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Trial record 13 of 2441 for:    NMDA

N-acetylcysteine and NMDA Antagonist Interactions

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00611897
Recruitment Status : Completed
First Posted : February 11, 2008
Results First Posted : May 8, 2015
Last Update Posted : May 8, 2015
Sponsor:
Information provided by (Responsible Party):
Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor)
Condition Cognitive Dysfunction
Interventions Drug: N-acetylcysteine and ketamine
Drug: placebo and ketamine
Enrollment 16
Recruitment Details

The study was approved by the institutional review boards of Yale Medical School and the Veterans Administration Connecticut Healthcare System. Healthy volunteers were recruited by advertisements.

as determined by Structured Clinical Interview for DSM-IV, Non-Patient Edition.

Pre-assignment Details All subjects gave written informed consent. They had no personal or family history of psychiatric or substance abuse disorders. A total of 43 subjects consented; 21 of them never initiated the study due to ineligibility or scheduling conflicts, and 6 subjects dropped out. Sixteen subjects completed the study procedures.
Arm/Group Title Day 1: Active NAC; Day 2: Placebo NAC Day 1: Placebo NAC; Day 2: Active NAC
Hide Arm/Group Description Subjects were randomized to receive ACTIVE NAC on day one, before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Subjects then received PLACEBO NAC on day two, before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Subjects were randomized to receive PLACEBO NAC on day one, before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Subjects then received ACTIVE NAC on day two, before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order.
Period Title: Day 1: Initial Treatment
Started 8 8
Completed 8 8
Not Completed 0 0
Period Title: Day 2: Crossover Treatment
Started 8 8
Completed 8 8
Not Completed 0 0
Arm/Group Title Overall Sample
Hide Arm/Group Description This is the group of healthy volunteers that consented to participate in the study.
Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
27.0  (5.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
3
  18.8%
Male
13
  81.3%
1.Primary Outcome
Title Target P300
Hide Description

The Target P300 measures were obtained from the Fz, Cz and Pz electrodes.

Target stimuli were 1000 Hz tones (500 ms) and novel stimuli (~250 ms) were unique environmental sounds (e.g., dog bark) used in prior studies of the novelty P300. Subjects were instructed to respond to the target sounds by pressing a button using their dominant hand index finger. The standard stimuli were 20, 30 or 40 Hz click trains (500 ms) in the first, second, and third runs, respectively. The auditory steady state EEG driving data obtained from these standard stimuli will be presented in a separate report. All stimuli were presented at 80 dB SPL.

Time Frame daily
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Placebo+Saline Placebo+Ketamine NAC+Saline NAC+Ketamine
Hide Arm/Group Description:
NAC placebo capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC placebo capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
NAC active capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC active capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
Overall Number of Participants Analyzed 16 16 16 16
Least Squares Mean (Standard Error)
Unit of Measure: microvolts
Fz 2.5  (0.8) 3.2  (0.8) 5.2  (0.8) 3.4  (0.8)
Cz 7.7  (1.0) 5.5  (1.0) 9.9  (1.0) 5.4  (1.0)
Pz 11.8  (1.1) 8.1  (1.1) 12.6  (1.1) 8.2  (1.1)
2.Primary Outcome
Title Novel P300
Hide Description

The Novel P300 measures were obtained from the Fz, Cz and Pz electrodes.

Target stimuli were 1000 Hz tones (500 ms) and novel stimuli (~250 ms) were unique environmental sounds (e.g., dog bark) used in prior studies of the novelty P300. Subjects were instructed to respond to the target sounds by pressing a button using their dominant hand index finger. The standard stimuli were 20, 30 or 40 Hz click trains (500 ms) in the first, second, and third runs, respectively. The auditory steady state EEG driving data obtained from these standard stimuli will be presented in a separate report. All stimuli were presented at 80 dB SPL.

Time Frame daily
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Placebo+Saline Placebo+Ketamine NAC+Saline NAC+Ketamine
Hide Arm/Group Description:
NAC placebo capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC placebo capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
NAC active capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC active capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
Overall Number of Participants Analyzed 16 16 16 16
Least Squares Mean (Standard Error)
Unit of Measure: microvolts
Fz 5.6  (0.8) 5.2  (0.8) 7.6  (0.8) 5.3  (0.8)
Cz 10.5  (1.0) 7.0  (1.0) 11.5  (1.0) 7.4  (1.0)
Pz 10.7  (1.2) 5.7  (1.2) 10.8  (1.2) 6.1  (1.2)
3.Secondary Outcome
Title Mismatch Negativity (MMN) Intensity
Hide Description

Mismatch Negativity (MMN) Intensity difference waves at midline electrodes (Fz, Cz and Pz).

The frequent standard tones were of 75 ms duration with 5 ms rise and fall time, and were composed of 500, 1000, and 1500 Hz sinusoidal partials (harmonics) that resulted in a single high pitched beep sound.

All tones were presented at 76 dB sound pressure level (SPL) with the exception of intensity deviants. The three deviants were distinguishable from standard tones in either intensity, frequency, or duration.

Subjects performed a visual discrimination distractor task during the MMN runs and were instructed to ignore the tones.

The mismatch negativity (MMN) measure included 3 types of deviant tones (stimuli) that the subjects heard: 1. Frequency deviant, 2. Intensity deviant, 3. Duration deviant. The response to these 3 types of deviants were recorded in the EEG. Therefore each deviant was associated with different waves which we measured in amplitude (microvolts)

Time Frame daily
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Placebo+Saline Placebo+Ketamine NAC+Saline NAC+Ketamine
Hide Arm/Group Description:
NAC placebo capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC placebo capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
NAC active capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC active capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
Overall Number of Participants Analyzed 16 16 16 16
Least Squares Mean (Standard Error)
Unit of Measure: microvolts
Fz -3.5  (0.2) -2.7  (0.2) -3.4  (0.2) -2.6  (0.2)
Cz -3.2  (0.2) -2.5  (0.2) -3.4  (0.2) -2.6  (0.2)
Pz -2.1  (0.2) -2.0  (0.2) -2.4  (0.2) -2.1  (0.2)
4.Secondary Outcome
Title Mismatch Negativity (MMN) Frequency
Hide Description

Mismatch Negativity (MMN) Frequency difference waves at midline electrodes (Fx, Cz and Pz).

The frequent standard tones were of 75 ms duration with 5 ms rise and fall time, and were composed of 500, 1000, and 1500 Hz sinusoidal partials (harmonics) that resulted in a single high pitched beep sound.

All tones were presented at 76 dB sound pressure level (SPL) with the exception of intensity deviants. The three deviants were distinguishable from standard tones in either intensity, frequency, or duration.

Subjects performed a visual discrimination distractor task during the MMN runs and were instructed to ignore the tones.

The mismatch negativity (MMN) measure included 3 types of deviant tones (stimuli) that the subjects heard: 1. Frequency deviant, 2. Intensity deviant, 3. Duration deviant. The response to these 3 types of deviants were recorded in the EEG. Therefore each deviant was associated with different waves which we measured in amplitude (microvolts)

Time Frame daily
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Placebo+Saline Placebo+Ketamine NAC+Saline NAC+Ketamine
Hide Arm/Group Description:
NAC placebo capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC placebo capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
NAC active capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC active capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
Overall Number of Participants Analyzed 16 16 16 16
Least Squares Mean (Standard Error)
Unit of Measure: microvolts
Fz -3.3  (0.3) -2.7  (0.3) -3.1  (0.2) -2.9  (0.2)
Cz -3.3  (0.3) -2.7  (0.3) -3.1  (0.2) -2.9  (0.2)
Pz -2.3  (0.2) -1.7  (0.2) -1.8  (0.2) -1.9  (0.2)
5.Secondary Outcome
Title Mismatch Negativity (MMN) Duration
Hide Description

Mismatch Negativity (MMN) Duration difference waves at midline electrodes (Fz, Cz and Pz).

The frequent standard tones were of 75 ms duration with 5 ms rise and fall time, and were composed of 500, 1000, and 1500 Hz sinusoidal partials (harmonics) that resulted in a single high pitched beep sound.

All tones were presented at 76 dB sound pressure level (SPL) with the exception of intensity deviants. The three deviants were distinguishable from standard tones in either intensity, frequency, or duration.

Subjects performed a visual discrimination distractor task during the MMN runs and were instructed to ignore the tones.

The mismatch negativity (MMN) measure included 3 types of deviant tones (stimuli) that the subjects heard: 1. Frequency deviant, 2. Intensity deviant, 3. Duration deviant. The response to these 3 types of deviants were recorded in the EEG. Therefore each deviant was associated with different waves which we measured in amplitude (microvolts)

Time Frame daily
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol
Arm/Group Title Placebo+Saline Placebo+Ketamine NAC+Saline NAC+Ketamine
Hide Arm/Group Description:
NAC placebo capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC placebo capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
NAC active capsule administered after receiving 1-min bolus of saline, followed by a 70-min long saline infusion during which behavioral, cognitive, and ERP data were collected.
NAC active capsule, Ketamine was administered intravenously as a bolus of .29 mg/kg for 40 min.
Overall Number of Participants Analyzed 16 16 16 16
Least Squares Mean (Standard Error)
Unit of Measure: microvolts
Fz -3.2  (0.3) -3.1  (0.3) -3.2  (0.3) -2.8  (0.3)
Cz -3.1  (0.3) -3.1  (0.3) -3.3  (0.3) -2.8  (0.3)
Pz -2.4  (0.2) -2.3  (0.2) -2.4  (0.2) -2.1  (0.2)
Time Frame Adverse events were collected across the duration of the intervention in both arms. These data were not collected at the specific intervals in either arm.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Day 1: Placebo NAC; Day 2: Active NAC Day 1: Active NAC; Day 2: Placebo NAC
Hide Arm/Group Description Subjects were randomized to receive PLACEBO NAC on day one, before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Subjects then received ACTIVE NAC on day two, before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Subjects were randomized to receive ACTIVE NAC on day one, before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Subjects then received PLACEBO NAC on day two, before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order.
All-Cause Mortality
Day 1: Placebo NAC; Day 2: Active NAC Day 1: Active NAC; Day 2: Placebo NAC
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Day 1: Placebo NAC; Day 2: Active NAC Day 1: Active NAC; Day 2: Placebo NAC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/8 (0.00%)      0/8 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Day 1: Placebo NAC; Day 2: Active NAC Day 1: Active NAC; Day 2: Placebo NAC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/8 (50.00%)      0/8 (0.00%)    
Gastrointestinal disorders     
Nausea   4/8 (50.00%)  4 0/8 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Handan Gunduz-Bruce, MD
Organization: Yale School of Medicine, Department of Psychiatry
Phone: (203) 785-2117
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00611897     History of Changes
Other Study ID Numbers: 0508000518
First Submitted: January 29, 2008
First Posted: February 11, 2008
Results First Submitted: January 10, 2013
Results First Posted: May 8, 2015
Last Update Posted: May 8, 2015