Clinical trial NCT03732625: Neuropsyquiatric Evolution After Introduction of Raltegravir QD in Substitution of Dolutegravir: NEAR QD Study
Official title: Neuropsyquiatric Evolution After Introduction of Raltegravir QD in Substitution of Dolutegravir: NEAR QD Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: HIV Infections
Keywords: HIV infection
neuropsychological adverse effects
Raltegravir
Lead sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-11-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multicenter, open, non-randomized pilot trial.
Primary purpose: OTHER

Brief summary: Open, multicenter, non randomized, single arm, pilot trial.

Detailed description: Open, multicenter, non randomized, single arm, pilot trial. The study is aimed at patients infected with HIV in triple antiretroviral therapy based on Dolutegravir (DTG) who experience neuropsychological adverse effects related to the treatment. After signing the informed consent, DTG will be replaced by Raltegravir (RAL) 1200 QD, maintaining the other two drugs that constituted the triple therapy established before the inclusion of the patient in the study.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Infection with chronic HIV-1.
* On triple therapy antiretroviral therapy based on abacavir/lamivudine (ABC/3TC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or tenofovir alafenamide/emtricitabine (TAF/FTC), whose third component is DTG in a dose of 50 mg / day.
* Presence of neuropsychiatric symptoms (insomnia, sleep disturbances, reduced concentration, dizziness, headaches, depression, restlessness or nervousness) with an intensity ≥ 2 on the DAIDS scale.
* Written informed consent to participate in the study.

Exclusion criteria:

* Pregnant women, nursing or of childbearing age who want to get pregnant.
* Concomitant use of any medication with potential risk of interaction with the therapy under study.
* Intolerance, hypersensitivity or previous resistance to the therapy under study or presence of any contraindication of it.
* Subjects in therapy with immunosuppressants or chemotherapy with cytotoxics, including interferon and interleukin-2 at the time of their inclusion in the study.
* Abuse of alcohol or any other substance that may interfere with adherence to treatment.
* Subjects who are participating in any other clinical study with the exception of those in which the treatment under study has been suspended for more than 12 weeks.
* AIDS event at the time of diagnosis of HIV infection or in the 3 months prior to its inclusion
* Any other clinical condition or previous treatment that makes the subject unsuitable for the study or that compromises their ability to comply with the treatment dosing requirements.
* History of mental illness or diagnosis of neuropsychological symptoms prior to the use of DTG.
* Presence of genotypic mutations that confer resistance to ABC, TDF / TAF, 3TC or FTC.
* Chronic liver disease in the cirrhosis phase (either by ultrasound criteria or fibroscan ≥ 14.5 KPa)
* Consumption of tobacco ≥ 20 cigarettes / day.

Additional Exclusion Criteria (for patients recruited at the Costa del Sol Hospital in Marbella only):

* History or diagnosis of claustrophobia, or inability to lie flat on the back inside the positron emission tomograph or MRI chamber for a period of 20 minutes.
* Contraindication to perform an MRI, including the presence of a cardiac pacemaker or other electronic device or ferromagnetic metallic foreign bodies in vulnerable positions evaluated by a standard questionnaire prior to MRI.

Primary outcomes:
measure: Evaluate improvement in neuropsychiatric symptoms at 12 weeks (Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events)
timeFrame: 12 weeks
Secondary outcomes:
measure: Neuropsychiatric symptoms
timeFrame: 24 weeks
measure: Interruptions of the medication for any reason
timeFrame: 24 weeks
measure: Change in quality of life (WHOQoL-bref questionnaire)
timeFrame: 24 weeks
measure: Variation of the result in the Hospital, Anxiety and Depression (HAD) scale
timeFrame: 24 weeks
measure: Variation of the result on the Pittsburgh Sleep Quality Index (PSQI) scale
timeFrame: 24 weeks
measure: Variation of the result in the Epworth scale
timeFrame: 24 weeks
measure: Variation of the result in the COLUMBIA-SUICIDE SEVERITY RATING (CSSR) scale
timeFrame: 24 weeks
measure: Magnetic Resonance Imagigng (MRI) analysis for 10 of the patients recruited at the Costa del Sol Hospital (pilot subestudy)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Marbella
country: Spain
facility: Costa del Sol University Hospital
state: Málaga
city: Barcelona
country: Spain
facility: Clínic University Hospital
city: Madrid
country: Spain
facility: San Carlos Clinical Hospital
Study officials:
affiliation: SAS
name: Julian Olalla, PhD
role: STUDY_DIRECTOR
References: