HIV-1 Infected Adult Subjects With HIV-associated Neurocognitive Disorders Despite Effective Antiretroviral Therapy

NCT ID: NCT04266002

Last Updated: 2020-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-01
• Study Completion Date: 2016-07-26

Brief 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 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).

Conditions

HIV-1-infection; HIV Associated Neurocognitive Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HIV-1 infected adult associated neurocognitiv

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)

Group Type: OTHER

Validation of Charter score for the CNS diffusion of antiretroviral drugs

Intervention Type: OTHER

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.

Interventions

Validation of Charter score for the CNS diffusion of antiretroviral drugs

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Subject (male or female) with HIV-1 infection

2. Subject is ≥ 18 years of age

3. 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

4. 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

5. Patient is willing and able to understand and provide written informed consent prior to participation in this study

Exclusion Criteria

1. Subject with HIV-2 infection

2. Subject with plasma viral load (HIV-1 RNA)> 500 copies/ml in the past year

3. 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)

4. Subject unable, according to the investigator, to meet the study requirements, including patients unable to perform cognitive tests

5. Subject with acute intercurrent disease

6. Patient with positive serology for HCV or HBsAg positive

7. 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.

8. Subject with a brain MRI or CSF analysis results that suggest another pathology than HIV associated neurocognitive disorder

9. 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

10. Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents

11. Subject at which the initial lumbar punction can't be achieved

12. Subject ≥65 years at the inclusion date, age with high risk of atherosclerotic disease

13. 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

14. Subject under curatorship or guardianship

15. Subject at which the initial cerebral MRI can't be achieved

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Ambroise Paré Paris

OTHER

Sponsor Role: collaborator

Hôpital Franco-Britannique-Fondation Cognacq-Jay

OTHER

Sponsor Role: lead

Responsible Party

Gilles Force, MD

Study promotor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Philippe AEGERTER

Role: STUDY_DIRECTOR

Clinical Research Unit

Locations

Hôpital d'Argenteuil

Argenteuil, , France

Hôpital Intercommunal Robert Ballanger

Aulnay-sous-Bois, , France

Centre Hospitalier de Bligny

Briis-sous-Forges, , France

Hôpital Mignot Centre Hospitalier de Versailles

Chesnay, , France

Hôpital Raymond Poincaré

Garches, , France

Centre Hospitalier de Gonesse

Gonesse, , France

Institut Hospitalier Franco- Britannique

Levallois-Perret, , France

Centre Hospitalier Marc Jacquet

Melun, , France

Centre Hospitalier René Dubois

Pontoise, , France

Hôpital Delafontaine

Saint-Denis, , France

Centre Hospitalier Intercommunal de Poissy Germain en Laye

Saint-Germain-en-Laye, , France

Hôpital Foch

Suresnes, , France

Countries

France

Other Identifiers

IHFB001

Identifier Type: -

Identifier Source: org_study_id