N-acetylcysteine and NMDA Antagonist Interactions

Yale University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Cognitive Dysfunction

Treatments: Drug: placebo and ketamine; Drug: N-acetylcysteine and ketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT00611897

0508000518

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 21 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

16 participants in 2 patient groups, including a placebo group

Arm I

Active Comparator group

Description:

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).

Treatment:

Drug: N-acetylcysteine and ketamine

Arm II

Placebo Comparator group

Description:

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).

Treatment:

Drug: placebo and ketamine