HIV-1-infectionNCT04266002
HIV-1 Infected Adult Subjects With HIV-associated Neurocognitive Disorders Despite Effective Antiretroviral Therapy
A study testing Validation of Charter score for the CNS diffusion of antiretroviral drugs in people with HIV-1-infection and HIV Associated Neurocognitive Disorder, run by Hôpital Franco-Britannique-Fondation Cognacq-Jay at 12 sites in France.
Trial summary
Prospective study in HIV-1 infected adult subjects with HIV-associated neurocognitive disorders despite effective antiretroviral therapy in plasma for more than one year, analyzing the evolution of cognitive disorders and markers of macrophagic inflammation in blood and cerebrospinal fluid, after a change in HIV… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV-1-infection, HIV Associated Neurocognitive Disorder
- What is being tested?
- Validation of Charter score for the CNS diffusion of antiretroviral drugs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 12 sitesFrance
- Study dates
- 1 Nov 2011to 26 Jul 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject (male or female) with HIV-1 infection
- Subject is ≥ 18 years of age
- Subject with a plasma viral load (HIV-1 RNA) undetectable for at least one year or with minimal replication <500 copies/ml for at least one year at the inclusion date
- Patient with HIV-associated neurocognitive disorders : at least two ability domains, documented by performance of at least 1.0 standard deviation below the mean for age-education appropriate norms on standardized neuropsychological tests
- Patient is willing and able to understand and provide written informed consent prior to participation in this study
Who cannot join
- Subject with HIV-2 infection
- Subject with plasma viral load (HIV-1 RNA)> 500 copies/ml in the past year
- Subject with acquired impairment in cognitive functioning involving only one ability domain, or involving at least two ability domains but with performance better than 1.0 standard deviation below the mean (no evidence of potential cognitive impairment)
- Subject unable, according to the investigator, to meet the study requirements, including patients unable to perform cognitive tests
- Subject with acute intercurrent disease
- Patient with positive serology for HCV or HBsAg positive
Show all 16Show fewer
- Subject with cognitive impairment related to another cause than HIV: other CNS infection, CNS neoplasm, cerebrovascular disease, preexisting neurologic disease or metabolic disorders, severe substance abuse, or systemic disease.
- Subject with a brain MRI or CSF analysis results that suggest another pathology than HIV associated neurocognitive disorder
- Subject requires treatment with immunomodulating agents (or may require such treatment during the two years monitoring) such as systemic corticosteroïds, interferons, interleukins, growth factor GM- CSF, or other targeted therapy that may interfere with macrophage markers of the study
- Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents
- Subject at which the initial lumbar punction can't be achieved
- Subject ≥65 years at the inclusion date, age with high risk of atherosclerotic disease
- Subject with significant depression : with a score ≥29 (or score
- ≥20 without questions 15 to 21) at Beck Depression Inventory II (1996 version), the neuropsychologist doesn't conduct the battery of cognitive tests
- Subject under curatorship or guardianship
- Subject at which the initial cerebral MRI can't be achieved
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
France12 sites
Hôpital d'Argenteuil
Argenteuil, 95100
Hôpital Intercommunal Robert Ballanger
Aulnay-sous-Bois, 93602
Centre Hospitalier de Bligny
Briis-sous-Forges, 91640
Hôpital Mignot Centre Hospitalier de Versailles
Chesnay, 78150
Hôpital Raymond Poincaré
Garches, 92380
Centre Hospitalier de Gonesse
Gonesse, 95500
Institut Hospitalier Franco- Britannique
Levallois-Perret, 92300
Centre Hospitalier Marc Jacquet
Melun, 77000
Centre Hospitalier René Dubois
Pontoise, 95300
Hôpital Delafontaine
Saint-Denis, 93200
Centre Hospitalier Intercommunal de Poissy Germain en Laye
Saint-Germain-en-Laye, 78100
Hôpital Foch
Suresnes, 92150
About this study
Official title: Prospective Study in HIV-1 Infected Adult Subjects With HIV-associated Neurocognitive Disorders Despite Effective Antiretroviral Therapy in Plasma, After a Change in HIV Treatment With an Increased of CHARTER Score ≥ 3 (Total Score ≥ 9)
Prospective study in HIV-1 infected adult subjects with HIV-associated neurocognitive disorders despite effective antiretroviral therapy in plasma for more than one year, analyzing the evolution of cognitive disorders and markers of macrophagic inflammation in blood and cerebrospinal fluid, after a change in HIV treatment with an increased of the new scale CHARTER score ≥ 3 (total treatment score to be ≥ 9)
Read the detailed description
Neurocognitive disorders are measured using Frascati 3-stage classification and Global Deficit Score, after the following 10 standardized battery test: Grooved Pegboard for dominant and non-dominant hand, Grefex Verbal Fluency, California Verbal Learning Test (CVLT), Digit Span Wechsler Adult Intelligence Scale III, modified Paced Auditory Serial Addition Test (60 items), WAIS III Digit Symbol Test, Trail Making Test A\&B, recall of CVLT and Wisconsin Card Sorting Test; and after the Beck Depression Inventory II (BDI), Inventory of Activity Daily Living part II (IADL) and 10-items Cognitive Complaint Questionnaire (CCQ). The global CNS Penetration Effectiveness (CPE) score of ARV treatment are the sum of the scores of each ARV the patient received, according to the last published scoring. For each drug class, we considered treatment intensification only for drugs with CPE score reaching at least 3 (no intensification if switch in same drug class with same CPE score). CPE score was corrected by drugs resistance status, using cumulative genotype interpreted with the 2012 ANRS algorithm (www.hivfrenchresistance.org; v.2012) at inclusion (CPE=0 if resistance).
- Being tested
- Validation of Charter score for the CNS diffusion of antiretroviral drugs
- Keywords
- CNS Penetration Effectiveness, Global Deficit Score, Cytokines, CSF Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Validation of Charter score for the CNS diffusion of antiretroviral drugsOther
IHFB001 (Neuroplustrois) is a pilot study, phase IV, open-label, multicenter in Ile-de-France region, trying to demonstrate the improvement of cognitive change after treatment characterized by its better diffusion in the central nervous system. The characteristics of the change in treatment are (Cn - Ci) ≥ 3 and Cn ≥ 9, where Cn is the Charter score of the new treatment and Ci the Charter score of the initial treatment.
| Study group | Role | What they receive |
|---|---|---|
| HIV-1 infected adult associated neurocognitiv | Other | HIV-1 infected adult subjects with HIV-associated neurocognitive disorders despite effective antiretroviral therapy in plasma for more than one year, analyzing the evolution of cognitive disorders with Global Deficit Score and HAND classification, and markers of macrophagic inflammation in blood and cerebrospinal fluid, after a change in HIV treatment with an increased of the new scale CHARTER score ≥ 3 (total treatment score to be ≥ 9) Receives: Other: Validation of Charter score for the CNS diffusion of antiretroviral drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
HIV associated neurocognitive disorders classification with Frascati 3-stage
Measured: Change from Baseline to Week 96
Secondary outcomes (65)
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
HIV associated neurocognitive disorders classification with Frascati 3-stage
Measured: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification. Global Deficit Score (from 0 with no deficit to 5 with high neurocognitive disorder) is calculated with the results of 10 standardized battery tests.
Measured: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification. Global Deficit Score (from 0 with no deficit to 5 with high neurocognitive disorder) is calculated with the results of 10 standardized battery tests.
Measured: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with changes in CD4 and CD8 cells in plasma cells, and plasma HIV-1 viral loads
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CD4 and CD8 cells are measured in plasma with flow cytometry (results in cells/µL).
Measured: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with changes in CD4 and CD8 cells in plasma cells, and plasma HIV-1 viral loads
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CD4 and CD8 cells are measured in plasma with flow cytometry (results in cells/µL).
Measured: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Plasma HIV-1 viral load will be measured with an ultra-sensitive technique with a threshold of 5 copies/mL.
Measured: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Plasma HIV-1 viral load will be measured with an ultra-sensitive technique with a threshold of 5 copies/mL.
Measured: Change from Baseline to Week 96
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score.Detectable viral load in CSF is defined as a result >5 copies/mL with ultrasensitive HIV-RNA measure.
Measured: Day 0
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score.Detectable viral load in CSF is defined as a result >5 copies/mL with ultrasensitive HIV-RNA measure.
Measured: Week 48
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score.Detectable viral load in CSF is defined as a result >5 copies/mL with ultrasensitive HIV-RNA measure.
Measured: Week 96
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results >100 copies/mL within one month. Virologic failure in the CSF is defined as a result >100 copies/mL
Measured: Week 12
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results >100 copies/mL within one month. Virologic failure in the CSF is defined as a result >100 copies/mL
Measured: Week 24
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results >100 copies/mL within one month. Virologic failure in the CSF is defined as a result >100 copies/mL
Measured: Week 36
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results >100 copies/mL within one month. Virologic failure in the CSF is defined as a result >100 copies/mL
Measured: Week 48
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results >100 copies/mL within one month. Virologic failure in the CSF is defined as a result >100 copies/mL
Measured: Week 60
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results >100 copies/mL within one month. Virologic failure in the CSF is defined as a result >100 copies/mL
Measured: Week 72
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results >100 copies/mL within one month. Virologic failure in the CSF is defined as a result >100 copies/mL
Measured: Week 84
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results >100 copies/mL within one month. Virologic failure in the CSF is defined as a result >100 copies/mL
Measured: Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in CSF: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CSF biomarkers were obtained using high-performance liquid chromatography coupled with fluorimetric detection for neopterin (nmol/L), using the Quanterix® single molecule array platform for neurofilament light protein (NF-L)(pg/mL), chemokine (C-C-motif) ligand-2 (CCL2)(pg/mL), interleukine 6 (IL6)(pg/mL), interleukine 8 (IL8)(pg/mL), chemokine (C-X-C-motif) ligand-10 (CXCL10)(pg/mL), and using an enzyme-linked immunosorbent assay (Biotechne®) for soluble CD14 (sCD14)(µg/mL) levels.
Measured: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in CSF: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CSF biomarkers were obtained using high-performance liquid chromatography coupled with fluorimetric detection for neopterin (nmol/L), using the Quanterix® single molecule array platform for neurofilament light protein (NF-L)(pg/mL), chemokine (C-C-motif) ligand-2 (CCL2)(pg/mL), interleukine 6 (IL6)(pg/mL), interleukine 8 (IL8)(pg/mL), chemokine (C-X-C-motif) ligand-10 (CXCL10)(pg/mL), and using an enzyme-linked immunosorbent assay (Biotechne®) for soluble CD14 (sCD14)(µg/mL) levels.
Measured: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in plasma: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Plasma biomarkers were obtained using high-performance liquid chromatography coupled with fluorimetric detection for neopterin (nmol/L), using the Quanterix® single molecule array platform for neurofilament light protein (NF-L)(pg/mL), chemokine (C-C-motif) ligand-2 (CCL2)(pg/mL), interleukine 6 (IL6)(pg/mL), interleukine 8 (IL8)(pg/mL), chemokine (C-X-C-motif) ligand-10 (CXCL10)(pg/mL), and using an enzyme-linked immunosorbent assay (Biotechne®) for soluble CD14 (sCD14)(µg/mL) levels.
Measured: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in plasma: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Plasma biomarkers were obtained using high-performance liquid chromatography coupled with fluorimetric detection for neopterin (nmol/L), using the Quanterix® single molecule array platform for neurofilament light protein (NF-L)(pg/mL), chemokine (C-C-motif) ligand-2 (CCL2)(pg/mL), interleukine 6 (IL6)(pg/mL), interleukine 8 (IL8)(pg/mL), chemokine (C-X-C-motif) ligand-10 (CXCL10)(pg/mL), and using an enzyme-linked immunosorbent assay (Biotechne®) for soluble CD14 (sCD14)(µg/mL) levels.
Measured: Change from Baseline to Week 96
To evaluate HIV associated neurocognitive disorders and Brain MRI change
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Brain MRI is performed before and after ARV change
Measured: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Brain MRI change
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Brain MRI is performed before and after ARV change
Measured: Change from Baseline to Week 96
To compare sensitivity and specificity of the 2 screening tests (FAB test and Modified - HIV Dementia Scale) for the diagnosis of HAND
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Altered Frontal Assessment Battery test is defined with a score ≤15/18 and altered modified-HIV Dementia Scale screening test is defined with a score ≤10/12.
Measured: Day 0
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Measured: Change from Baseline to Week 12
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Measured: Change from Baseline to Week 24
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Measured: Change from Baseline to Week 36
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Measured: Change from Baseline to Week 48
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Measured: Change from Baseline to Week 60
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Measured: Change from Baseline to Week 72
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Measured: Change from Baseline to Week 84
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Measured: Change from Baseline to Week 96
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Measured: Change from Baseline to Week 12
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Measured: Change from Baseline to Week 24
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Measured: Change from Baseline to Week 36
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Measured: Change from Baseline to Week 48
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Measured: Change from Baseline to Week 60
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Measured: Change from Baseline to Week 72
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Measured: Change from Baseline to Week 84
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Measured: Change from Baseline to Week 96
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Measured: Change from Baseline to Week 12
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Measured: Change from Baseline to Week 24
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Measured: Change from Baseline to Week 36
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Measured: Change from Baseline to Week 48
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Measured: Change from Baseline to Week 60
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Measured: Change from Baseline to Week 72
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Measured: Change from Baseline to Week 84
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Measured: Change from Baseline to Week 96
To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CPE changes are analysed with most recent genotypic algorithm (v.2016)
Measured: Change from Baseline to Week 48
To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CPE changes are analysed with most recent genotypic algorithm (v.2016)
Measured: Change from Baseline to Week 96
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Measured: Week 12
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Measured: Week 24
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Measured: Week 36
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Measured: Week 48
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Measured: Week 60
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Measured: Week 72
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Measured: Week 84
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Measured: Week 96
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Measured: Day 0
To study the trough levels of antiretroviral drugs in blood after ARV change
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Measured: Week 4
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Measured: Week 48
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Measured: Week 96
To study the cardiovascular risk evolution
Cardiovascular risk is measured with Framingham score, Systematic Coronary Risk Estimation, and D:A:D study model score
Measured: Change from Baseline to Week 48
To study the cardiovascular risk evolution
Cardiovascular risk is measured with Framingham score, Systematic Coronary Risk Estimation, and D:A:D study model score are calcul
Measured: Change from Baseline to Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2020
- Study start1 Nov 2011
- Primary completion29 Jun 2012
- Study completion26 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective Pilot study, open-label, multicenter in the Ile-de-France
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hôpital Franco-Britannique-Fondation Cognacq-Jay
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Ambroise Paré Paris
- Responsible party
- Principal investigator, Gilles Force, MD, Hôpital Franco-Britannique-Fondation Cognacq-Jay
- Investigators
- Philippe AEGERTER, Study director, Clinical Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04266002
- Sponsor's protocol ID
- IHFB001
- Status last verified
- Feb 2020
- First submitted
- 24 Jan 2020
- Last updated
- 12 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study in HIV-1 Infected Adult Subjects With HIV-associated Neurocognitive Disorders Despite Effective Antiretroviral Therapy in Plasma, After a Change in HIV Treatment With an Increased of CHARTER Score ≥ 3 (Total Score ≥ 9)
- ClinicalTrials.gov ID
- NCT04266002
- Acronym / sponsor ID
- IHFB001
- Keywords
- CNS Penetration Effectiveness, Global Deficit Score, Cytokines, CSF Inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Hôpital Franco-Britannique-Fondation Cognacq-JayUniversity, hospital or other
- Collaborators
- Hospital Ambroise Paré Paris
- Study start
- 1 Nov 2011 (actual)
- Primary completion
- 29 Jun 2012 (actual)
- Study completion
- 26 Jul 2016 (actual)
- First posted
- 12 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective study in HIV-1 infected adult subjects with HIV-associated neurocognitive disorders despite effective antiretroviral therapy in plasma for more than one year, analyzing the evolution of cognitive disorders and markers of macrophagic inflammation in blood and cerebrospinal fluid, after a change in HIV treatment with an increased of the new scale CHARTER score ≥ 3 (total treatment score to be ≥ 9)
Detailed description
Neurocognitive disorders are measured using Frascati 3-stage classification and Global Deficit Score, after the following 10 standardized battery test: Grooved Pegboard for dominant and non-dominant hand, Grefex Verbal Fluency, California Verbal Learning Test (CVLT), Digit Span Wechsler Adult Intelligence Scale III, modified Paced Auditory Serial Addition Test (60 items), WAIS III Digit Symbol Test, Trail Making Test A\&B, recall of CVLT and Wisconsin Card Sorting Test; and after the Beck Depression Inventory II (BDI), Inventory of Activity Daily Living part II (IADL) and 10-items Cognitive Complaint Questionnaire (CCQ). The global CNS Penetration Effectiveness (CPE) score of ARV treatment are the sum of the scores of each ARV the patient received, according to the last published scoring. For each drug class, we considered treatment intensification only for drugs with CPE score reaching at least 3 (no intensification if switch in same drug class with same CPE score). CPE score was corrected by drugs resistance status, using cumulative genotype interpreted with the 2012 ANRS algorithm (www.hivfrenchresistance.org; v.2012) at inclusion (CPE=0 if resistance).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective Pilot study, open-label, multicenter in the Ile-de-France
| Arm | Type | Receives |
|---|---|---|
| HIV-1 infected adult associated neurocognitiv | Other | Other: Validation of Charter score for the CNS diffusion of antiretroviral drugsHIV-1 infected adult subjects with HIV-associated neurocognitive disorders despite effective antiretroviral therapy in plasma for more than one year, analyzing the evolution of cognitive disorders with Global Deficit Score and HAND classification, and markers of macrophagic inflammation in blood and cerebrospinal fluid, after a change in HIV treatment with an increased of the new scale CHARTER score ≥ 3 (total treatment score to be ≥ 9) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject (male or female) with HIV-1 infection
- Subject is ≥ 18 years of age
- Subject with a plasma viral load (HIV-1 RNA) undetectable for at least one year or with minimal replication <500 copies/ml for at least one year at the inclusion date
- Patient with HIV-associated neurocognitive disorders : at least two ability domains, documented by performance of at least 1.0 standard deviation below the mean for age-education appropriate norms on standardized neuropsychological tests
- Patient is willing and able to understand and provide written informed consent prior to participation in this study
Key exclusion criteria (16 listed)
- Subject with HIV-2 infection
- Subject with plasma viral load (HIV-1 RNA)> 500 copies/ml in the past year
- Subject with acquired impairment in cognitive functioning involving only one ability domain, or involving at least two ability domains but with performance better than 1.0 standard deviation below the mean (no evidence of potential cognitive impairment)
- Subject unable, according to the investigator, to meet the study requirements, including patients unable to perform cognitive tests
- Subject with acute intercurrent disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Validation of Charter score for the CNS diffusion of antiretroviral drugsIHFB001 (Neuroplustrois) is a pilot study, phase IV, open-label, multicenter in Ile-de-France region, trying to demonstrate the improvement of cognitive change after treatment characterized by its better diffusion in the central nervous system. The characteristics of the change in treatment are (Cn - Ci) ≥ 3 and Cn ≥ 9, where Cn is the Charter score of the new treatment and Ci the Charter score of the initial treatment. | Other | HIV-1 infected adult associated neurocognitiv |
Primary outcome
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
Time frame: Change from Baseline to Week 96
HIV associated neurocognitive disorders classification with Frascati 3-stage
65 secondary outcomes
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
Time frame: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
Time frame: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
Time frame: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with changes in CD4 and CD8 cells in plasma cells, and plasma HIV-1 viral loads
Time frame: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with changes in CD4 and CD8 cells in plasma cells, and plasma HIV-1 viral loads
Time frame: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
Time frame: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
Time frame: Change from Baseline to Week 96
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
Time frame: Day 0
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
Time frame: Week 48
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
Time frame: Week 96
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Time frame: Week 12
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Time frame: Week 24
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Time frame: Week 36
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Time frame: Week 48
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Time frame: Week 60
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Time frame: Week 72
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Time frame: Week 84
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Time frame: Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in CSF: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
Time frame: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in CSF: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
Time frame: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in plasma: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
Time frame: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in plasma: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
Time frame: Change from Baseline to Week 96
To evaluate HIV associated neurocognitive disorders and Brain MRI change
Time frame: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Brain MRI change
Time frame: Change from Baseline to Week 96
To compare sensitivity and specificity of the 2 screening tests (FAB test and Modified - HIV Dementia Scale) for the diagnosis of HAND
Time frame: Day 0
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 12
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 24
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 36
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 48
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 60
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 72
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 84
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 96
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 12
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 24
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 36
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 48
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 60
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 72
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Time frame: Change from Baseline to Week 84
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe AEGERTER study director
Clinical Research Unit
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Validation of Charter score for the CNS diffusion of antiretroviral drugs in people with HIV-1-infection and HIV Associated Neurocognitive Disorder, run by Hôpital Franco-Britannique-Fondation Cognacq-Jay at 12 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9. (time frame: Change from Baseline to Week 96). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2020.