N-acetylcysteine and NMDA Antagonist Interactions

NCT00611897 | Completed Phase 1 Results

• 1 other identifier: 0508000518
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Dysfunction

Keywords

NMDA; glutamate; N-acetylcysteine; P3

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (3)

• Mismatch Negativity (MMN) Intensity

  daily

• Mismatch Negativity (MMN) Frequency

  daily

• Mismatch Negativity (MMN) Duration

  daily

Study Arms (2)

Arm I

ACTIVE COMPARATOR

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).

Drug: N-acetylcysteine and ketamine

Arm II

PLACEBO COMPARATOR

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).

Drug: placebo and ketamine

Interventions

N-acetylcysteine and ketamine DRUG

Active drug (N-acetylcysteine)

Also known as: NAC

Arm I

placebo and ketamine DRUG

placebo N-acetylcysteine

Arm II

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

VHA Connecticut

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Acetylcysteine; Ketamine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Handan Gunduz-Bruce, MD
• Organization: Yale School of Medicine, Department of Psychiatry

handan.gunduz-bruce@yale.edu

(203) 785-2117

Study Officials

• Handan Gunduz-Bruce, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 11, 2008
• Study Start: January 1, 2006
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: May 8, 2015
• Results First Posted: May 8, 2015

Record last verified: 2015-05

Locations

US (1)