Trial Outcomes & Findings for D-serine Augmentation of Neuroplasticity (NCT NCT03711500)
NCT ID: NCT03711500
Last Updated: 2022-06-14
Results Overview
Participants underwent three treatment sessions, 1x week. This is the outcome of the auditory remediation. In Auditory Remediation, participants are presented with paired tones (e.g. Stimulus 1 ("reference") and Stimulus 2 ("test"): S1 and S2) and indicate which tone is higher in pitch (frequency). In the first pair, the ratio is 50% (e.g. 1000±500 Hz). A two-down/one-up staircase procedure is used to adjust the ratio to maintain a steady (\~70% correct) level of performance across the trial. The tone matching threshold was calculated at the initial plateau (trials 20-30 during treatment session 1) and at the end of treatment session three. Plasticity Improvement was operationalized as change in threshold from initial plateau to the end of treatment visit 3. Larger (more positive) values represent greater improvement in threshold. Zero would represent no improvement. Values were log transformed.
COMPLETED
PHASE1/PHASE2
45 participants
At the end of Treatment session 3 (3rd of three sessions)
2022-06-14
Participant Flow
Participant milestones
| Measure |
D-serine 80 mg/kg
D-serine 80 m/kg
|
D-serine 100 mg/kg
D-serine 100 mg/kg
|
D-serine 120 mg/kg
D-serine 120 mg/kg
|
Placebo
Placebo
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
12
|
12
|
12
|
9
|
|
Overall Study
COMPLETED
|
12
|
11
|
12
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
D-serine Augmentation of Neuroplasticity
Baseline characteristics by cohort
| Measure |
D-serine 80 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
Placebo
n=9 Participants
Placebo: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 100 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 120 mg/g
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
34.8 years
STANDARD_DEVIATION 9.6 • n=99 Participants
|
34.8 years
STANDARD_DEVIATION 8 • n=107 Participants
|
37.6 years
STANDARD_DEVIATION 6.6 • n=206 Participants
|
35.9 years
STANDARD_DEVIATION 8.4 • n=7 Participants
|
35.9 years
STANDARD_DEVIATION 8 • n=31 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
9 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
36 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
21 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
24 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Region of Enrollment
United States
|
12 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
45 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: At the end of Treatment session 3 (3rd of three sessions)Population: randomized
Participants underwent three treatment sessions, 1x week. This is the outcome of the auditory remediation. In Auditory Remediation, participants are presented with paired tones (e.g. Stimulus 1 ("reference") and Stimulus 2 ("test"): S1 and S2) and indicate which tone is higher in pitch (frequency). In the first pair, the ratio is 50% (e.g. 1000±500 Hz). A two-down/one-up staircase procedure is used to adjust the ratio to maintain a steady (\~70% correct) level of performance across the trial. The tone matching threshold was calculated at the initial plateau (trials 20-30 during treatment session 1) and at the end of treatment session three. Plasticity Improvement was operationalized as change in threshold from initial plateau to the end of treatment visit 3. Larger (more positive) values represent greater improvement in threshold. Zero would represent no improvement. Values were log transformed.
Outcome measures
| Measure |
D-serine 80 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
Placebo
n=9 Participants
Placebo: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 100 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 120 mg/g
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
|---|---|---|---|---|
|
Plasticity Improvement (Change in Tone Matching Threshold)
|
13.9 log ratio
Standard Deviation 17.5
|
5.3 log ratio
Standard Deviation 10.8
|
11 log ratio
Standard Deviation 16.4
|
-0.05 log ratio
Standard Deviation 14.1
|
PRIMARY outcome
Timeframe: Post baselinePopulation: randomized
MMN is measured by electroencephalogram (EEG). MMN will be obtained independently to pitch stimuli utilizing the same base frequency as the plasticity task described in outcome 1. MMN was assessed immediately before the first dose and immediately after treatment sessions 2 and 3. MMN will be generated using previously published methods. Peak amplitude at frontocentral electrodes within predefined latency range will be primary outcome measure. This value represents the mean MMN to pitch post baseline (after sessions 2 and 3). More negative represents larger MMN.
Outcome measures
| Measure |
D-serine 80 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
Placebo
n=9 Participants
Placebo: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 100 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 120 mg/g
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
|---|---|---|---|---|
|
Mismatch Negativity (MMN)
|
-1.83 amplitude, micro volts
Standard Deviation 2.1
|
-1.05 amplitude, micro volts
Standard Deviation 1.6
|
-2.71 amplitude, micro volts
Standard Deviation 1.7
|
-0.56 amplitude, micro volts
Standard Deviation 1.5
|
PRIMARY outcome
Timeframe: Week 1Population: randomized
Theta is measured by EEG, during the motor-preparation interval (200-500 ms post-the second tone: S2) during the auditory remediation task. Theta inter-trial coherence (ITC) reflects the consistency of spectral response across repeated trials ranging from 0 (no consistency) to 1 (perfect consistency). Higher values represent better consistency.
Outcome measures
| Measure |
D-serine 80 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
Placebo
n=9 Participants
Placebo: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 100 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 120 mg/g
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
|---|---|---|---|---|
|
Theta Intertrial Coherence (Theta)
|
.229 correlation coefficient (r)
Standard Deviation .06
|
.241 correlation coefficient (r)
Standard Deviation .06
|
0.274 correlation coefficient (r)
Standard Deviation .06
|
.241 correlation coefficient (r)
Standard Deviation .07
|
PRIMARY outcome
Timeframe: Three weeksThis is a safety measure conducted by urinalysis after each D-serine dose. The outcome is the count of participants with granular casts.
Outcome measures
| Measure |
D-serine 80 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
Placebo
n=9 Participants
Placebo: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 100 mg/kg
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
D-serine 120 mg/g
n=12 Participants
D-serine: Subjects will receive three sessions of auditory remediation paired with either D-serine or Placebo in a 4:1 D-serine:placebo ratio. This will be conducted in 3 separate cohorts of D-serine dose 80, 100 and 120 mg/kg, which 15 subjects per cohort (12 active and 3 placebo) per cohort
|
|---|---|---|---|---|
|
Number of Patients With Granular Casts
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
D-serine 80 mg/kg
Placebo
D-serine 100 mg/kg
D-serine 120 mg/g
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Joshua Kantrowitz
New York State Psychiatric Institute
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place