A Phase IV, Open-label, Randomised, Pilot Clinical Trial Designed to Evaluate the Potential Neurotoxicity of Dolutegravir/Lamivudine/Abacavir in Neurosymptomatic HIV Patients and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide. DREAM Study (DREAM)

A phase IV, multicentre, randomised, open-label, pilot clinical trial designed to evaluate HIV-infected, aviremic patients who receive treatment with the combination of DTG/3TC/ABC and who have neuropsychiatric adverse effects that, in the opinion of the investigators, may be related to taking DTG/3TC/ABC, if they improve after switching antiretroviral therapy to the combination of ELV/COBI/FTC/TAF.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: DTG/3TC/ABC + ELV/COBI/FTC/TAF; Drug: ELV/COBI/FTC/TAF

Detailed Description

we estimate that 64 participants will need to be enrolled in the study to demonstrate symptomatic improvement after switching antiretroviral therapy from DTG/3TC/ABC to ELV/COBI/FTC/TAF.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain
    • Hospital Ramón y Cajal
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Fundación Jimenez Diaz
  • Madrid, Spain
    • Hospital Univ. Infanta Leonor
  • Madrid, Spain
    • Hospital Univ. La Princesa
  • Madrid
    • Majadahonda, Madrid, Spain
      • Hospital Puerta de Hierro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient > 18 years of age diagnosed with HIV using normal serology techniques.
• Current antiretroviral therapy with DTG/3TC/ABC.
• HIV viral load < 50 copies/mL for at least 12 weeks prior to signing the consent form [(]confirmed by two assays at least 12 weeks apart with viremia < 50 copies/mL between both). If the patient has a recent routine blood test available (≤ 4 weeks) that includes determining HIV viral load, these results may be used for the screening visit. If this test is not available, or the test is more than four weeks old, viral load will be determined on the day of screening in order to confirm that the patient meets this criterion.

• Appearance or worsening of the following symptoms compared to when DTG/3TC/ABC was started:

  • Symptoms of anxiety or depression
  • Insomnia or other sleep disturbances
  • Headache
  • Cognitive complaints (attention, concentration or memory)
  • Alterations in behaviour (irritability, aggressiveness or agitation)
  • Dizziness of neurological or neurologically-mediated origin

Exclusion Criteria:

• Determination of at least one HIV viral load ≥ 50 copies/mL in the last 12 weeks.
• Allergy, intolerance or existence of resistance mutations to any of the components of ELV/COBI/FTC/TAF
• History of active CNS infections
• Active psychosis, major depression with psychotic symptoms or autolytic ideation
• Dementia or mental retardation
• Drug use with a diagnosis of abuse or dependence according to DSM-5 criteria
• Illnesses that may interfere with the study procedures
• Claustrophobia
• Presence of magnetisable devices in the body
• Inability to complete any of the study procedures
• Pregnant or nursing women, as well as women of childbearing age who do not agree to use an adequate birth control method.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; Patients who postpone switching from DTG/3TC/ABC to ELV/COBI/FTC/TAF four weeks:	Drug: DTG/3TC/ABC + ELV/COBI/FTC/TAF; Patients continuing on treatment with DTG/3TC/ABC after the randomization for 4 weeks, and then switch to ELV/COBI/FTC/TAF for 24 weeks
Experimental: Arm 2; Patients who switch from DTG/3TC/ABC to ELV/COBI/FTC/TAF during the baseline visit	Drug: ELV/COBI/FTC/TAF; Treatment with ELV/COBI/FTC/TAF during 24 weeks since randomized.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare changes in the severity of neuropsychiatric symptoms potentially associated with the use of DTG/3TC/ABC, perceived by patients randomised to begin isolated symptomatic treatment or treatment associated with switching antiretroviral therapy.	To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the ACTG adverse effects scale. anxiety and depression scale.	Week 4
To compare changes in the severity of neuropsychiatric symptoms potentially associated with the use of DTG/3TC/ABC, perceived by patients randomised to begin isolated symptomatic treatment or treatment associated with switching antiretroviral therapy.	To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the pittsburgh sleep quality index.	Week 4
To compare changes in the severity of neuropsychiatric symptoms potentially associated with the use of DTG/3TC/ABC, perceived by patients randomised to begin isolated symptomatic treatment or treatment associated with switching antiretroviral therapy.	To compare, between the two arms of the study, changes in the percentage and in the severity of neuropsychiatric symptoms compiled using the depression scale.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate changes in the severity of neuropsychiatric symptoms potentially associated with the use of DTG/3TC/ABC after switching to ELV/COBI/FTC/TAF	To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the ACTG adverse effects scale.	Week 4
To evaluate changes in the severity of neuropsychiatric symptoms potentially associated with the use of DTG/3TC/ABC after switching to ELV/COBI/FTC/TAF	To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the pittsburgh sleep quality index	Week 4
To evaluate changes in the severity of neuropsychiatric symptoms potentially associated with the use of DTG/3TC/ABC after switching to ELV/COBI/FTC/TAF	To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the hospital anxiety and depression scale.	Week 4
To evaluate changes in neurocognitive function and volumetric, spectroscopic, tractographic and cerebral perfusion markers, acquired by Magnetic Resonance Imaging, after switching from DTG/3TC/ABC to ELV/COBI/FTC/TAF	To evaluate the change in global neurocognitive function (global deficit score) and cognitive domains (T-scores) in the volumes of the different structures of the brain using MRI volumetric techniques; the change in levels of neuronal integrity estimated by determining N-acetylaspartate levels in the structures of the frontal lobe and the basal ganglia using spectroscopy.	Week 24 after the switching
To evaluate changes in neurocognitive function and volumetric, spectroscopic, tractographic and cerebral perfusion markers, acquired by Magnetic Resonance Imaging, after switching from DTG/3TC/ABC to ELV/COBI/FTC/TAF	To evaluate the change in global neurocognitive function (global deficit score) and cognitive domains (T-scores) in the volumes of the different structures of the brain using MRI volumetric techniques; the change in the levels of white matter integrity estimated using the diffusion tensor imaging MRI technique.	Week 24 after the switching
To evaluate changes in neurocognitive function and volumetric, spectroscopic, tractographic and cerebral perfusion markers, acquired by Magnetic Resonance Imaging, after switching from DTG/3TC/ABC to ELV/COBI/FTC/TAF	To evaluate the change in global neurocognitive function (global deficit score) and cognitive domains (T-scores) in the volumes of the different structures of the brain using MRI volumetric techniques; the change in the levels of brain inflammation estimated by determining the levels of choline and myo-inositol in the structures of the frontal lobe and basal ganglia using spectroscopy.	Week 24 after the switching
Percentages of virologic failure	To evaluate the percentages of virologic failure after switching antiretroviral therapy from DTG/3TC/ABC to ELV/COBI/FTC/TAF	Week 24 after the switching

Collaborators and Investigators

• Sponsor: Fundacion SEIMC-GESIDA

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2017
• Primary Completion (Actual): April 23, 2019
• Study Completion (Actual): April 23, 2019

Study Registration Dates

• First Submitted: February 14, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Poisoning; HIV Infections; Neurotoxicity Syndromes
• Other Study ID Numbers: GESIDA 9016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No