Effect of Cenicriviroc on HIV Neurocognitive Impairment
Condition: AIDS Dementia Complex; HIV-1-Associated Cognitive Motor Complex; Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; AIDS Dementia Complex; Dementia; Immunologic Deficiency Syndromes
Intervention: cenicriviroc
Intervention description: 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
Intervention MeSH terms: Cenicriviroc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: AIDS Dementia Complex; HIV-1-Associated Cognitive Motor Complex; Human Immunodeficiency Virus

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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

          -  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