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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

Tracking Information
First Submitted Date  ICMJE January 29, 2008
First Posted Date  ICMJE February 11, 2008
Results First Submitted Date  ICMJE January 10, 2013
Results First Posted Date  ICMJE May 8, 2015
Last Update Posted Date May 8, 2015
Study Start Date  ICMJE January 2006
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2015)
  • Target P300 [ Time Frame: daily ]
    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.
  • Novel P300 [ Time Frame: daily ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 29, 2008)
P300 as detected by ERP [ Time Frame: prospective ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2015)
  • Mismatch Negativity (MMN) Intensity [ Time Frame: daily ]
    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)
  • Mismatch Negativity (MMN) Frequency [ Time Frame: daily ]
    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)
  • Mismatch Negativity (MMN) Duration [ Time Frame: daily ]
    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)
Original Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2008)
MMN [ Time Frame: prospective ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE N-acetylcysteine and NMDA Antagonist Interactions
Official Title  ICMJE N-acetylcysteine and NMDA Antagonist Interactions
Brief Summary This study tests the hypothesis that extrasynaptic mechanisms are critically linked with cognitive effects of NMDA antagonism as evidenced by event-related potentials (ERPs) in healthy humans.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Condition  ICMJE Cognitive Dysfunction
Intervention  ICMJE
  • Drug: N-acetylcysteine and ketamine
    Active drug (N-acetylcysteine)
    Other Name: NAC
  • Drug: placebo and ketamine
    placebo N-acetylcysteine
Study Arms  ICMJE
  • Active Comparator: Arm I
    The NAC capsules were administered orally in divided doses: 2000 mg followed by 1000 mg 2 hours later. Each morning, 165 min after NAC administration, subjects received a 1-min bolus of normal saline, followed by a 70-minlong saline infusion during which behavioral, cognitive, and ERP data were collected. Ketamine was administered intravenously as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min (SPM and RVP), and then .29 mg/kg for 40 min (P300 and MMN).
    Intervention: Drug: N-acetylcysteine and ketamine
  • Placebo Comparator: Arm II
    The placebo capsules were administered orally in divided doses: 2000 mg followed by 1000 mg 2 hours later. Each morning, 165 min after placebo administration, subjects received a 1-min bolus of normal saline, followed by a 70-minlong saline infusion during which behavioral, cognitive, and ERP data were collected. Ketamine was administered intravenously as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min (SPM and RVP), and then .29 mg/kg for 40 min (P300 and MMN).
    Intervention: Drug: placebo and ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 17, 2012)
16
Original Estimated Enrollment  ICMJE
 (submitted: January 29, 2008)
20
Actual Study Completion Date  ICMJE February 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ages of 21-45 years from all ethnic backgrounds.
  • Male or female.
  • Written informed consent.

Exclusion criteria

  • DSM-IV diagnosis for a psychotic, depressive or anxiety disorder.
  • A history of significant medical/neurological disease such as cardiac, thyroid, renal, hepatic abnormality, seizure disorder. Unstable medical condition based on EKG, vital signs, physical examination and laboratory work-up (CBC with differential, SMA-7, LFTs, TFTs, UA, Utox, Urine pregnancy test) .
  • History of severe allergies or multiple adverse drug reactions.
  • Any medication that in the opinion of the PI could interfere with either the safety of the study and/or the outcome measures.
  • Any other conditions which in the opinion of the investigator would preclude participation in the study.
  • History of major psychiatric disorder in first degree relatives.
  • Current substance abuse/dependency determined by urine toxicology.
  • Current treatment with medications with psychotropic effects.
  • Treatment with benzodiazepines within one week prior to testing.
  • Current pregnancy, unsatisfactory birth control method report for females.
  • Education < 10th grade.
  • IQ < 70, MR as determined by Wechsler Abbreviated Scale of Intelligence.
  • Non-English speaking.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00611897
Other Study ID Numbers  ICMJE 0508000518
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Handan Gunduz-Bruce, M.D. Yale School of Medicine
PRS Account Yale University
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP