NCT03163277

Brief Summary

Neurocognitive disorders are still highly prevalent in the HAART era; despite a dramatic reduction in dementia cases, 15-50% of patients may develop mild or asymptomatic neurocognitive disorders (HIV-associated neurocognitive disorders, HAND). Among other hypothesis neurotoxicity of antiretrovirals has been postulated but its impact is unknown. Our hypothesis is that using drugs with reduced in vitro neurotoxicity may improve cognition in HIV-positive patients withHAND. 76 patients with HAND will be randomized to either continue their treatment or switch to emtricitabine, darunavir/cobicistat, maraviroc. Patients will be re-tested 6 months later.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P25-P50 for phase_4 hiv

Timeline
Completed

Started May 2017

Typical duration for phase_4 hiv

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 15, 2017

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

May 19, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 23, 2017

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2020

Completed
Last Updated

November 6, 2020

Status Verified

November 1, 2020

Enrollment Period

3.1 years

First QC Date

May 19, 2017

Last Update Submit

November 5, 2020

Conditions

HivNeurocognitive Dysfunction

Outcome Measures

Primary Outcomes (1)

  • 6-month variation in global deficit score in NPZ-8 complete neurocognitive tests according to the study arm;

    Global deficit score

    6 months

Secondary Outcomes (7)

  • rs-fMRI

    6 months

  • EEG-LORETA

    6 months

  • CSF HIV RNA

    6 months

  • CSF markers

    6 months

  • Blood Brain Barrier Integrity

    6 months

  • +2 more secondary outcomes

Study Arms (2)

Standard of care

NO INTERVENTION

Continue current antiretroviral regimen

Reduced Neurotoxicity Arm

EXPERIMENTAL

Emtricitabine plus darunavir/cobicistat plus maraviroc

Drug: emtricitabine, darunavir/cobicistat, maraviroc

Interventions

emtricitabine, darunavir/cobicistat, maravirocDRUG

Treatment change

Reduced Neurotoxicity Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age above \>18 years;
  • Confirmed HIV-positivity;
  • Diagnosed with HAND according to the Frascati Criteria;
  • On combination antiretroviral treatment;
  • No evidence of major resistance associated mutations on previous plasma or CSF samples;
  • Plasma HIV RNA \<50 copies/mL;
  • CSF HIV RNA \<50 copies/mL;
  • R5-tropic virus as detected by a genotype or phenotype based test before starting HAART or genotype-based test performed on HIV DNA in the previous 12 months;

You may not qualify if:

  • the use of drugs having major drug-to-drug interaction with maraviroc (for instance rifampicin);
  • the use of efavirenz- or darunavir-containing regimens at baseline;
  • confounding comorbidities that may influence or affect the diagnosis of HAND including developmental disability, history of traumatic brain injury or of cerebrovascular accident;
  • a previous diagnosis of central nervous system opportunistic, autoimmune, neurodegenerative or neoplastic disease;
  • severe untreated depression;
  • active alcohol or recreational substance abuse (in the previous 3 months);
  • not fluent in Italian or unable to complete the neurocognitive tests.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Torino

Torino, Italy

Location

Related Publications (1)

  • Stroffolini G, Lazzaro A, Barco A, Pirriatore V, Vai D, Giaccone C, Nigra M, Atzori C, Trunfio M, Bonora S, Di Perri G G, Calcagno A. Changes in Cerebrospinal Fluid, Liver and Intima-media-thickness Biomarkers in Patients with HIV-associated Neurocognitive Disorders Randomized to a Less Neurotoxic Treatment Regimen. J Neuroimmune Pharmacol. 2023 Dec;18(4):551-562. doi: 10.1007/s11481-023-10086-7. Epub 2023 Oct 31.

    PMID: 37906406DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency SyndromeCognition Disorders

Interventions

EmtricitabineDarunavirCobicistatMaraviroc

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesSulfonamidesAmidesOrganic ChemicalsCarbamatesAcids, AcyclicCarboxylic AcidsSulfonesSulfur CompoundsFuransThiazolesAzolesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsTriazoles

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Full Professore of Infectious Diseases

Study Record Dates

First Submitted

May 19, 2017

First Posted

May 23, 2017

Study Start

May 15, 2017

Primary Completion

June 30, 2020

Study Completion

June 30, 2020

Last Updated

November 6, 2020

Record last verified: 2020-11

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)