Cognitive DysfunctionPhase 1/2NCT00611897

N-acetylcysteine and NMDA Antagonist Interactions

A Phase 1/2 study testing N-acetylcysteine and ketamine in people with Cognitive Dysfunction, run by Yale University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 21 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Cognitive Dysfunction
What is being tested?: N-acetylcysteine and ketamine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 16 participants
Where: 1 siteUnited States
Study dates: Jan 2006to Feb 2011
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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.

Show all 13Show fewer

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 locations and contacts

1 site in 1 country.

United States1 site

VHA Connecticut
West Haven, Connecticut, 06516

Other trials in United States

About this study

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
Being tested: N-acetylcysteine and ketamine, placebo and ketamine
Keywords: NMDA, glutamate, N-acetylcysteine, P3
Medical subject headings: Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

N-acetylcysteine and ketamineDrug
Also called NAC
Active drug (N-acetylcysteine)
placebo and ketamineDrug
placebo N-acetylcysteine

Study groups in NCT00611897
Study group	Role	What they receive
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). Receives: 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). Receives: Drug: placebo and ketamine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: daily

Secondary outcomes (3)

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)
Measured: daily
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)
Measured: daily
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)
Measured: daily

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2006Feb 2011

First posted11 Feb 2008 (estimated)
Study startJan 2006
Primary completionFeb 2011
Study completionFeb 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Cognitive DysfunctionStudies of the same condition, open and under way.
More trials run by Yale UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00611897
Sponsor's protocol ID: 0508000518
Status last verified: May 2015
First submitted: 29 Jan 2008
Last updated: 8 May 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Cognitive Dysfunction trials

Study at a glance

From the registry record, last updated by the sponsor on 8 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: N-acetylcysteine and NMDA Antagonist Interactions
ClinicalTrials.gov ID: NCT00611897
Acronym / sponsor ID: 0508000518
Conditions: Cognitive Dysfunction
Keywords: NMDA, glutamate, N-acetylcysteine, P3
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Study start: Jan 2006
Primary completion: Feb 2011 (actual)
Study completion: Feb 2011 (actual)
First posted: 11 Feb 2008 (estimated)
Results: Posted 8 May 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Arm I	Active comparator	Drug: N-acetylcysteine and ketamineThe 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).
Arm II	Placebo comparator	Drug: placebo and ketamineThe 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).

Who may qualify

Ages: 21 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (13 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
N-acetylcysteine and ketamineAlso: NACActive drug (N-acetylcysteine)	Drug	Arm I
placebo and ketamineplacebo N-acetylcysteine	Drug	Arm II

Primary outcome

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.

3 secondary outcomes

Mismatch Negativity (MMN) Intensity
Time frame: daily
Mismatch Negativity (MMN) Frequency
Time frame: daily
Mismatch Negativity (MMN) Duration
Time frame: daily

Results and safety

Results posted to the registry on 8 May 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Day 1: Active NAC; Day 2: Placebo NAC	8	8
Day 1: Placebo NAC; Day 2: Active NAC	8	8

Primary outcome: Target P300

Time frame: daily. Least squares mean (Standard Error). Unit: microvolts

Measure	Placebo+Saline n = 16	Placebo+Ketamine n = 16	NAC+Saline n = 16	NAC+Ketamine n = 16
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)

Population analysed: Per protocol

Primary outcome: Novel P300

Time frame: daily. Least squares mean (Standard Error). Unit: microvolts

Measure	Placebo+Saline n = 16	Placebo+Ketamine n = 16	NAC+Saline n = 16	NAC+Ketamine n = 16
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)

Population analysed: Per protocol

3 secondary outcomes are reported in the full results.

Adverse events

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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Day 1: Placebo NAC; Day 2: Active NAC	0 of 8 (0%)	4 of 8 (50%)	Not reported
Day 1: Active NAC; Day 2: Placebo NAC	0 of 8 (0%)	0 of 8 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Handan Gunduz-Bruce, M.D. principal investigator

Yale University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing N-acetylcysteine and ketamine in people with Cognitive Dysfunction, run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Target P300 (time frame: daily). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00611897.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2015.