Hepatitis C
Conditions
Brief summary
The hypothesis of this study is that pegylated interferon would cause cognitive deficits and mood changes in hepatitis C (HCV) positive subjects.
Detailed description
Subjects with non-cirrhotic hepatitis C will have a magnetic resonance imaging (MRI)/magnetic resonance (MR) spectroscopy and neuropsychological testing prior to starting interferon. Subjects will have repeat testing following 12 weeks of interferon therapy and again at 12 weeks post interferon therapy. MR spectroscopy (MRS) will measure the cerebral metabolites, NAA (N-acetyl aspartate), Cho (choline), MI (myoinositol) and Cr (creatine) at 3 distinct brain regions, i.e. basal ganglia and 2 locations within the frontal cortex. Neuropsychological testing will include tests of the following cognitive domains: executive functioning, memory, language, motor skills and will also include questionnaires pertaining to quality of life (SF-36), mood (Beck's depression inventory) and a self-rating cognitive questionnaire (Conners' Adult Attention Deficit Hyperactivity Disorder Rating Scales \[CAARS\]). Control subjects will include non-cirrhotic HCV subjects who are not taking interferon therapy.
Interventions
DIAGNOSTIC_TESTMR brain and neuropsychiatric tests
Sponsors
Schering-Plough
Beth Israel Deaconess Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults (\>18 years old) of both sexes with chronic HCV infection (all genotypes). * Subjects due to start treatment with pegylated interferon-alpha (IFN-a) for HCV eradication. * Subjects with chronic hepatitis C who have elected not to be treated with pegylated-IFN-a * Subjects with mild fibrosis on liver biopsy (stage 0-III/IV fibrosis) * Subjects able to give informed consent. * Subjects with controlled depression currently taking anti-depressant medication.
Exclusion criteria
* Subjects with cirrhosis on liver biopsy. * Subjects with active alcohol or drug abuse. * Subjects co-infected with human immunodeficiency virus (HIV). * Subjects with structural brain abnormality, past history of cerebrovascular accident (CVA) or serious head trauma. * Subjects with seizure disorder. * Subjects with any contraindication to IFN therapy. * Subjects with a poor command of the English language. * Subjects with a contraindication to MRI, e.g. pacemaker, claustrophobia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | 18 months overall with measures performed at baseline (T1), week 12 (T2) and 12 weeks after end of treatment (T3) with PEG-IFN for 48 weeks which is 60 weeks post baseline | Evaluation of changes in MR spectroscopy. reductions in ratio of Cho and MI reflect improvements in cerebral inflammation and improvement in cognition. Increases in the NAA ratio are suggestive of improvement in cognitive function. |
| Neurocognitive Tests for Cerebral Function | 18 months overall with measures performed at baseline (T1), week 12 (T2) and 12 weeks after end of treatment (T3) with PEG-IFN for 48 weeks which is 60 weeks post baseline and only done in treated group and not controls | A battery of pen and paper neurocognitive tests where subject means are reported compared to the normative Z score. Data is reported at baseline (T1), week 12 on treatment (T2) and 12 weeks after treatment (week 60, T3). Improvements are increases in the test result compared to baseline as determined against the Z score. tests performed included Hopkins learning trials (HVLT), a measure of of verbal learning and memory and the Roy-Osterrieth Complex figure test (ROCF) which evaluates visio-spatal abilities, memory, planning and working memory. Improvements in the score (increases in value compared, either less negative or more positive to the Z score) shown in the table are reflective of improvements in these neurocognitive parameters. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Interferon Treated Group Group treated with PEG-Interferon and ribavirin and undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests | 15 |
| Non-treated Cohort Control Group undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests | 7 |
| Total | 22 |
Baseline characteristics
| Characteristic | Interferon Treated Group | Non-treated Cohort Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 7 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 6 Participants | 19 Participants |
| Region of Enrollment United States | 15 participants | 7 participants | 22 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 7 |
| other Total, other adverse events | 0 / 15 | 0 / 7 |
| serious Total, serious adverse events | 1 / 15 | 0 / 7 |
Outcome results
Primary
Neurocognitive Tests for Cerebral Function
A battery of pen and paper neurocognitive tests where subject means are reported compared to the normative Z score. Data is reported at baseline (T1), week 12 on treatment (T2) and 12 weeks after treatment (week 60, T3). Improvements are increases in the test result compared to baseline as determined against the Z score. tests performed included Hopkins learning trials (HVLT), a measure of of verbal learning and memory and the Roy-Osterrieth Complex figure test (ROCF) which evaluates visio-spatal abilities, memory, planning and working memory. Improvements in the score (increases in value compared, either less negative or more positive to the Z score) shown in the table are reflective of improvements in these neurocognitive parameters.
Time frame: 18 months overall with measures performed at baseline (T1), week 12 (T2) and 12 weeks after end of treatment (T3) with PEG-IFN for 48 weeks which is 60 weeks post baseline and only done in treated group and not controls
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interferon Treated Group | Neurocognitive Tests for Cerebral Function | HVLT, Verbal Learning Total, T1 | -1.43 Z-score | Standard Deviation 0.78 |
| Interferon Treated Group | Neurocognitive Tests for Cerebral Function | HVLT, Verbal Learning Total, T2 | -0.78 Z-score | Standard Deviation 1.3 |
| Interferon Treated Group | Neurocognitive Tests for Cerebral Function | HVLT, Verbal Learning Total, T3 | -0.7 Z-score | Standard Deviation 0.79 |
| Interferon Treated Group | Neurocognitive Tests for Cerebral Function | ROCF, T1 | 0.34 Z-score | Standard Deviation 0.49 |
| Interferon Treated Group | Neurocognitive Tests for Cerebral Function | ROCF, T2 | 0.15 Z-score | Standard Deviation 0.77 |
| Interferon Treated Group | Neurocognitive Tests for Cerebral Function | ROCF,T3 | 0.33 Z-score | Standard Deviation 0.52 |
| Non-treated Cohort Control | Neurocognitive Tests for Cerebral Function | ROCF, T2 | 0.05 Z-score | Standard Deviation 1.22 |
| Non-treated Cohort Control | Neurocognitive Tests for Cerebral Function | HVLT, Verbal Learning Total, T1 | -2.0 Z-score | Standard Deviation 1.01 |
| Non-treated Cohort Control | Neurocognitive Tests for Cerebral Function | ROCF, T1 | -1.0 Z-score | Standard Deviation 1.31 |
| Non-treated Cohort Control | Neurocognitive Tests for Cerebral Function | HVLT, Verbal Learning Total, T2 | -1.16 Z-score | Standard Deviation 0.79 |
| Non-treated Cohort Control | Neurocognitive Tests for Cerebral Function | ROCF,T3 | NA Z-score | — |
| Non-treated Cohort Control | Neurocognitive Tests for Cerebral Function | HVLT, Verbal Learning Total, T3 | NA Z-score | — |
Comparison: Comparison between controls and IFN treated at time point 1 on change between scores for HVLTp-value: >0.05Wilcoxon (Mann-Whitney)
Comparison: Comparison between controls and IFN treated at time point 1 on change between scores for ROCFp-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Comparison between controls and IFN treated at time point 2 on change between scores for HVLTp-value: >0.05Wilcoxon (Mann-Whitney)
Comparison: Comparison between controls and IFN treated at time point 2 on change between scores for ROCFp-value: >0.05Wilcoxon (Mann-Whitney)
Primary
Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex
Evaluation of changes in MR spectroscopy. reductions in ratio of Cho and MI reflect improvements in cerebral inflammation and improvement in cognition. Increases in the NAA ratio are suggestive of improvement in cognitive function.
Time frame: 18 months overall with measures performed at baseline (T1), week 12 (T2) and 12 weeks after end of treatment (T3) with PEG-IFN for 48 weeks which is 60 weeks post baseline
Population: One patient dropped out secondary to claustrophobia and was unable to complete MR portion of study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T2, Cho/Cr | 0.26 ratio | Standard Deviation 0.03 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T3, MI/Cr | 0.71 ratio | Standard Deviation 0.36 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T2. MI/C | 0.71 ratio | Standard Deviation 0.11 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T1, NAA/Cr | 1.73 ratio | Standard Deviation 0.29 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T3, Cho/Cr | 0.29 ratio | Standard Deviation 0.06 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T2, NAA/Cr | 1.74 ratio | Standard Deviation 0.25 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia,T2, Cho/Cr | 0.28 ratio | Standard Deviation 0.05 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T3, NAA/Cr | 1.75 ratio | Standard Deviation 0.37 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T1, NAA/Cr | 1.26 ratio | Standard Deviation 0.27 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T1, Cho/Cr | 0.31 ratio | Standard Deviation 0.14 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T3, MI/C | 0.75 ratio | Standard Deviation 0.13 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T2, Cho/Cr | 0.25 ratio | Standard Deviation 0.04 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T2, NAA/Cr | 1.25 ratio | Standard Deviation 0.03 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T3, Cho/Cr | 0.26 ratio | Standard Deviation 0.04 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia, T1, MI/Cr | 0.78 ratio | Standard Deviation 0.19 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T1, MI/Cr | 0.79 ratio | Standard Deviation 0.19 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T3, NAA/Cr | 1.09 ratio | Standard Deviation 0.17 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T2, MI/Cr | 0.75 ratio | Standard Deviation 0.22 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T1, Cho/Cr | 0.29 ratio | Standard Deviation 0.12 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T3/ MI/Cr | 0.93 ratio | Standard Deviation 0.41 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T1,Mi/Cr | 0.68 ratio | Standard Deviation 0.14 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T1, NAA/Cr | 1.72 ratio | Standard Deviation 0.43 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia, T3, Cho/Cr | 0.34 ratio | Standard Deviation 0.18 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T2, NAA/Cr | 1.65 ratio | Standard Deviation 0.28 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T2, MI/Cr | 0.75 ratio | Standard Deviation 0.32 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLFPC T3, NAA/Cr | 1.78 ratio | Standard Deviation 0.28 |
| Interferon Treated Group | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia, T1, Cho/Cr | 0.42 ratio | Standard Deviation 0.26 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLFPC T3, NAA/Cr | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia, T1, Cho/Cr | 0.30 ratio | Standard Deviation 0.04 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia,T2, Cho/Cr | 0.28 ratio | Standard Deviation 0.05 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia, T3, Cho/Cr | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia, T1, MI/Cr | 0.78 ratio | Standard Deviation 0.19 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T2. MI/C | 0.72 ratio | Standard Deviation 0.21 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T3, MI/C | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T1, Cho/Cr | 0.28 ratio | Standard Deviation 0.03 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T2, Cho/Cr | 0.29 ratio | Standard Deviation 0.08 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T3, Cho/Cr | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T1, NAA/Cr | 1.28 ratio | Standard Deviation 0.54 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T2, NAA/Cr | 1.07 ratio | Standard Deviation 0.13 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Basal Ganglia T3, NAA/Cr | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T1,Mi/Cr | 0.77 ratio | Standard Deviation 0.23 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T2, MI/Cr | 1.19 ratio | Standard Deviation 0.68 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T3, MI/Cr | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T1, NAA/Cr | 1.55 ratio | Standard Deviation 0.49 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T2, NAA/Cr | 1.72 ratio | Standard Deviation 0.67 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | Frontal Cortex T3, NAA/Cr | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T1, Cho/Cr | 0.27 ratio | Standard Deviation 0.05 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T2, Cho/Cr | 0.27 ratio | Standard Deviation 0.06 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T3, Cho/Cr | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T1, MI/Cr | 0.78 ratio | Standard Deviation 0.18 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T2, MI/Cr | 0.86 ratio | Standard Deviation 0.13 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T3/ MI/Cr | NA ratio | — |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T1, NAA/Cr | 1.61 ratio | Standard Deviation 0.31 |
| Non-treated Cohort Control | Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex | DLPFC T2, NAA/Cr | 1.60 ratio | Standard Deviation 0.29 |
Comparison: Within group comparison of IFN group for metabolites in basal ganglia Comparison on MR spectroscopy of Cho/Cr at time points 1,2 and 3p-value: 0.08Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of IFN group for metabolites in basal ganglia Comparison on MR spectroscopy of Mi/Cr at time points 1,2 and 3p-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of IFN group for metabolites in basal ganglia Comparison on MR spectroscopy of NAA/Cr at time points 1,2 and 3p-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of IFN group for metabolites in frontal cortex. Comparison on MR spectroscopy of Cho/Cr at time points 1,2 and 3p-value: 0.7Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of IFN group for metabolites in frontal cortex. Comparison on MR spectroscopy of MI/Cr at time points 1,2 and 3p-value: 0.4Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of IFN group for metabolites in frontal cortex. Comparison on MR spectroscopy of NAA/Cr at time points 1,2 and 3p-value: 0.6Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of IFN group for metabolites in DLPFC. Comparison on MR spectroscopy of Cho/Cr at time points 1,2 and 3p-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of IFN group for metabolites in DLPFC. Comparison on MR spectroscopy ofMI/Cr at time points 1,2 and 3p-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of IFN group for metabolites in DLPFC. Comparison on MR spectroscopy of NAA/Cr at time points 1,2 and 3p-value: 0.3Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in Basal ganglia. Comparison on MR spectroscopy of Cho/Cr at time points 1 and 2p-value: 0.4Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in Basal ganglia. Comparison on MR spectroscopy of MI/Cr at time points 1 and 2p-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in Basal ganglia. Comparison on MR spectroscopy of NAA/Cr at time points 1 and 2p-value: 0.6Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in frontal cortex. Comparison on MR spectroscopy of Cho/Cr at time points 1 and 2p-value: 0.7Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in frontal cortex. Comparison on MR spectroscopy of MI/Cr at time points 1 and 2p-value: 0.1Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in frontal cortex. Comparison on MR spectroscopy of NAA/Cr at time points 1 and 2p-value: 0.6Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in DLPFC. Comparison on MR spectroscopy of Cho/Cr at time points 1 and 2p-value: 0.5Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in DLPFC. Comparison on MR spectroscopy of MI/Cr at time points 1 and 2p-value: 0.4Wilcoxon (Mann-Whitney)
Comparison: Within group comparison of control group for metabolites in DLPFC. Comparison on MR spectroscopy of NAA/Crat time points 1 and 2p-value: 0.9Wilcoxon (Mann-Whitney)