Changes in Cognition in HCV Patients After Virus Eradication With Direct Antiviral Agents

Changes in Cognition in HCV Patients After Virus Eradication With Direct Antiviral Agents. Relationship With Clinical and Sociodemographic Variables

Study about the improvement of cognitive, psychopathological and functional abilities in Hepatitis C Virus (HCV) infected patients after eradication of the virus with direct antiviral agents.

Study Overview

• Status: Completed
• Conditions: HCV Coinfection; HCV Infection

Detailed Description

The aim of this study is to investigate the effect that the eradication of the HCV has on cognition, quality of life and psychopathology. At the same time, investigators intend to study the association between cognitive changes and some clinical variables.

The sample consists of 80 subjects (40 HCV patients and 40 HCV patients coinfected with the Human Immunodeficiency Virus, HIV). Exclusion criteria: Cirrhosis, presence of minimal hepatic encephalopathy or active drug consumption.

A neuropsychological assessment is made before the treatment with direct antiviral agents to evaluate memory, executive functions, processing speed, anxiety, depression and quality of life. Additionally, the following clinical variables are collected: Viral charge, immunosuppression (measured with T Cells CD4 (CD4), CD4 nadir and T Cells CD8 (CD8)) and fibrosis level, HCV genotype and plasma biomarkers: Brain-Derived Neurotrophic Factor (BDNF), Interleukine 6 (IL6), Tumor Necrosis Factor (TNF-a),Glial fibrillary acidic protein (GFAP), Soluble CD14 (SCD14), Neuro-specific enolase (NSE).

The second neuropsychological assessment and clinical data collection is carried out after treatment, concretely 6 months after HCV is undetectable in plasma.

• Study Type: Observational
• Enrollment (Actual): 80

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HCV patients who are candidates to direct antiviral treatment

Description

Inclusion Criteria:

• Patients over 18 years old with indication to receive antiviral treatment
• Diagnosis of chronic infection by hepatitis C virus in the fibrous phase F3 or F4 that have not presented any clinical decompensation of their liver disease, with or without HIV co-infection

Exclusion Criteria:

• Active alcohol consumption> 40g daily or history of chronic alcoholism
• Active consumption of other toxics (heroin, cocaine, cannabis)
• Patients with minimum hepatic encephalopathy
• Background of cerebral neurological disease, chronic renal insufficiency and / or psychiatric illnesses assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, which can affect cognitive functions.
• Active use of psychotropics or benzodiazepines

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Memory tests	Rey Auditory Verbal Learning Test (RVLT, Spreen & Strauss 1998) assesses verbal learning, recall and recognition memory; Wechsler Adults Intelligence Scale III backward digits subtest (WAIS, Wechsler 1997) assesses working memory. All direct scores have been transformed into T-scores (mean=50; SD=10), which allows to obtain a single memory component.	baseline, change at 6 months after treatment
Attention tests	Continous Performance Test (CPT, Conners 2000) assesses sustained attention, inattentiveness and impulsivity; WAIS forward digits subtest (WAIS III, Wechsler 1997) assesses attention. All direct scores have been transformed into T-scores (mean=50; SD=10), which allows to obtain a single attention component.	baseline, change at 6 months after treatment
Executive function tests	Stroop Test (Stroop, 1935) assesses flexibility and inhibition of automatic responses; Trail Making Test (TMTA-B Reitan, 1993) assesses visual tracking and flexibility, phonetic and semantic fluency tests (Lezak, 1995) assess verbal fluency; Tower of London (Culbertson & Zillmer, 2005) assesses visual reasoning and planification. All direct scores have been transformed into T-scores (mean=50; SD=10), which allows to obtain a single executive function component.	baseline, change at 6 months after treatment
Speed processing test	Digit symbol test (WAIS III, Wechsler 1997) assesses visuomotor speed. The direct scores have been transformed into T-scores (mean=50; SD=10).	baseline, change at 6 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Anxiety and Depression Scale (HADS)	It is a self-registering scale of 14 items: 7 items evaluating anxiety and 7 items evaluating depression (Zigmond & Snaith, 1983). Scoring range: 0-21 for each subscale. Scores >10 in each subscale imply a significant anxious/depressive symptomatology.	baseline, change at 6 months after treatment
36-Item Short Form Health Survey (SF-36 )	It is a self-registered scale for the assessment of quality of life ( Alonso y cols. , 1995). It consists on 8 dimensions: Physical functioning, limitations for physical issues, corporal pain, social functioning, mental health, limitations for emotional issues, vitality and general perception of the own health. For each dimension, the scoring range goes from 0 to 100, where higher values represent better outcome (better quality of life/less limitations/better functioning).	baseline, change at 6 months after treatment
Fibroscan	Degree of fibrosis: Speed of propagation of elastic waves measured with fibroscan.	Baseline, change at 6 months after treatment
HCV RNA	Viral load quantity measured by plasma HCV RNA is collected in HIV co-infected patients	Baseline, change at 3 months after treatment, change at 6 months after treatment.
Immunosuppression state	The next cells were analyzed in blood, in HIV co-infected patients : CD4, %CD4, nadir CD4, CD8, % CD8, CD4/CD8 ratio.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Biomarkers measures	The next blood biomarkers were collected: Brain-derived neurotrophic factor (BDNF); Interleukine 6 (Il-6); Tumor Necrosis Factor (TNF-a ); Glial fibrillary acidic protein (GFAP); Soluble SCD 14 (sCD14) ; Neuro-specific enolase (NSE).	1 day pretreatment and change at 6 months post treatment

Collaborators and Investigators

• Sponsor: Corporacion Parc Tauli

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2016
• Primary Completion (Actual): September 6, 2017
• Study Completion (Actual): December 15, 2018

Study Registration Dates

• First Submitted: March 28, 2018
• First Submitted That Met QC Criteria: April 16, 2018
• First Posted (Actual): April 25, 2018

Study Record Updates

• Last Update Posted (Actual): February 4, 2019
• Last Update Submitted That Met QC Criteria: February 1, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Coinfection
• Other Study ID Numbers: CIR2015/042