Paul R, Zhang G, Ho E, Hanks N, Nakamoto B, Shiramizu BT, Shikuma CM. Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND). J Neurovirol. 2014 Dec;20(6):571-82. doi: 10.1007/s13365-014-0279-x. Epub 2014 Sep 17.
PubMed 25227930
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maraviroc and NeuroAIDS Pathogenesis
- ClinicalTrials.gov ID
- NCT02159027
- Acronym / sponsor ID
- H024
- Conditions
- AIDS Dementia Complex
- Keywords
- Human Immunodeficiency Virus, AIDS Dementia Complex
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of HawaiiUniversity, hospital or other
- Collaborators
- ViiV Healthcare, University of Puerto Rico
- Study start
- Jun 2015 (actual)
- Primary completion
- Feb 2019 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 9 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Maraviroc is an antiretroviral medication that may help in improving mental function in HIV infected patients with mental problems by decreasing inflammatory tendencies. We will test this in a clinical trial of 42 HIV infected individuals with some mild to moderate mental problems who are already on HIV medications and doing well. We will add Maraviroc or a sugar pill to their HIV medications and see if mental function improves over 48 weeks. This study will be conducted at 2 sites in Hawaii and Puerto Rico.
Detailed description
We hypothesize that maraviroc (MVC) will lead to improved cognition as assessed by improvement in neuropsychological (NP) performance. We hypothesize that MVC therapy leads to (1) decrease in HIV infection of monocytes (MO), particularly of CD16-expressing MO and (2) phenotypic and functional secretory changes suggestive of decrease in MO immune activation, and that these changes will lead to less HIV infected activated MO trafficking to the CNS, less CNS inflammation and neuronal damage, and ultimately improved cognition. We will test this in a 48 week trial in 42 HIV infected individuals on suppressive antiretroviral therapy (ART) with mild to moderate cognitive dysfunction. These individuals will be randomized to intensify their ART in double-blind fashion to MVC vs placebo. The primary endpoint will be change in NPZglobal. Magnetic resonance spectroscopy (MRS)/magnetic resonance spectroscopic imaging (MRSI) will be conducted to assess potential alterations in inflammatory and neuronal brain chemicals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: Placeboplacebo identical in appearance to maraviroc 150 and 300 mg tablets will be added to each subjects antiretroviral regimen at doses as recommended by the package insert |
| maraviroc | Experimental | Drug: MaravirocMaraviroc Tablets are available as 150 mg and 300 mg tablets. Each subject will add maraviroc to their current antiretroviral regimen with dosage based on recommendations as per maraviroc package insert |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Documentation of HIV-1 infection by an FDA approved test at any time prior to study entry.
- Receipt of ARV medication uninterrupted for > 1 year leading up to the screening period; brief interruptions for toxicity purposes will be evaluated on a case by case basis and may be allowed
- Screening plasma HIV RNA < 50 copies/ml within 3 months of entry
- Willingness for both 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 between 18 to 70 years.
Key exclusion criteria (26 listed)
- Currently receiving or having used a CCR5 antagonist as part of an antiretroviral regimen within 6 months of study entry
- Plasma HIV RNA > 100 copies/ml at any time within 6 months of study entry
- History of HIV-2
- Diagnosis of cirrhosis
- Active or inadequately treated tuberculosis (TB) infection, or inadequate treatment for a positive purified protein derivative (PPD) test. Adequate treatment is defined as meeting the current recommendations of the Centers of Disease Control and Prevention (CDC), National Institutes of Health (NIH) and the HIV Medicine Association of the Infectious Diseases Society of America (IDSA) guidelines33 or other CDC recommendations if the patient was treated before the current recommendations or before coinfection with HIV.
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 |
|---|---|---|
| MaravirocAlso: SelzentryMaraviroc administered twice daily, dosage based on concomitant medication being taken. | Drug | maraviroc |
| PlaceboMaraviroc placebo administered twice daily, dosage based on concomitant medication being taken. | Drug | placebo |
Primary outcome
Change in Neuropsychological Performance
Time frame: 48 weeks
Change in global neuro-psychological Z scores and change in various neuro-psychological Z subdomains will be assessed
3 secondary outcomes
Changes in monocyte subsets and function
Time frame: 48 weeks
Change in HIV DNA content within MO subsets
Time frame: 48 weeks
Change in brain metabolites by magnetic resonance spectroscopy
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2021.
- Results publication: PubMed 25227930Ndhlovu LC, Umaki T, Chew GM, Chow DC, Agsalda M, Kallianpur KJ, Paul R, Zhang G, Ho E, Hanks N, Nakamoto B, Shiramizu BT, Shikuma CM. Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND). J Neurovirol. 2014 Dec;20(6):571-82. doi: 10.1007/s13365-014-0279-x. Epub 2014 Sep 17.
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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 M. Shikuma, M.D. principal investigator
University of Hawaii
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Maraviroc in people with AIDS Dementia Complex, run by University of Hawaii at 2 sites in 2 countries.
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 26 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 30 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Puerto Rico. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 in Neuropsychological Performance (time frame: 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 NCT02159027, 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 30 Aug 2021.