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

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ClinicalTrials.gov Identifier: NCT02745132
Recruitment Status : Unknown
Verified April 2016 by Instituto de Investigación Marqués de Valdecilla.
Recruitment status was:  Not yet recruiting
First Posted : April 20, 2016
Last Update Posted : April 21, 2016
Sponsor:
Collaborator:
Ministerio de Economía y Competitividad, Spain
Information provided by (Responsible Party):
Instituto de Investigación Marqués de Valdecilla

Tracking Information
First Submitted Date  ICMJE April 10, 2016
First Posted Date  ICMJE April 20, 2016
Last Update Posted Date April 21, 2016
Study Start Date  ICMJE June 2016
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2016)
Changes in Continuous Performance Test (CPT) score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
Neuropsychological test to assess Cognitive impairment, particularly Attention and reaction time
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
  • Changes in Digits forward and backward WAIS-III subtest scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Cognitive impairment, particularly Working memory
  • Changes in Digit symbol WAIS-III subtest score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Information processing speed
  • Changes in Trail Making Test (TMT) Parts A & B scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Information processing speed
  • Changes in Letter FAS score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Verbal fluency
  • Changes in animal category subtest score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Verbal fluency
  • Changes in Rey Auditory Verbal Learning Test (RAVLT) scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Learning and memory
  • Changes in Rey Copy Figure(RCF) scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Learning and memory
  • Changes in Grooved Pegboard score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Motor functioning
  • Changes in Tower of London score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Executive functions
  • Changes in Stroop color-word test scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Executive functions
  • Changes in cortical thickness [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).
  • Changes in cortical surface área assessed by MRI [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).
  • Changes in cortical surface volumen assessed by MRI [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).
  • Sustained Viral Response [ Time Frame: 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Data on efficacy of treatments
  • Advers events [ Time Frame: up to 24 weeks ]
    Data on safety
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2016)
  • Changes in Digits forward and backward WAIS-III subtest scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Cognitive impairment, particularly Working memory
  • Changes in Digit symbol WAIS-III subtest score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Information processing speed
  • Changes in Trail Making Test (TMT) Parts A & B scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Information processing speed
  • Changes in Letter FAS score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Verbal fluency
  • Changes in animal category subtest score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Verbal fluency
  • Changes in Rey Auditory Verbal Learning Test (RAVLT) scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Learning and memory
  • Changes in Rey Copy Figure(RCF) scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Learning and memory
  • Changes in Grooved Pegboard score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Motor functioning
  • Changes in Tower of London score [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Executive functions
  • Changes in Stroop color-word test scores [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Neuropsychological test to assess Executive functions
  • Changes in cortical thickness [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).
  • Changes in cortical surface área assessed by MRI [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).
  • Changes in cortical surface volumen assessed by MRI [ Time Frame: Basal and 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Basal Neuroimaging findings in HCV infected patients and changes after DAA treatment (Assesed through structural, diffusion and functional MRI).
  • Sustained Viral Response [ Time Frame: 3, 6 and 12 months after the end of treatment (Sustained Viral Response) ]
    Data on efficacy of treatments
  • Advers events [ Time Frame: Assessed at different moments along the treatment ]
    Data on safety
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cognitive Impairments in Chronic Hepatitis C Patients and Potential Reversibility With New Agents (CICHepC)
Official Title  ICMJE Personalized Medicine in HCV Infection: Cognitive Impairments and Brain Anomalies in Chronic Hepatitis C Infected Individuals. Characterization and Potential Reversibility With Direct Antiviral Agents.
Brief 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).
Detailed 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 ).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Condition  ICMJE Hepatitis C
Intervention  ICMJE 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.

Study Arms  ICMJE Cognitive evaluation in HCV patients

Neuropsychological evaluation and Brain MRI

Intervention: The only intervention to be carried out along the study will consist of complete neuro-psychological tests and MRI studies performed at different times.

Chronic HCV patients who are going to be treated with new DAAs according to current guidelines will be studied: A neuro-psychological battery of tests and brain MRI studies will be performed at different times before and after the end of the treatment. The participation in the study will not influence neither the indication to treat nor the treatment used.

Anti-HCV regimens will be used according to clinical practice as indicated into the current guidelines

Intervention: Other: Neuropsychological evaluation and Brain MRI
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: April 15, 2016)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02745132
Other Study ID Numbers  ICMJE CICHepC-PIE15/00079-JCG
PIE15/00079 ( Other Grant/Funding Number: Ministerio de Economía y Competitividad, Spain )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Instituto de Investigación Marqués de Valdecilla
Study Sponsor  ICMJE Instituto de Investigación Marqués de Valdecilla
Collaborators  ICMJE Ministerio de Economía y Competitividad, Spain
Investigators  ICMJE
Principal Investigator: Javier Crespo García, MDPhD Head of Gastroenterology and Hepatology at Hospital Universitario Marqués de Valdecilla. Professor at the Universidad de Cantabria
Principal Investigator: Benedicto Crespo Facorro, MDPhD Head of section Of Psychiatry at University Hospital Marqués de Valdecilla. Proffesor of Psychiatry at Department of Psychiatry, School of Medicine
PRS Account Instituto de Investigación Marqués de Valdecilla
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP