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

• Sponsor: Herzog Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02051426
• Collaborator: (none)
• Enrollment: 35
• Arms: 2
• Duration (Months): 69.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy	Other: D-serine; Other: Placebo	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Official Title: Behavioral and Cognitive Effects of the N-methyl-D-aspartate Receptor (NMDAR) Co-agonist D-serine in Healthy Humans
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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] ).

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• healthy volunteers

Exclusion Criteria:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Herzog Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Herzog Hospital
• ClinicalTrials.gov Identifier: NCT02051426
• Other Study ID Numbers: 112-06
• First Posted: Jan 31, 2014
• Last Update Posted: Nov 19, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by Herzog Hospital: neuropsychiatric effects

Study Results

Participant Flow

Arm/Group Title	D-serine First, Then Placebo	Placebo First, Then D-serine
Arm/Group Description	D-serine (2.1g), then Placebo (corn starch)	corn starch, then D-serine (2.1g)
Period Title: First Intervention
STARTED	16	19
COMPLETED	16	19
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	16	19
COMPLETED	16	19
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	16	19
COMPLETED	16	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	D-serine First, Then Placebo	Placebo First, Then D-serine	Total
Arm/Group Description	D-serine (2.1g), then placebo (corn starch)	corn starch, then D-serine (2.1g)	Total of all reporting groups
Overall Participants	16	19	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.58 (3.0)	26.58 (3.0)	26.58 (3.0)
Sex/Gender, Customized (participants) [Number]
female	5 31.3%	8 42.1%	13 37.1%
male	11 68.8%	11 57.9%	22 62.9%

Outcome Measures

1. Primary Outcome

Title	Change in Visual Analogue Scale (VAS) of Anxiety - From Baseline to 2 Hours
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	D-serine	Placebo
Arm/Group Description	D-serine (2.1g)	corn starch
Measure Participants	35	35
Mean (Standard Deviation) [units on a scale]	0.5 (0.2)	0.0 (0.2)

2. Primary Outcome

Title	Change in Cognitive Function- CPT-IP D-prime Score - From Baseline to 2 Hours
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	D-serine	Placebo
Arm/Group Description	D-serine (2.1g)	corn starch
Measure Participants	35	35
Mean (Standard Deviation) [units on a scale]	.5 (.2)	0 (.2)

3. Primary Outcome

Title	Change in Rey Auditory Verbal Learning Test RAVLT (Trial 7) - From Baseline to 2 Hours
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	D-serine	Placebo
Arm/Group Description	D-serine (2.1g)	corn starch
Measure Participants	35	35
Mean (Standard Deviation) [units on a scale]	2 (.3)	.3 (.3)

Adverse Events

Time Frame	at the end of test days 1 and 2
Adverse Event Reporting Description	Udvalg for Kliniske Undersogelser (UKU) Side Effects Rating Scale
Arm/Group Title	D-serine		Placebo
Arm/Group Description	D-serine (2.1g)		corn starch
All Cause Mortality
	D-serine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	D-serine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	D-serine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.