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Clinical Trials

MainTitle

Integrase and Maraviroc Intensification in Neurocognitive Dysfunction (InMIND)

This study is currently recruiting participants. (see Contacts and Locations)

Verified September 2017 by National Institute of Allergy and Infectious Diseases (NIAID)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)


Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT02519777

First received: August 6, 2015
Last updated: September 13, 2017
Last Verified: September 2017
History of Changes
Purpose

Purpose

People infected with HIV often have cognitive dysfunction even if they are on antiretroviral therapy (ART) and have undetectable viral loads. The purpose of this study is to evaluate if the addition of maraviroc (MVC) and dolutegravir (DTG) (which are two antiretroviral [ARV] medications) to participants' existing ART regimens will improve participants' neurocognitive performance.

Condition Intervention Phase
HIV Infections

Drug : Placebo for maraviroc (MVC)
Drug : Placebo for dolutegravir (DTG)
Drug : Dolutegravir (DTG)
Drug : Maraviroc (MVC)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blinded, Placebo-Controlled Trial Comparing Antiretroviral Intensification With Maraviroc and Dolutegravir With No Intensification or Intensification With Dolutegravir Alone for the Treatment of Cognitive Impairment in HIV

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Change in normalized composite neurocognitive test score at Week 48 from pre-entry [ Time Frame: Measured at Week 48 ]
    The normalized neurocognitive test score is defined as the average of z-scores on the following tests: Neurocognitive Test Battery for CRSs in the United States: Attention/Working Memory (Symbol Search Trail Making A) Speed of Information Processing (Stroop Word, Stroop Color, Digit Symbol) Executive Function (Trail Making B, Stroop Color/Word, Letter and Category Fluency) Verbal Learning (HVLT-R) Verbal Memory (Delayed Recall - HVLT-R) Fine Motor Skills/Complex Perceptual (Grooved Pegboard Bilateral) Language/Premorbid Skills (WRAT-4 Reading or WAT for participants with Spanish as their primary language) See the protocol for information on the Neurocognitive Test Battery for CRSs outside the United States.
Secondary Outcome Measures:
  • Number of treatment-related adverse events (AEs) [ Time Frame: Measured through Week 96 ]
  • Change of normalized composite neurocognitive test score at Weeks 24, 72, and 96 [ Time Frame: Measured through Week 96 ]
  • Change in functional status scores based on the instrumental activities of daily living (IADLs) form at Weeks 24, 48, 72, and 96 [ Time Frame: Measured through Week 96 ]
  • Plasma HIV-1 RNA less than 50 copies/mL at Weeks 24, 48, and 96 [ Time Frame: Measured through Week 96 ]
  • CD4+ T-cell counts and changes from baseline to Weeks 24, 48, and 96 [ Time Frame: Measured through Week 96 ]
  • CD8+ T-cell counts and changes from baseline to Weeks 24, 48, and 96 [ Time Frame: Measured through Week 96 ]
  • Changes in residual viremia from baseline to Week 48 [ Time Frame: Measured through Week 48 ]
  • Changes in cell-associated HIV-1 RNA/DNA/2-long terminal repeat sequences (LTR) circles and single copy assay (SCA) from baseline to Week 48 [ Time Frame: Measured through Week 48 ]
  • Changes in T cell and monocyte activation from baseline to Week 48 [ Time Frame: Measured through Week 48 ]

Estimated Enrollment: 186
Study Start Date: March 2016
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Placebo Comparator: Arm A: Placebo MVC and placebo DTG
In addition to their existing ART regimens, participants in Arm A will receive placebo for MVC and placebo for DTG.
Drug: Placebo for maraviroc (MVC)

Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen

Drug: Placebo for dolutegravir (DTG)

Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen

Experimental: Arm B: DTG and placebo MVC
In addition to their existing ART regimens, participants in Arm B will receive DTG and placebo for MVC.
Drug: Placebo for maraviroc (MVC)

Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen

Drug: Dolutegravir (DTG)

Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen

Experimental: Arm C: MVC and DTG
In addition to their existing ART regimens, participants in Arm C will receive MVC and DTG
Drug: Dolutegravir (DTG)

Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen

Drug: Maraviroc (MVC)

Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen

Detailed Description:

HIV-infected people often have cognitive dysfunction (HIV-associated neurocognitive disorder, or HAND), which includes asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD), even if they are on ART and have undetectable viral loads. In this study, researchers will evaluate the effectiveness of adding MVC and DTG to the current ART regimen of HIV-infected people with undetectable (<50 copies/mL) plasma HIV-1 RNA who have mild to moderate neurocognitive impairment and who have been on stable ART for at least 6 months prior to study entry. The purpose of this study is to evaluate if the addition of MVC and DTG to participants' existing ART regimens will improve participants' neurocognitive performance.
Participants will be randomly assigned to one of three arms. All participants will remain on their existing ART regimens; they will take their assigned study drugs in addition to their ART regimen. Participants in Arm A will receive placebo for MVC and placebo for DTG. Participants in Arm B will receive DTG and placebo for MVC. Participants in Arm C will receive MVC and DTG. Study visits will occur at entry and Weeks 2, 4, 12, 24, 48, 72, and 96. Visits may include physical examinations, blood collection, neurocognitive testing, and questionnaires. Some participants may have an optional lumbar puncture procedure. Participants will have to return for refills of study drugs on Weeks 36, 60, and 84. No evaluations will be performed during these visits.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • HIV-1 infection, documented by:
    • a licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. NOTE: The term "licensed" refers to a United States Food and Drug Administration (FDA)-approved kit, which is required for all IND studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA. OR
    • Documentation of HIV diagnosis in the medical record by a healthcare provider.
  • On current ART for at least 6 months prior to study entry with no interruption in treatment of greater than or equal to 7 consecutive days. Note: The following ART changes are allowed:
    • Tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF)/TAF-containing fixed-dose combination regimens
    • Ritonavir (RTV) to cobicistat (COBI)/COBI-containing fixed-dose combination regimens
  • No plans to change ART while on study. Note: The following planned ART changes are allowed:
    • TDF to TAF/TAF-containing fixed-dose combination regimens
    • RTV to COBI/COBI-containing fixed-dose combination regimens
  • HIV-1 plasma RNA less than 50 copies/mL obtained within 90 days prior to study entry by any FDA-approved assay at any United States laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.
  • No more than one HIV-1 plasma RNA greater than or equal to 50 and less than 200 copies/mL (only one "blip") in the past 6 months with a subsequent HIV-1 plasma RNA less than 50 copies/mL. NOTE: There should be no plasma HIV-1 RNA greater than 200 copies/mL within the 6 months prior to study entry.
  • HAND diagnosis (ANI, MND, or HAD) within 60 days prior to study entry. HAND is defined as at least mild impairment on neurocognitive testing (more than one standard deviation below appropriate normative data in two domains of functioning) and no severely confounding factors.
  • Screening laboratory values obtained within 60 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs:
    • Absolute neutrophil count (ANC) greater than or equal to 500/mm^3
    • Hemoglobin greater than or equal to 7.5 g/dL
    • Platelet count greater than or equal to 40,000/mm^3
    • Creatinine less than or equal to 2.0 x upper limit of normal (ULN)
    • Aspartate transaminase (AST) less than or equal to 5 x ULN
    • Alanine transaminase (ALT) less than 3 x ULN
    • Alkaline phosphatase less than or equal to 5 x ULN
    • Total bilirubin less than 1.5 x ULN. NOTE: If the potential participant is taking an indinavir (IDV)- or atazanavir (ATV)-containing regimen at the time of screening, total bilirubin less than or equal to 5 x ULN is acceptable.
    • Creatinine clearance (CrCl) greater than or equal to 60 mL/min, either measured or estimated by Cockcroft-Gault equation. NOTE: A calculator for estimating the CrCl can be found at www.fstrf.org/ACTG/ccc.html
  • Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, ie, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, hysterectomy or bilateral salpingectomy or bilateral oophorectomy or tubal ligation) must have a negative serum or urine pregnancy test by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC) / CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs within 48 hours prior to study entry
  • Females of reproductive potential must agree not to participate in the conception process (ie, active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, must use at least one reliable form of contraception. Female participants must use contraceptives while receiving study treatment and for 6 weeks after stopping study treatment. More information on this criterion is available in the protocol.
  • Men and women 18 years of age and older who are able to complete the neuropsychological tests
  • Ability and willingness of participant or a legally authorized representative (see protocol for more information) to provide informed consent
  • Ability and willingness to take oral study medications


Exclusion Criteria:
  • Current or past medical condition(s) that in the opinion of the investigator prevents attribution of the cause of cognitive impairment to HIV. For example:
    • Major depressive disorder with psychotic features
    • Traumatic Brain Injury (TBI) with a clear impact on activities of daily living
    • Developmental delay, intellectual deficit, and/or severe educational disability resulting in some dependence for activities of daily living
    • Ongoing substance use disorder with significant impact on activities of daily living. Difficult or impossible to determine whether cognitive or functional decline is due to substance use or HIV, or both
    • Evidence of intoxication or withdrawal during the screening evaluation
    • Central nervous system (CNS) infections or opportunistic conditions: brain abscess (bacterial, mycobacterial, fungal or Toxoplasma), meningitis with persistent neurologic impairment, primary CNS lymphoma, progressive multifocal leukoencephalopathy (PML), or another structural brain lesion with neurological sequelae
    • Other CNS conditions: non-opportunistic primary or metastatic brain tumors, uncontrolled seizure disorder, progressive multiple sclerosis, stroke with neurological sequelae, or dementia due to causes other than HIV (eg, Alzheimer's disease)
    • Constitutional illness (eg, persistent unexplained fever, diarrhea, significant weight loss, disabling weakness) within 30 days of screening
    • Known untreated B12 deficiency or malnutrition (body mass index [BMI] less than 18) at screening
  • Evidence of current hepatitis C virus infection (HCV) (ie, HCV antibody [Ab] positive within 90 days prior to study entry unless also shown to be plasma HCV RNA negative within the same time period)
  • Unstable and advanced liver disease (as defined by the presence of at least one of the following: ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice)
  • Prior or current use of any CCR5 antagonist (such as MVC and cenicriviroc [CVC]) and integrase inhibitor (such as RAL, DTG, and elvitegravir [EVG])
  • Current use of any medication, including antiretrovirals, prohibited in the study (refer to the A5324 protocol-specific web page [PSWP] for the prohibited medications)
  • Breastfeeding
  • Presence of an AIDS-defining opportunistic infection within 6 months prior to entry. Note: Refer to the A5324 Manual of Operations (MOPS) for the list of AIDS-defining opportunistic infections.
  • Active syphilis or treatment for syphilis within 90 days prior to study entry. NOTE: Active syphilis is defined as four-fold increase in serum rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL) tests in an individual with past syphilis, or newly reactive serum RPR or VDRL with a reactive confirmatory test (enzyme immunoassays [EIA] or chemiluminescent assay [CIA], T. pallidum particle agglutination [TP-PA], or fluorescent treponemal antibody absorbed [FTA-ABS]).
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or
their formulation

contacts and locations

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02519777

Locations

United States, California
University of Southern California CRS Recruiting
Los Angeles, California, United States, 90033-1079
Contact: Luis M. Mendez    323-343-8283    lmendez@usc.edu
UCLA CARE Center CRS Recruiting
Los Angeles, California, United States, 90035
Contact: Arezou S. Akha, M.D., M.S.    310-557-3798    asadighi@mednet.ucla.edu
UCSD Antiviral Research Center CRS Recruiting
San Diego, California, United States, 92103
Contact: Jill Kunkel, R.N.    619-543-8080    jkunkel@ucsd.edu
Harbor-UCLA CRS Recruiting
Torrance, California, United States, 90502
Contact: Mario Guerrero    424-201-3000 ext 7318    mguerrero@labiomed.org
United States, Colorado
University of Colorado Hospital CRS Recruiting
Aurora, Colorado, United States, 80045
Contact: Mary Graham Ray, R.N., M.S.N.    303-724-0712    graham.ray@ucdenver.edu
United States, District of Columbia
Whitman-Walker Health CRS Recruiting
Washington, D.C., District of Columbia, United States, 20005
Contact: Anna Wimpelberg, B.A.    202-797-3589    AWimpelberg@whitman-walker.org
United States, Florida
The University of Miami AIDS Clinical Research Unit (ACRU) CRS Recruiting
Miami, Florida, United States, 33136
Contact: Hancy Brignol, B.S.N., M.H.S.A.    305-243-3838    hbrignol@med.miami.edu
United States, Georgia
The Ponce de Leon Center CRS Recruiting
Atlanta, Georgia, United States, 30308-2012
Contact: Ericka Patrick, M.S.N.    404-616-6313    erpatri@emory.edu
United States, Illinois
Northwestern University CRS Recruiting
Chicago, Illinois, United States, 60611
Contact: Baiba Berzins, M.P.H.    312-695-5012    Baiba@northwestern.edu
Rush University CRS Recruiting
Chicago, Illinois, United States, 60612
Contact: Antoinette Lewis    312-942-2050    antoinette_lewis@rush.edu
United States, Maryland
Johns Hopkins University CRS Recruiting
Baltimore, Maryland, United States, 21205
Contact: Ilene Wiggins, R.N.    410-614-2766    iwiggin1@jhmi.edu
United States, Massachusetts
Massachusetts General Hospital CRS (MGH CRS) Recruiting
Boston, Massachusetts, United States, 02114
Contact: Theresa Flynn, R.N., M.S.N., A.N.P., B.S.N.    617-724-0072    tflynn@partners.org
United States, Missouri
Washington University Therapeutics (WT) CRS Recruiting
Saint Louis, Missouri, United States, 63110-1010
Contact: Michael K. Klebert    314-747-1098    mklebert@dom.wustl.edu
United States, New Jersey
New Jersey Medical School Clinical Research Center CRS Recruiting
Newark, New Jersey, United States, 07103
Contact: Baljinder Singh    973-972-3811    singhba@njms.rutgers.edu
United States, New York
Weill Cornell Chelsea CRS Recruiting
New York, New York, United States, 10010
Contact: Todd Stroberg, R.N., B.S.N.    212-746-7198    tstrober@med.cornell.edu
Columbia P&S CRS Recruiting
New York, New York, United States, 10032-3732
Contact: Steven Palmer, P.A. -C    212-342-2958    sp500@cumc.columbia.edu
Weill Cornell Uptown CRS Recruiting
New York, New York, United States, 10065
Contact: Louise Walshe    212-746-7864    ljw2001@med.cornell.edu
University of Rochester Adult HIV Therapeutic Strategies Network CRS Recruiting
Rochester, New York, United States, 14642
Contact: Mary Adams    585-275-4768    Maryb_adams@urmc.rochester.edu
United States, North Carolina
Chapel Hill CRS Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Susan Pedersen    919-966-6713    spederse@med.unc.edu
Greensboro CRS Recruiting
Greensboro, North Carolina, United States, 27401
Contact: Kim Epperson, R.N., B.S.N., CRC    1-336-832-3262    kim.epperson@conehealth.com
United States, Ohio
Cincinnati Clinical Research Site Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Sharon Kohrs, R.N., B.S.N.    513-584-6383    kohrssd@ucmail.uc.edu
Case Clinical Research Site Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Baum, R.N.    216-844-2546    jb@clevelandactu.org
Ohio State University CRS Recruiting
Columbus, Ohio, United States, 43210
Contact: Kathy Watson, B.S.N.    614-293-5856    kathy.watson@osumc.edu
United States, Pennsylvania
Penn Therapeutics, CRS Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Eileen B. Donaghy, C.R.N.P.    215-349-8092    eileen.donaghy2@uphs.upenn.edu
University of Pittsburgh CRS Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Patricia Peters, R.Ph.    412-383-1434    pep1@pitt.edu
United States, Rhode Island
The Miriam Hospital Clinical Research Site (TMH CRS) CRS Recruiting
Providence, Rhode Island, United States, 02906
Contact: Pamela Poethke, R.N.    401-793-4971    ppoethke@lifespan.org
United States, Tennessee
Vanderbilt Therapeutics (VT) CRS Recruiting
Nashville, Tennessee, United States, 37204
Contact: Beverly O. Woodward, M.S.N., R.N.    615-936-8516    beverly.o.woodward@vanderbilt.edu
United States, Texas
Trinity Health and Wellness Center CRS Recruiting
Dallas, Texas, United States, 75208
Contact: Lauren Rogers, CCRC    972-807-7370    lauren.rogers@aidsarms.org
Houston AIDS Research Team CRS Recruiting
Houston, Texas, United States, 77030
Contact: Maria L. Martinez    713-500-6718    Maria.L.Martinez@uth.tmc.edu
United States, Washington
University of Washington AIDS CRS Recruiting
Seattle, Washington, United States, 98104-9929
Contact: Christine Jonsson    206-744-8886    cjonsson@u.washington.edu
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS Recruiting
San Juan, Puerto Rico, 00935
Contact: Sylvia I. Davila Nieves, M.Sc.    1-787-767-9192    sylvia.davila1@upr.edu

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: Kevin Robertson, PhD University of North Carolina
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT02519777   History of Changes  
Other Study ID Numbers: A5324  
  11909  
Study First Received: August 6, 2015  
Last Updated: September 13, 2017  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

HIV-Associated Neurocognitive Disorder

Additional relevant MeSH terms:
HIV Infections
Maraviroc
Dolutegravir

ClinicalTrials.gov processed this data on October 20, 2017
This information is provided by ClinicalTrials.gov.