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

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

Study Overview

• Status: Unknown
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Raltegravir

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • CLINIC UNIVERSITY HOSPITAL
  • Madrid, Spain, 28040
    • San Carlos Clinical Hospital
  • Málaga
    • Marbella, Málaga, Spain, 29603
      • Costa del Sol University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltegravir; Raltegravir (RAL) x 2 600mg QD (Total 1200mg QD)	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.; Other Names: Substitution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychiatric symptoms	Presence and Intensity of neuropsychiatric symptoms (visual scale 0 to 10)	24 weeks
Interruptions of the medication for any reason	Interruptions of the medication due to adverse effects, virological failure, or any other reason	24 weeks
Change in quality of life (WHOQoL-bref questionnaire)	World Health Organization Quality of Life: 1-100 in 4 domains. 100 best score	24 weeks
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Julian Olalla, PhD, SAS

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2019
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: November 2, 2018
• First Submitted That Met QC Criteria: November 5, 2018
• First Posted (Actual): November 6, 2018

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: HIV infection; Raltegravir; neuropsychological adverse effects
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: FIMHCSBR-2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No