N-acetylcysteine and NMDA Antagonist Interactions

Cognitive Dysfunction Clinical Trial

Official title:

N-acetylcysteine and NMDA Antagonist Interactions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00611897
• Other study ID #: 0508000518
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 29, 2008
• Last updated: May 7, 2015
• Start date: January 2006
• Est. completion date: February 2011

Study information

• Verified date: May 2015
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 45 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Dysfunction

Intervention

Drug:
• N-acetylcysteine and ketamine
Active drug (N-acetylcysteine)
• placebo and ketamine
placebo N-acetylcysteine

Locations

Country	Name	City	State
United States	VHA Connecticut	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Target P300	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.	daily	No
Primary	Novel P300	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.	daily	No
Secondary	Mismatch Negativity (MMN) Intensity	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)	daily	No
Secondary	Mismatch Negativity (MMN) Frequency	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)	daily	No
Secondary	Mismatch Negativity (MMN) Duration	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)	daily	No