Maraviroc and NeuroAIDS Pathogenesis

NCT02159027 | Completed Phase 2 DMC

• 1 other identifier: H024
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 2

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.

Conditions

AIDS Dementia Complex

Keywords

Human Immunodeficiency Virus; AIDS Dementia Complex

Outcome Measures

Primary Outcomes (1)

• Change in Neuropsychological Performance

  Change in global neuro-psychological Z scores and change in various neuro-psychological Z subdomains will be assessed

  48 weeks

Secondary Outcomes (3)

• Changes in monocyte subsets and function

  48 weeks

• Change in HIV DNA content within MO subsets

  48 weeks

• Change in brain metabolites by magnetic resonance spectroscopy

  48 weeks

Study Arms (2)

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

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

Drug: Maraviroc

Interventions

Maraviroc DRUG

Maraviroc administered twice daily, dosage based on concomitant medication being taken.

Also known as: Selzentry

maraviroc

Placebo DRUG

Maraviroc placebo administered twice daily, dosage based on concomitant medication being taken.

placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Hawaii: lead
• ViiV Healthcare: collaborator
• University of Puerto Rico: collaborator

Study Sites (2)

Clint Spencer Clinic, Hawaii Center for AIDS, University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Puerto Rico Clinical and Translational Research Consortium

San Juan, 00936, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 25227930 RESULT

MeSH Terms

Conditions

AIDS Dementia Complex; Acquired Immunodeficiency Syndrome

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurocognitive Disorders; Mental Disorders; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Cecilia M. Shikuma, M.D.

  University of Hawaii

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2014
• First Posted: June 9, 2014
• Study Start: June 1, 2015
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: August 30, 2021

Record last verified: 2021-08

Locations

US (1); PR (1)