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

HIV Infections Clinical Trial

— DREAM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03067285
• Other study ID #: GESIDA 9016
• Status: Completed
• Phase: Phase 4
• Start date: September 8, 2017
• Est. completion date: April 23, 2019

Study information

• Verified date: August 2018
• Source: Fundacion SEIMC-GESIDA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: April 23, 2019
• Est. primary completion date: April 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections
• Neurotoxicity Syndromes

Intervention

Drug:
• ELV/COBI/FTC/TAF
Treatment with ELV/COBI/FTC/TAF during 24 weeks since randomized.
• 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

Locations

Country	Name	City	State
Spain	Hospital Fundación Jimenez Díaz	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Univ. Infanta Leonor	Madrid
Spain	Hospital Univ. La Princesa	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion SEIMC-GESIDA

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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