Trial Outcomes & Findings for Cerebral Effects of Pegylated Interferon in Hepatitis C Positive Subjects (NCT NCT00136214)
NCT ID: NCT00136214
Last Updated: 2018-07-12
Results Overview
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.
Recruitment status
COMPLETED
Target enrollment
22 participants
Primary outcome timeframe
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
Results posted on
2018-07-12
Participant Flow
Participant milestones
| Measure |
Interferon Treated Group
Group treated with PEG-Interferon and ribavirin and undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests
|
Non-treated Cohort Control
Group undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
7
|
|
Overall Study
COMPLETED
|
15
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cerebral Effects of Pegylated Interferon in Hepatitis C Positive Subjects
Baseline characteristics by cohort
| Measure |
Interferon Treated Group
n=15 Participants
Group treated with PEG-Interferon and ribavirin and undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests
|
Non-treated Cohort Control
n=7 Participants
Group undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
7 participants
n=7 Participants
|
22 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 baselinePopulation: One patient dropped out secondary to claustrophobia and was unable to complete MR portion of study
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.
Outcome measures
| Measure |
Interferon Treated Group
n=14 Participants
Group treated with PEG-Interferon and ribavirin and undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests Significant reductions in basal ganglia Cho/Cr (p = 0.03) and basal ganglia MI/Cr (p = 0.03) were observed in sustained virological responders (SVRs, n = 8), but not non-responders/ relapsers (NR/R, n = 6), indicative of reduced cerebral infection and/or immune activation in those who cleared virus. SVRs demonstrated significant improvements in verbal learning, memory, and visuo-spatial memory.
|
Non-treated Cohort Control
n=7 Participants
Group undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests
A small but significant improvement in neurocognitive function secondary to the practice effect was seen in both HCV controls and HCV subjects during treatment.
|
|---|---|---|
|
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
|
0.30 ratio
Standard Deviation 0.04
|
|
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
|
0.28 ratio
Standard Deviation 0.05
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
|
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
|
0.28 ratio
Standard Deviation 0.03
|
|
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
|
0.27 ratio
Standard Deviation 0.05
|
|
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
|
0.27 ratio
Standard Deviation 0.06
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
|
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
|
0.86 ratio
Standard Deviation 0.13
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
|
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
|
0.78 ratio
Standard Deviation 0.19
|
|
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
|
0.72 ratio
Standard Deviation 0.21
|
|
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
|
0.29 ratio
Standard Deviation 0.08
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
|
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
|
1.28 ratio
Standard Deviation 0.54
|
|
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
|
1.07 ratio
Standard Deviation 0.13
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
|
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
|
0.77 ratio
Standard Deviation 0.23
|
|
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
|
1.19 ratio
Standard Deviation 0.68
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
|
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
|
1.55 ratio
Standard Deviation 0.49
|
|
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
|
1.72 ratio
Standard Deviation 0.67
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
|
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
|
0.78 ratio
Standard Deviation 0.18
|
|
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
|
1.61 ratio
Standard Deviation 0.31
|
|
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
|
1.60 ratio
Standard Deviation 0.29
|
|
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
|
NA ratio
Standard Deviation NA
time point not done as per protocol
|
PRIMARY outcome
Timeframe: 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 controlsA 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.
Outcome measures
| Measure |
Interferon Treated Group
n=15 Participants
Group treated with PEG-Interferon and ribavirin and undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests Significant reductions in basal ganglia Cho/Cr (p = 0.03) and basal ganglia MI/Cr (p = 0.03) were observed in sustained virological responders (SVRs, n = 8), but not non-responders/ relapsers (NR/R, n = 6), indicative of reduced cerebral infection and/or immune activation in those who cleared virus. SVRs demonstrated significant improvements in verbal learning, memory, and visuo-spatial memory.
|
Non-treated Cohort Control
n=7 Participants
Group undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests
A small but significant improvement in neurocognitive function secondary to the practice effect was seen in both HCV controls and HCV subjects during treatment.
|
|---|---|---|
|
Neurocognitive Tests for Cerebral Function
HVLT, Verbal Learning Total, T1
|
-1.43 Z-score
Standard Deviation 0.78
|
-2.0 Z-score
Standard Deviation 1.01
|
|
Neurocognitive Tests for Cerebral Function
ROCF, T2
|
0.15 Z-score
Standard Deviation 0.77
|
0.05 Z-score
Standard Deviation 1.22
|
|
Neurocognitive Tests for Cerebral Function
HVLT, Verbal Learning Total, T2
|
-0.78 Z-score
Standard Deviation 1.3
|
-1.16 Z-score
Standard Deviation 0.79
|
|
Neurocognitive Tests for Cerebral Function
HVLT, Verbal Learning Total, T3
|
-0.7 Z-score
Standard Deviation 0.79
|
NA Z-score
Standard Deviation NA
not performed at time point 3 as per protocol
|
|
Neurocognitive Tests for Cerebral Function
ROCF, T1
|
0.34 Z-score
Standard Deviation 0.49
|
-1.0 Z-score
Standard Deviation 1.31
|
|
Neurocognitive Tests for Cerebral Function
ROCF,T3
|
0.33 Z-score
Standard Deviation 0.52
|
NA Z-score
Standard Deviation NA
not performed at time point 3 as per protocol
|
Adverse Events
Interferon Treated Group
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Non-treated Cohort Control
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Interferon Treated Group
n=15 participants at risk
Group treated with PEG-Interferon and ribavirin and undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests
|
Non-treated Cohort Control
n=7 participants at risk
Group undergoing MR brain and neuropsychiatric tests
MR brain and neuropsychiatric tests
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Fatigue, fu like symptoms
|
6.7%
1/15 • Number of events 1 • 18 months
|
0.00%
0/7 • 18 months
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place