Neuropsyquiatric Evolution After Introduction of Raltegravir QD in Substitution of Dolutegravir: NEAR QD Study

HIV Infections Clinical Trial

— NEARQD  

Official title:

Neuropsyquiatric Evolution After Introduction of Raltegravir QD in Substitution of Dolutegravir: NEAR QD Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03732625
• Other study ID #: FIMHCSBR-2017
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2019
• Est. completion date: January 2021

Study information

• Verified date: December 2018
• Source: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Contact: Gloria Luque
• Phone: +34 951 29 19 77
• Email: gloria.luque[@]fimabis.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open, multicenter, non randomized, single arm, pilot trial.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: January 2021
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Raltegravir
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.

Locations

Country	Name	City	State
Spain	Clínic University Hospital	Barcelona
Spain	San Carlos Clinical Hospital	Madrid
Spain	Costa del Sol University Hospital	Marbella	Málaga

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate improvement in neuropsychiatric symptoms at 12 weeks (Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events)	Evaluate improvement in neuropsychiatric symptoms: grade 1 to 4 of DAIDS scale. higher values represent a worse outcome	12 weeks
Secondary	Neuropsychiatric symptoms	Presence and Intensity of neuropsychiatric symptoms (visual scale 0 to 10)	24 weeks
Secondary	Interruptions of the medication for any reason	Interruptions of the medication due to adverse effects, virological failure, or any other reason	24 weeks
Secondary	Change in quality of life (WHOQoL-bref questionnaire)	World Health Organization Quality of Life: 1-100 in 4 domains. 100 best score	24 weeks
Secondary	Variation of the result in the Hospital, Anxiety and Depression (HAD) scale	Hospital, anxiety and depression: 0 y 7 indicates no case, between 8 & 10 indicates doubtful case and scores of 11 and above are possibly anxiety and depression cases.	24 weeks
Secondary	Variation of the result on the Pittsburgh Sleep Quality Index (PSQI) scale	Pittsburgh Sleep Quality Index: Score 0 to 21 points. "0" indicates ease of sleeping and "21" severe difficulty in all areas.	24 weeks
Secondary	Variation of the result in the Epworth scale	Diurnal drowsiness: If score is less than 6 points, daytime sleepiness is low or absent; between 7 and 8, is in the average of the population and if it is higher than 9 its drowsiness is excessive.	24 weeks
Secondary	Variation of the result in the COLUMBIA-SUICIDE SEVERITY RATING (CSSR) scale	COLUMBIA-SUICIDE SEVERITY RATING SCALE: progressive score depending of each question answer	24 weeks
Secondary	Magnetic Resonance Imagigng (MRI) analysis for 10 of the patients recruited at the Costa del Sol Hospital (pilot subestudy)	Identify patterns of different metabolic marker 18F-fluorodeoxyglucose (18F-FDG) uptake in patients suffering from central nervous system toxicity in relation to the use of Dolutegravir after replacement with Raltegravir.; Observe if the anatomic-functional pattern of these patients changes after the substitution of Dolutegravir by Raltegravir.	24 weeks