Trial Outcomes & Findings for Lurasidone Effects on Tissue Glutamate in Schizophrenia (NCT NCT02199743)
NCT ID: NCT02199743
Last Updated: 2021-03-01
Results Overview
Mean values of cerebral glutamate levels was measured by high resolution 3T magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC). Data were acquired from the dorsal anterior cingulate cortex (ACC) using single voxel localized PRESS (TE1, TE2) = (32, 65) ms with an 8-channel head coil in a 3T whole-body scanner (Philips Medical Systems). Voxel size was 30x20x15 mm3 (9 mL) and were placed over the bilateral anterior cingulate cortex (ACC). All values are normalized to water. More negative values represent less cerebral glutamate levels.
COMPLETED
PHASE4
35 participants
Baseline and 4 weeks
2021-03-01
Participant Flow
35 individuals initially signed the Informed Consent and began the Screening procedures. Only 24 made it to Randomization, with only 22 making it to the end of the study. Generally participants were discontinued because they were lost to follow-up (which requires 3 telephone calls and a letter) and irregular labs that were exclusionary.
Participant milestones
| Measure |
Lurasidone
Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks
This group was compared to the "Non-Lurasidone" group (with both haloperidol and perphenazine together) in the final analysis.
|
Non-Lurasidone
Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.
OR Perphenazine 8mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.
Each of these drug groups were treated individually in the study but grouped together into a "Non-Lurasidone" group for analysis.
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
10
|
|
Overall Study
COMPLETED
|
14
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Lurasidone Effects on Tissue Glutamate in Schizophrenia
Baseline characteristics by cohort
| Measure |
Lurasidone
n=14 Participants
Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks
Compare to haloperidol and perphenazine groups combined to lurasidone group.
|
Non-Lurasidone
n=10 Participants
Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.
OR Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.
Compare haloperidol and perphenazine groups combined to lurasidone.
|
Total
n=24 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
|
14 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
51 years
n=5 Participants
|
46 years
n=7 Participants
|
49 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=5 Participants
|
8 participants
n=7 Participants
|
22 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 4 weeksPopulation: Of the original 22 participants, only 15 have both Baseline and Week 4 scans to compare.
Mean values of cerebral glutamate levels was measured by high resolution 3T magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC). Data were acquired from the dorsal anterior cingulate cortex (ACC) using single voxel localized PRESS (TE1, TE2) = (32, 65) ms with an 8-channel head coil in a 3T whole-body scanner (Philips Medical Systems). Voxel size was 30x20x15 mm3 (9 mL) and were placed over the bilateral anterior cingulate cortex (ACC). All values are normalized to water. More negative values represent less cerebral glutamate levels.
Outcome measures
| Measure |
Lurasidone
n=8 Participants
Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks
This group was compared to the "Non-Lurasidone" group (with both haloperidol and perphenazine together) in the final analysis.
|
Non-Lurasidone
n=7 Participants
Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.
OR Perphenazine 8mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.
Each of these drug groups were treated individually in the study but grouped together into a "Non-Lurasidone" group for analysis.
|
|---|---|---|
|
Cerebral Glutamate Levels
Baseline (week 0)
|
-1.434662171 relative unit (RU as compared to water)
Standard Deviation 0.741430931
|
-1.933853656 relative unit (RU as compared to water)
Standard Deviation 1.005387144
|
|
Cerebral Glutamate Levels
week 4
|
-1.412294235 relative unit (RU as compared to water)
Standard Deviation 0.952600355
|
-1.838991525 relative unit (RU as compared to water)
Standard Deviation 1.20411535
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: Of the original 22 participants, only 15 have both Baseline and Week 4 to compare.
Mean of cognition was assessed by BACS, which measures neurocognitive function in schizophrenia. BACs is a validated, composite measure of cognition which is used in schizophrenia. It is composed of Verbal memory (range: 0-75), Working memory (range: 0-28), Motor speed (range: 0-100), Verbal Fluency (number of words generated), Information processing (range: 0-110) and Executive functions (range: 0-22). Higher z-scores indicate a better performance and outcome. BACS composite score are represented as z-scores which can be positive or negative. There is no minimum or maximum as this is a continuous measure.
Outcome measures
| Measure |
Lurasidone
n=8 Participants
Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks
This group was compared to the "Non-Lurasidone" group (with both haloperidol and perphenazine together) in the final analysis.
|
Non-Lurasidone
n=7 Participants
Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.
OR Perphenazine 8mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.
Each of these drug groups were treated individually in the study but grouped together into a "Non-Lurasidone" group for analysis.
|
|---|---|---|
|
Brief Assessments of Cognition in Schizophrenia Scores (BACS)
Baseline (week 0)
|
-1.596573107 BACS composite score (z score)
Standard Deviation 0.929835487
|
-1.933853656 BACS composite score (z score)
Standard Deviation 1.005387144
|
|
Brief Assessments of Cognition in Schizophrenia Scores (BACS)
week 4
|
-2.002433521 BACS composite score (z score)
Standard Deviation 1.596431421
|
-1.500292967 BACS composite score (z score)
Standard Deviation 1.477111055
|
Adverse Events
Lurasidone (LUR)
NONLUR
Serious adverse events
| Measure |
Lurasidone (LUR)
n=14 participants at risk
Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks
Compare lurasidone (LUR) group to haloperidol and perphenazine (NONLUR) group
|
NONLUR
n=8 participants at risk
Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.
OR Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.
Compare haloperidol and perphenazine (NONLUR) group to lurasidone (LUR) group.
|
|---|---|---|
|
Endocrine disorders
diabetes mellitus
|
7.1%
1/14 • Number of events 1
|
0.00%
0/8
|
Other adverse events
| Measure |
Lurasidone (LUR)
n=14 participants at risk
Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks
Compare lurasidone (LUR) group to haloperidol and perphenazine (NONLUR) group
|
NONLUR
n=8 participants at risk
Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.
OR Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.
Compare haloperidol and perphenazine (NONLUR) group to lurasidone (LUR) group.
|
|---|---|---|
|
Psychiatric disorders
Sedation
|
21.4%
3/14 • Number of events 3
|
50.0%
4/8 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/14
|
25.0%
2/8 • Number of events 2
|
|
General disorders
Insomnia
|
21.4%
3/14 • Number of events 3
|
0.00%
0/8
|
|
General disorders
Restlessness
|
0.00%
0/14
|
37.5%
3/8 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Stiffness in jaw
|
14.3%
2/14 • Number of events 2
|
0.00%
0/8
|
|
General disorders
Dry mouth
|
0.00%
0/14
|
25.0%
2/8 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place