Back to resultsA 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)
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
ELV/COBI/FTC/TAF
DTG/3TC/ABC + ELV/COBI/FTC/TAF
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
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.
Sites / Locations
- Hospital Puerta de Hierro
- Hospital Fundación Jimenez Díaz
- Hospital Ramón y Cajal
- Hospital Univ. Infanta Leonor
- Hospital Univ. La Princesa
- Hospital Universitario La Paz
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm 1
Arm 2
Arm Description
Patients who postpone switching from DTG/3TC/ABC to ELV/COBI/FTC/TAF four weeks:
Patients who switch from DTG/3TC/ABC to ELV/COBI/FTC/TAF during the baseline visit
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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
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.
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.
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.
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.
Percentages of virologic failure
To evaluate the percentages of virologic failure after switching antiretroviral therapy from DTG/3TC/ABC to ELV/COBI/FTC/TAF
Full Information
NCT ID
NCT03067285
First Posted
February 14, 2017
Last Updated
February 3, 2020
Sponsor
Fundacion SEIMC-GESIDA
1. Study Identification
Unique Protocol Identification Number
NCT03067285
Brief 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
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
September 8, 2017 (Actual)
Primary Completion Date
April 23, 2019 (Actual)
Study Completion Date
April 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion SEIMC-GESIDA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A phase IV, open-label, randomised, pilot clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1
Arm Type
Active Comparator
Arm Description
Patients who postpone switching from DTG/3TC/ABC to ELV/COBI/FTC/TAF four weeks:
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
Patients who switch from DTG/3TC/ABC to ELV/COBI/FTC/TAF during the baseline visit
Intervention Type
Drug
Intervention Name(s)
ELV/COBI/FTC/TAF
Intervention Description
Treatment with ELV/COBI/FTC/TAF during 24 weeks since randomized.
Intervention Type
Drug
Intervention Name(s)
DTG/3TC/ABC + ELV/COBI/FTC/TAF
Intervention Description
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
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
Week 4
Title
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.
Description
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.
Time Frame
Week 4
Title
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.
Description
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.
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
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
Description
To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the ACTG adverse effects scale.
Time Frame
Week 4
Title
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
Description
To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the pittsburgh sleep quality index
Time Frame
Week 4
Title
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
Description
To evaluate the change in the percentage and in the severity of neuropsychiatric symptoms compiled using the hospital anxiety and depression scale.
Time Frame
Week 4
Title
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
Description
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.
Time Frame
Week 24 after the switching
Title
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
Description
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.
Time Frame
Week 24 after the switching
Title
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
Description
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.
Time Frame
Week 24 after the switching
Title
Percentages of virologic failure
Description
To evaluate the percentages of virologic failure after switching antiretroviral therapy from DTG/3TC/ABC to ELV/COBI/FTC/TAF
Time Frame
Week 24 after the switching
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
State/Province
Madrid
Country
Spain
Facility Name
Hospital Fundación Jimenez Díaz
City
Madrid
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Hospital Univ. Infanta Leonor
City
Madrid
Country
Spain
Facility Name
Hospital Univ. La Princesa
City
Madrid
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
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