Cognitive Impairments in Chronic Hepatitis C Patients and Potential Reversibility With New Agents (CICHepC)

Hepatitis C Clinical Trial

— CICHepC  

Official title:

Personalized Medicine in HCV Infection: Cognitive Impairments and Brain Anomalies in Chronic Hepatitis C Infected Individuals. Characterization and Potential Reversibility With Direct Antiviral Agents.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02745132
• Other study ID #: CICHepC-PIE15/00079-JCG
• Secondary ID: PIE15/00079
• Status: Not yet recruiting
• Phase: Phase 4
• First received: April 10, 2016
• Last updated: April 19, 2016
• Start date: June 2016
• Est. completion date: December 2017

Study information

• Verified date: April 2016
• Source: Instituto de Investigación Marqués de Valdecilla
• Contact: Javier Crespo García, MDPhD
• Phone: 34 942 202544
• Email: javiercrespo1991[@]gmail.com
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

The overall aim of this study is to evaluate the prevalence of cognitive impairments and brain anomalies in Chronic Hepatitis C infected individuals and to investigate likely changes in cognition and brain structure and function after treatment with Direct-acting Antivirals (DAAs).

Description:

Design: Prospective interventional study.

Chronic HCV infected patients who are going to initiate a DAA-based antiviral regimen according to clinical practice will be recruited to participate in the study. Patients will be treated according to the current national and international guidelines for the treatment of HCV chronic hepatitis. The participation in the study will not influence neither the indication for de treatment nor the type of treatment prescribed. The only intervention in this study refers to the performance of extraordinary neuro-psychological evaluations and MRI studies at different times along the study.

Patients and methods:

This study will be performed in a cohort of 80 patients with CHC (≤ F3). The number of subjects required to test effects with sufficient power over the entire cortex varies between cortical measures (cortical thickness: N=39, surface area: N=21, volume: N=81; 10mm smoothing, power=0.8, α =0.05). For subcortical regions this number is between 16 and 76 subjects, depending on the region (Liem et al., 2015). Sample size calculations performed for functional magnetic resonance using values of medium Cohen's d effect size of 0.6 and 0.7 yield sample sizes of 88, 66 respectively to achieve 80% power at a significance level of 0.05 (Guo et al., 2012). Therefore, the sample size estimated in this project would yield enough power to detect small and medium effects size.

The following studies will be conducted:

1. - Cognitive assessment: The assessment with widely-used neuropsychological test batteries may yield summary scores for the domains: attention and reaction time (Continuous Performance Test (CPT), working memory (digits forward and backward WAIS-III subtest), information processing speed (digit symbol WAIS-III subtest and Trail making test Part A), verbal fluency (letter FAS and category animals subtest), learning and memory (Rey Auditory 2.- Verbal Learning Test (RAVLT) and Rey Copy Figure(RCF)), motor functioning (Grooved Pegboard) and executive functions (Tower of London, Trail making test Part B and Stroop color-word test).

2. - MRI scanning: Imaging data will be acquired at the neurorradiology section of the Hospital Marques de Valdecilla, on a 3T MRI scanner (Achieva, Philips Medical Systems, Best, The Netherlands) at the Neuroradiology Department of "Marques de Valdecilla" University Hospital. Subjects will undergo a 30 minutes protocol that will include a high resolution T1- weighted image, a 64 directions DWI sequence and A BOLD resting state fMRI sequence.

3. - MRI data analysis: It will involve structural, diffusion and functional MRI analyses. These analyses will be conducted by Neuroimaging Platform at the IDIVAL.

3.1.- Structural MRI: we will use the software FreeSurfer (http://freesurfer.net/) to quantify the volume of subcortical structures (amygdala, hippocampus, thalamus, putamen, globus pallidus, and caudate nucleus) and the area, thickness, and volume of 34 cortical structures (Desikan-Killiany atlas).

3.2.- Diffusion MRI: we will use FSL's TBSS and Probtracx tools http://www.fmrib.ox.ac.uk/fsl/index.html) to compare fractional anisotropy values (a measure based on restricted movement of water molecules) in whole brain voxelwise analysis and identify regions (clusters) where white matter is more disorganized.

Also we will perform fiber tracking and study connectivity between different brain areas.

3.3.- Functional MRI (fMRI): resting state fmri will be used to evaluate regional interactions that occur when non performing and specific task. This analysis will be carried out with using SPM software http://www.fil.ion.ucl.ac.uk/spm/) and the toolbox PRONTO (http://www.mlnl.cs.ucl.ac.uk/pronto ).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• CHC patients 18-75 years old

• Liver fibrosis = F3 in Fibroscan/liver biopsy

• Naive or previous failure to a treatment

• Accept the study and sign the CI

Exclusion Criteria:

• Does not meet the above criteria

• VIH or other viral coinfection

• Hepatocarcinoma

• Other systemic inflammatory diseases (i.e. RA, etc)

• Neurodegenerative diseases

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Cognition Disorders
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Other:
• Neuropsychological evaluation and Brain MRI
This is a prospective study. The only intervention planned will consist of performing neuropsychological tests and cerebral MRI that will be carried out on a single group cohort at different times. Notwithstanding, we will record the exposure to DAA to assess any change in neurocognitive function and MRI imaging. Anti-HCV regimens will be used according to clinical practice as indicated into the current guidelines (1) (1)European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol. 2015 Jul;63(1):199-236. doi: 10.1016/j.jhep.2015.03.025. Epub 2015 Apr 21. PubMed PMID: 25911336.

Locations

Country	Name	City	State
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria

Sponsors (2)

Lead Sponsor	Collaborator
Instituto de Investigación Marqués de Valdecilla	Ministerio de Economía y Competitividad, Spain

Country where clinical trial is conducted

Spain, 

References & Publications (4)

Bajaj JS, Forton DM. Cognitive improvement after HCV eradication: Extending the benefits. Hepatology. 2013 Aug;58(2):480-2. doi: 10.1002/hep.26481. Epub 2013 Jun 25. — View Citation

Byrnes V, Miller A, Lowry D, Hill E, Weinstein C, Alsop D, Lenkinski R, Afdhal NH. Effects of anti-viral therapy and HCV clearance on cerebral metabolism and cognition. J Hepatol. 2012 Mar;56(3):549-56. doi: 10.1016/j.jhep.2011.09.015. Epub 2011 Oct 23. — View Citation

Fletcher NF, Wilson GK, Murray J, Hu K, Lewis A, Reynolds GM, Stamataki Z, Meredith LW, Rowe IA, Luo G, Lopez-Ramirez MA, Baumert TF, Weksler B, Couraud PO, Kim KS, Romero IA, Jopling C, Morgello S, Balfe P, McKeating JA. Hepatitis C virus infects the endothelial cells of the blood-brain barrier. Gastroenterology. 2012 Mar;142(3):634-643.e6. doi: 10.1053/j.gastro.2011.11.028. Epub 2011 Dec 1. — View Citation

Kraus MR, Schäfer A, Teuber G, Porst H, Sprinzl K, Wollschläger S, Keicher C, Scheurlen M. Improvement of neurocognitive function in responders to an antiviral therapy for chronic hepatitis C. Hepatology. 2013 Aug;58(2):497-504. doi: 10.1002/hep.26229. Epub 2013 Jun 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Continuous Performance Test (CPT) score	Neuropsychological test to assess Cognitive impairment, particularly Attention and reaction time	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Digits forward and backward WAIS-III subtest scores	Neuropsychological test to assess Cognitive impairment, particularly Working memory	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Digit symbol WAIS-III subtest score	Neuropsychological test to assess Information processing speed	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Trail Making Test (TMT) Parts A & B scores	Neuropsychological test to assess Information processing speed	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Letter FAS score	Neuropsychological test to assess Verbal fluency	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in animal category subtest score	Neuropsychological test to assess Verbal fluency	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Rey Auditory Verbal Learning Test (RAVLT) scores	Neuropsychological test to assess Learning and memory	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Rey Copy Figure(RCF) scores	Neuropsychological test to assess Learning and memory	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Grooved Pegboard score	Neuropsychological test to assess Motor functioning	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Tower of London score	Neuropsychological test to assess Executive functions	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in Stroop color-word test scores	Neuropsychological test to assess Executive functions	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in cortical thickness	Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in cortical surface área assessed by MRI	Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Changes in cortical surface volumen assessed by MRI	Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).	Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Sustained Viral Response	Data on efficacy of treatments	3, 6 and 12 months after the end of treatment (Sustained Viral Response)	No
Secondary	Advers events	Data on safety	up to 24 weeks	Yes