Behavioral and Cognitive Effects of the N-methyl-D-aspartate Receptor (NMDAR) Co-agonist D-serine in Healthy Humans

Study Overview
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Brief Summary
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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
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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.

Official Title
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Behavioral and Cognitive Effects of the N-methyl-D-aspartate Receptor (NMDAR) Co-agonist D-serine in Healthy Humans

Conditions
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Healthy

Intervention / Treatment
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* Other: D-serine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy volunteers Exclusion Criteria: history of psychiatric, medical, neurological illness or substance abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D-serine<br>single P.O. administration of D-serine (2.1g) | Other: D-serine<br>* single P.O. administration of D-serine (2.1g)<br>* Other names: DSR;|
| Placebo Comparator: Placebo<br>single P.O. administration of corn starch | Other: Placebo<br>* single P.O. administration of Placebo<br>* Other names: corn starch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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] ). | Baseline, 2 hours post intervention | 
| 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. | Baseline, 2 hours post intervention | 
| 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. | Baseline, 2 hours post intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuropsychiatric effects