ClinicalTrials.gov
ClinicalTrials.gov Menu

Maraviroc and NeuroAIDS Pathogenesis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02159027
Recruitment Status : Recruiting
First Posted : June 9, 2014
Last Update Posted : January 26, 2018
Sponsor:
Collaborators:
ViiV Healthcare
University of Puerto Rico
Information provided by (Responsible Party):
University of Hawaii

Brief 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 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.

Condition or disease Intervention/treatment Phase
AIDS Dementia Complex Drug: Maraviroc Drug: Placebo Phase 2 Phase 3

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  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Maraviroc and NeuroAIDS Pathogenesis
Study Start Date : May 2015
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dementia HIV/AIDS
Drug Information available for: Maraviroc

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
Drug: Placebo
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
Drug: Maraviroc
Maraviroc administered twice daily, dosage based on concomitant medication being taken.
Other Name: Selzentry




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. Change in HIV DNA content within MO subsets [ Time Frame: 48 weeks ]
    Change in HIV DNA content specifically within each MO subsets

  3. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02159027


Contacts
Contact: Cecilia M Shikuma, M.D. 808 692-1328 shikuma@hawaii.edu
Contact: Dominic Chow, M.D. Ph.D. 808 692-1330 dominicc@hawaii.edu

Locations
United States, Hawaii
Clint Spencer Clinic, Hawaii Center for AIDS, University of Hawaii Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Debra Ogata-Arakaki, R.N.    808-692-1332    ogataara@hawaii.edu   
Contact: Nancy Hanks, R.N.    808-692-1336    nhanks@hawaii.edu   
Principal Investigator: Cecilia M. Shikuma, M.D.         
Sub-Investigator: Dominic Chow, M.D. Ph.D.         
Puerto Rico
Puerto Rico Clinical and Translational Research Consortium Recruiting
San Juan, Puerto Rico, 00936
Contact: Valerie E Wojna, MD    7877586250    valerie.wojna1@upr.edu   
Contact: Miriam Matos, MD    7877590306 ext 221    miriam.matos@upr.edu   
Sponsors and Collaborators
University of Hawaii
ViiV Healthcare
University of Puerto Rico
Investigators
Principal Investigator: Cecilia M. Shikuma, M.D. University of Hawaii

Publications of Results:
Responsible Party: University of Hawaii
ClinicalTrials.gov Identifier: NCT02159027     History of Changes
Other Study ID Numbers: H024
First Posted: June 9, 2014    Key Record Dates
Last Update Posted: January 26, 2018
Last Verified: January 2018

Keywords provided by University of Hawaii:
Human Immunodeficiency Virus
AIDS Dementia Complex

Additional relevant MeSH terms:
Dementia
AIDS Dementia Complex
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Maraviroc
CCR5 Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents