- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02159027
Maraviroc and NeuroAIDS Pathogenesis
August 27, 2021 updated by: University of Hawaii
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
48
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
San Juan, Puerto Rico, 00936
- Puerto Rico Clinical and Translational Research Consortium
-
-
-
-
Hawaii
-
Honolulu, Hawaii, United States, 96813
- Clint Spencer Clinic, Hawaii Center for AIDS, University of Hawaii
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: placebo
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
|
Maraviroc placebo administered twice daily, dosage based on concomitant medication being taken.
|
Experimental: maraviroc
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
|
Maraviroc administered twice daily, dosage based on concomitant medication being taken.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
48 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in monocyte subsets and function
Time Frame: 48 weeks
|
Change in monocyte subsets based on CD14 and CD16 expression by flow cytometry; Change in inflammatory and neurotoxic mediators (sCD14, TNFalpha, sCD163 and neopterin
|
48 weeks
|
Change in HIV DNA content within MO subsets
Time Frame: 48 weeks
|
Change in HIV DNA content specifically within each MO subsets
|
48 weeks
|
Change in brain metabolites by magnetic resonance spectroscopy
Time Frame: 48 weeks
|
Change in neuronal and inflammatory brain metabolites globally within brain and in select brain regions
|
48 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Cecilia M. Shikuma, M.D., University of Hawaii
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2015
Primary Completion (Actual)
February 1, 2019
Study Completion (Actual)
February 1, 2019
Study Registration Dates
First Submitted
June 5, 2014
First Submitted That Met QC Criteria
June 6, 2014
First Posted (Estimate)
June 9, 2014
Study Record Updates
Last Update Posted (Actual)
August 30, 2021
Last Update Submitted That Met QC Criteria
August 27, 2021
Last Verified
August 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Neurocognitive Disorders
- HIV Infections
- Dementia
- AIDS Dementia Complex
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- HIV Fusion Inhibitors
- Viral Fusion Protein Inhibitors
- CCR5 Receptor Antagonists
- Maraviroc
Other Study ID Numbers
- H024
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on AIDS Dementia Complex
-
University Hospital, Basel, SwitzerlandTerminatedAIDS-related Dementia ComplexSwitzerland
-
National Institute of Mental Health (NIMH)TerminatedHIV Infections | Healthy | AIDS Dementia Complex | AIDS-Related Dementia Complex | HIV-Associated Cognitive Motor Complex | HIV-Dementia | AIDS EncephalopathyUnited States
-
Centre Hospitalier Universitaire Saint PierreFonds iris-Recherche, Fondation Roi Baudouin, BelgiumCompletedAIDS-Related Dementia ComplexBelgium
-
Johns Hopkins UniversityTerminatedHIV Dementia | HIV-Associated Cognitive Motor ComplexUnited States
-
University of PennsylvaniaNational Institute on Drug Abuse (NIDA)CompletedHIV Associated Cognitive Motor ComplexUnited States
-
National Institutes of Health Clinical Center (CC)CompletedDepression | HIV Infections | HIV-Associated Cognitive Motor ComplexUnited States
-
Holdsworth House Medical PracticeCompletedHIV-1-Associated Cognitive Motor Complex
-
National Institute of Mental Health (NIMH)TerminatedHIV-Associated Cognitive Motor ComplexUnited States
-
University of California, Los AngelesUnknown
-
Universidad Nacional Autonoma de MexicoRecruitingTelerehabilitation | Neuropsychology | HIV DementiaMexico
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States