Healthy
Conditions
Keywords
neuropsychiatric effects
Brief summary
The efficacy of compounds having agonistic activity at the glycine site associated with the N-methyl-D-aspartate receptor (NMDAR) is presently assessed in psychiatric disorders. In contrast to NMDAR antagonists, the neuropsychiatric effects of NMDAR agonists in the healthy human organism are not known. The investigators studied neuropsychiatric and neurochemical effects of the NMDAR-glycine site obligatory co-agonist D-serine (DSR) in healthy subjects using a randomized, controlled crossover challenge design including a baseline assessment day and two treatment administration days (DSR and placebo in randomized order). Thirty-five subjects aged 23-29 years participated in the study and received a 2.1g orally administered DSR dose. The main outcome measures were the changes in scores of mood-related Visual Analogue Scale (VAS), Continuous Performance Test - Identical Pairs (CPT-IP), and Rey Auditory Verbal Learning Test (RAVLT).
Detailed description
The study employed a randomized, double-blind, placebo controlled crossover design according to which, following a baseline assessment session, subjects were tested under two acute treatment conditions on two separate days. Following the baseline assessment day, 16 subjects were randomized, using a computer-generated random number sequence, to receive during test day 1 DSR and 19 to receive placebo. During test day 2, these two groups of subjects were crossed over to receive the alternative experimental treatment. The time intervals between the baseline assessment day, test day 1 and test day 2 were two to three weeks and 1 month respectively, in order to avoid the possibility of any carry-over effects.
Interventions
OTHERD-serine
single P.O. administration of D-serine (2.1g)
OTHERPlacebo
single P.O. administration of Placebo
Sponsors
Herzog Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy volunteers
Exclusion criteria
* history of psychiatric, medical, neurological illness or substance abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analogue Scale (VAS) of Anxiety - From Baseline to 2 Hours | Baseline, 2 hours post intervention | The subject was asked to point on the VAS scale according to his anxiety level. VAS anxiety scale 0 to 10 ( 0 \[no anxiety\] to 10 \[maximum anxiety\] ). |
| Change in Cognitive Function- CPT-IP D-prime Score - From Baseline to 2 Hours | Baseline, 2 hours post intervention | The d-prime score is a score given to each participant on a scale of 0.0 - 1.0 in which discrimination sensitivity is measured. A score of 0 equates to no sensitivity whereas a score of 1.0 equates to perfect sensitivity. |
| Change in Rey Auditory Verbal Learning Test RAVLT (Trial 7) - From Baseline to 2 Hours | Baseline, 2 hours post intervention | RAVLT measures short term verbal memory, verbal learning, susceptibility to (proactive and retroactive) interference, retention of information after a certain period of time during which other activities are performed and recognition memory. The test consists of a list of 15 common nouns, which are read to the subject in five consecutive trials (trials 1 through 5); each reading is followed by a free-recall task. In trial 6, an interface list of 15 new common nouns is presented, followed by free recall of these new nouns. In trial 7, without additional reading, subjects are again asked to recall the first list. Twenty minutes later, without an additional reading, subjects are asked to recall once more the first list (trial 8). The RAVLT score range from 0-90 correctly recalled words. For trial 7 the score ranges from 0 to 15 correctly recalled words. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D-serine First, Then Placebo D-serine (2.1g), then placebo (corn starch) | 16 |
| Placebo First, Then D-serine corn starch, then D-serine (2.1g) | 19 |
| Total | 35 |
Baseline characteristics
| Characteristic | D-serine First, Then Placebo | Placebo First, Then D-serine | Total |
|---|---|---|---|
| Age, Continuous | 26.58 years STANDARD_DEVIATION 3 | 26.58 years STANDARD_DEVIATION 3 | 26.58 years STANDARD_DEVIATION 3 |
| Sex/Gender, Customized female | 5 participants | 8 participants | 13 participants |
| Sex/Gender, Customized male | 11 participants | 11 participants | 22 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
Change in Cognitive Function- CPT-IP D-prime Score - From Baseline to 2 Hours
The d-prime score is a score given to each participant on a scale of 0.0 - 1.0 in which discrimination sensitivity is measured. A score of 0 equates to no sensitivity whereas a score of 1.0 equates to perfect sensitivity.
Time frame: Baseline, 2 hours post intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine | Change in Cognitive Function- CPT-IP D-prime Score - From Baseline to 2 Hours | .5 units on a scale | Standard Deviation 0.2 |
| Placebo | Change in Cognitive Function- CPT-IP D-prime Score - From Baseline to 2 Hours | 0 units on a scale | Standard Deviation 0.2 |
Primary
Change in Rey Auditory Verbal Learning Test RAVLT (Trial 7) - From Baseline to 2 Hours
RAVLT measures short term verbal memory, verbal learning, susceptibility to (proactive and retroactive) interference, retention of information after a certain period of time during which other activities are performed and recognition memory. The test consists of a list of 15 common nouns, which are read to the subject in five consecutive trials (trials 1 through 5); each reading is followed by a free-recall task. In trial 6, an interface list of 15 new common nouns is presented, followed by free recall of these new nouns. In trial 7, without additional reading, subjects are again asked to recall the first list. Twenty minutes later, without an additional reading, subjects are asked to recall once more the first list (trial 8). The RAVLT score range from 0-90 correctly recalled words. For trial 7 the score ranges from 0 to 15 correctly recalled words.
Time frame: Baseline, 2 hours post intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine | Change in Rey Auditory Verbal Learning Test RAVLT (Trial 7) - From Baseline to 2 Hours | 2 units on a scale | Standard Deviation 0.3 |
| Placebo | Change in Rey Auditory Verbal Learning Test RAVLT (Trial 7) - From Baseline to 2 Hours | .3 units on a scale | Standard Deviation 0.3 |
Primary
Change in Visual Analogue Scale (VAS) of Anxiety - From Baseline to 2 Hours
The subject was asked to point on the VAS scale according to his anxiety level. VAS anxiety scale 0 to 10 ( 0 \[no anxiety\] to 10 \[maximum anxiety\] ).
Time frame: Baseline, 2 hours post intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-serine | Change in Visual Analogue Scale (VAS) of Anxiety - From Baseline to 2 Hours | 0.5 units on a scale | Standard Deviation 0.2 |
| Placebo | Change in Visual Analogue Scale (VAS) of Anxiety - From Baseline to 2 Hours | 0.0 units on a scale | Standard Deviation 0.2 |