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

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: D-serine; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy volunteers

Exclusion Criteria:

• history of psychiatric, medical, neurological illness or substance abuse

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Herzog Hospital
• Investigators: Principal Investigator: Uriel Heresco-Levy, M.D., Herzog Hospital

Publications and helpful links

General Publications

• Levin R, Dor-Abarbanel AE, Edelman S, Durrant AR, Hashimoto K, Javitt DC, Heresco-Levy U. Behavioral and cognitive effects of the N-methyl-D-aspartate receptor co-agonist D-serine in healthy humans: initial findings. J Psychiatr Res. 2015 Feb;61:188-95. doi: 10.1016/j.jpsychires.2014.12.007. Epub 2014 Dec 24.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: January 27, 2014
• First Submitted That Met QC Criteria: January 30, 2014
• First Posted (Estimate): January 31, 2014

Study Record Updates

• Last Update Posted (Estimate): November 19, 2014
• Last Update Submitted That Met QC Criteria: November 12, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: neuropsychiatric effects
• Other Study ID Numbers: 112-06