SchizophreniaPhase 2NCT00129441

Gamma-Amino Butyric Acid (GABA)-A Alpha2/3 Study

A Phase 2 study testing Merck L-830982 in people with Schizophrenia, run by University of Pittsburgh 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

The purpose of this research study is to determine whether a short-term administration of an investigational study drug may provide evidence of improvement in cognitive functioning in a group of stable male subjects with schizophrenia. Read more about this study

Who is it for?: Ages 18 to 50 years, men only
Conditions the study is for: Schizophrenia
What is being tested?: Merck L-830982
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 16 participants
Where: 1 siteUnited States
Study dates: Aug 2005to Jan 2008
Phase: Phase 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 18 to 50 years
Men only
No healthy volunteers
Adult

Who may be able to join

Male participants
Between the ages of 18 and 50
Meet diagnostic criteria for schizophrenia or schizoaffective disorder
Are clinically stable for a minimum of 3 months on current dose of medication
Are unemployed (i.e., work less than 20 hours per week at competitive employment)

Who cannot join

Psychoactive substance dependence within the past 6 months or substance abuse within the past month
History of head trauma or other neurological disorder
Medical illness or medications, such as benzodiazepine treatment or HIV medications, that may be affected by study participation (the study doctor will discuss this with potential subjects)
Mental retardation
Seizure disorder
History of a heart attack, arrhythmia, or other heart disease

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Pittsburgh
Pittsburgh, Pennsylvania, 15213

Other trials in United States

About this study

Official title: Treatment of Cognitive Disability in Schizophrenia With a GABA-A Alpha2/3 Receptor Agonist

Read the detailed description

The goal of this study is to determine whether the short-term (4 week), double-blind administration of Merck L-830982 provides evidence of improvement in cognitive functioning in stable male subjects with schizophrenia. This initial, small sample size study (n=9 on L-830982 and n=6 on placebo) is restricted to males in order to reduce the variance that might be attributable to the well-documented sex differences in the clinical features of schizophrenia.

Conditions: Schizophrenia
Being tested: Merck L-830982, Placebo
Keywords: schizophrenia
Medical subject headings: Schizophrenia

What participants receive

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

Merck L-830982Drug
Also called MK-0777
The initial dose of L-830982 was 3.0 mg twice daily (b.i.d.) the dosage increased to 5.0 mg b.i.d. at the end of week 1 and 8.0 mg b.i.d. at the end of week 2, which was continued for the remaining 2 weeks of the trial. Medications were dispensed weekly in blister packs by the hospital pharmacy.
PlaceboDrug
Medications were dispensed weekly in blister packs by the hospital pharmacy, using the same number of pills as those on active drug.

Study groups in NCT00129441
Study group	Role	What they receive
Merck L-830982	Experimental	Not described Receives: Drug: Merck L-830982
Sugar pill	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

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

N-back Task - Reaction Time
The N-back task is a sequential-letter memory task for which working memory load is varied, as the respondent must indicate when the current stimulus matches the one from 'n' steps earlier in the sequence. The dependent measure for the N-back task was performance in the 2-back condition, which provides the best index of performance and dorsolateral prefrontal cortex disturbances in subjects with schizophrenia.
Measured: Week 4
N-back Task - Error Rate
The N-back task is a sequential-letter memory task for which working memory load is varied, as the respondent must indicate when the current stimulus matches the one from 'n' steps earlier in the sequence. The dependent measure for the N-back task was performance in the 2-back condition, which provides the best index of performance and dorsolateral prefrontal cortex disturbances in subjects with schizophrenia.
Measured: Week 4
AX Continuous Performance Test Task D-prime
For the AX Continuous Performance Test, subjects are required to maintain an attentional set across a delay interval in order to overcome a prepotent response tendency (target responses are required when an X is presented but only in the context of a preceding A; non-target conditions are AY, BX and BY). The dependent measure was d-prime at the long delay (calculated as AX hits minus BX false alarms, which is particularly sensitive to context processing impairments in individuals with schizophrenia.
Measured: Week 4
Preparing to Overcome Prepotency (POP) Task - Reaction Time
The POP task is a cued stimulus-response reversal paradigm that, similar to the AX Continuous Performance Test, requires increases in cognitive control through the maintenance and use of context information to overcome prepotent response tendencies.
Measured: Week 4
Preparing to Overcome Prepotency Task - Error Rate
The POP task is a cued stimulus-response reversal paradigm that, similar to the AX Continuous Performance Test, requires increases in cognitive control through the maintenance and use of context information to overcome prepotent response tendencies.
Measured: Week 4

Secondary outcomes (3)

Brief Psychiatric Rating Scale Total Score
The Brief Psychiatric Rating Scale-anchored (BPRS; Overall and Gorham, 1962; Woerner, Mannuzza, Kane, 1988) is an 18-item scale that is among the most widely used measure of psychopathology. Scores range from 1-7, with higher scores reflecting greater pathology. A total score is derived from the sum of all 18 items (possible scores range from 18-126). It relies on clinical judgment in the assessment of key areas of psychopathology (depression, anxiety, psychosis).
Measured: Week 4
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score
Five index scores are computed from the RBANS (immediate memory, language, visuospatial, attention, delayed memory) that are combined to provide the Total Score. The Total Score is expressed as a standardized score normalized to a population mean of 100, with a standard deviation of 15 (possible scores 40-135). Higher scores reflect better performance. All subjects received the "A" form at baseline and the wk-4 visit and the "B" form at the wk-2 visit (the A/B forms are equivalent alternate forms, which allow for retesting patients without the confound of practice effects).
Measured: Week 4
Repeatable Battery for the Assessment of Neuropsychological Status - Delayed Memory Subindex
The Delayed Memory Index consists of verbal and nonverbal recall tasks (words, drawings) that the subject views early in the evaluation and without warning, is asked to recall ~1/2 hr later. Scores are expressed as standardized scores normalized to a population mean of 100, with a standard deviation of 15 (possible scores between 40-135). Higher scores reflect better performance. Subjects received the "A" form at baseline and wk-4 visit and the "B" form at the wk-2 visit (A/B forms are equivalent alternate forms, which allow for retesting patients without the confound of practice effects).
Measured: Week 4

Timeline

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

Aug 2005Jan 2008

First posted11 Aug 2005 (estimated)
Study startAug 2005
Primary completionJan 2008
Study completionJan 2008

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.
Publications (3)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by University of PittsburghThe 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00129441
Sponsor's protocol ID: 0502027
Status last verified: Oct 2011
First submitted: 10 Aug 2005
Last updated: 17 Oct 2011
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci. 2005 Apr;6(4):312-24. doi: 10.1038/nrn1648.
PubMed 15803162
Lewis DA, Volk DW, Hashimoto T. Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction. Psychopharmacology (Berl). 2004 Jun;174(1):143-50. doi: 10.1007/s00213-003-1673-x. Epub 2003 Dec 9.
PubMed 15205885
Lewis DA, Cho RY, Carter CS, Eklund K, Forster S, Kelly MA, Montrose D. Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry. 2008 Dec;165(12):1585-93. doi: 10.1176/appi.ajp.2008.08030395. Epub 2008 Oct 15.
PubMed 18923067

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 Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Treatment of Cognitive Disability in Schizophrenia With a GABA-A Alpha2/3 Receptor Agonist
ClinicalTrials.gov ID: NCT00129441
Acronym / sponsor ID: 0502027
Conditions: Schizophrenia
Keywords: schizophrenia
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: University of PittsburghUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: Aug 2005
Primary completion: Jan 2008 (actual)
Study completion: Jan 2008 (actual)
First posted: 11 Aug 2005 (estimated)
Results: Posted 17 Oct 2011

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Merck L-830982	Experimental	Drug: Merck L-830982
Sugar pill	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 50 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Male participants
Between the ages of 18 and 50
Meet diagnostic criteria for schizophrenia or schizoaffective disorder
Are clinically stable for a minimum of 3 months on current dose of medication
Are unemployed (i.e., work less than 20 hours per week at competitive employment)

Key exclusion criteria (6 listed)

Psychoactive substance dependence within the past 6 months or substance abuse within the past month
History of head trauma or other neurological disorder
Medical illness or medications, such as benzodiazepine treatment or HIV medications, that may be affected by study participation (the study doctor will discuss this with potential subjects)
Mental retardation
Seizure disorder

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
Merck L-830982Also: MK-0777The initial dose of L-830982 was 3.0 mg twice daily (b.i.d.) the dosage increased to 5.0 mg b.i.d. at the end of week 1 and 8.0 mg b.i.d. at the end of week 2, which was continued for the remaining 2 weeks of the trial. Medications were dispensed weekly in blister packs by the hospital pharmacy.	Drug	Merck L-830982
PlaceboMedications were dispensed weekly in blister packs by the hospital pharmacy, using the same number of pills as those on active drug.	Drug	Sugar pill

Primary outcome

N-back Task - Reaction Time
Time frame: Week 4
The N-back task is a sequential-letter memory task for which working memory load is varied, as the respondent must indicate when the current stimulus matches the one from 'n' steps earlier in the sequence. The dependent measure for the N-back task was performance in the 2-back condition, which provides the best index of performance and dorsolateral prefrontal cortex disturbances in subjects with schizophrenia.
N-back Task - Error Rate
Time frame: Week 4
The N-back task is a sequential-letter memory task for which working memory load is varied, as the respondent must indicate when the current stimulus matches the one from 'n' steps earlier in the sequence. The dependent measure for the N-back task was performance in the 2-back condition, which provides the best index of performance and dorsolateral prefrontal cortex disturbances in subjects with schizophrenia.
AX Continuous Performance Test Task D-prime
Time frame: Week 4
For the AX Continuous Performance Test, subjects are required to maintain an attentional set across a delay interval in order to overcome a prepotent response tendency (target responses are required when an X is presented but only in the context of a preceding A; non-target conditions are AY, BX and BY). The dependent measure was d-prime at the long delay (calculated as AX hits minus BX false alarms, which is particularly sensitive to context processing impairments in individuals with schizophrenia.
Preparing to Overcome Prepotency (POP) Task - Reaction Time
Time frame: Week 4
The POP task is a cued stimulus-response reversal paradigm that, similar to the AX Continuous Performance Test, requires increases in cognitive control through the maintenance and use of context information to overcome prepotent response tendencies.
Preparing to Overcome Prepotency Task - Error Rate
Time frame: Week 4
The POP task is a cued stimulus-response reversal paradigm that, similar to the AX Continuous Performance Test, requires increases in cognitive control through the maintenance and use of context information to overcome prepotent response tendencies.

3 secondary outcomes

Brief Psychiatric Rating Scale Total Score
Time frame: Week 4
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score
Time frame: Week 4
Repeatable Battery for the Assessment of Neuropsychological Status - Delayed Memory Subindex
Time frame: Week 4

Results and safety

Results posted to the registry on 17 Oct 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
L-830982	9	9
Placebo	6	6

Primary outcome: N-back Task - Reaction Time

Time frame: Week 4. Mean (Standard Deviation). Unit: msec

Measure	L-830982 n = 9	Placebo n = 5
Value	786 (231)	684 (101)

L-830982 vs Placebo: p = 0.16, ANOVA

Population analysed: Analyses included only those participants who completed the 4-week trial. One participant refused N-back at week-4, so 9 L-830982 and 5 placebo were analyzed.

Primary outcome: N-back Task - Error Rate

Time frame: Week 4. Mean (Standard Deviation). Unit: proportion of errors

Measure	L-830982 n = 9	Placebo n = 5
Value	0.239 (0.062)	0.297 (0.075)

L-830982 vs Placebo: p = 0.162, ANOVA

Population analysed: Analyses included only those participants who completed the 4-week trial. One participant refused N-back at week-4, so 9 L-830982 and 5 placebo were analyzed.

Primary outcome: AX Continuous Performance Test Task D-prime

Time frame: Week 4. Mean (Standard Deviation). Unit: d-prime

Measure	L-830982 n = 7	Placebo n = 4
Value	1.9 (0.9)	0.7 (0.9)

L-830982 vs Placebo: p = 0.12, ANOVA

Population analysed: Four subjects did not complete a sufficient number of trials for the AXCPT task at both testing periods, therefore 7 L-830982 and 4 placebo subjects data were analyzed.

Primary outcome: Preparing to Overcome Prepotency (POP) Task - Reaction Time

Time frame: Week 4. Mean (Standard Deviation). Unit: msec

Measure	L-830982 n = 9	Placebo n = 6
Value	57 (66)	66 (55)

L-830982 vs Placebo: p = 0.05, ANOVA

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data were collected at all timepoints during the 5-week clinical trial. Eye exams were conducted at 6-month and 1-year follow-ups.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
L-830982	0 of 10 (0%)	4 of 10 (40%)	Not reported
Placebo	0 of 6 (0%)	0 of 6 (0%)	Not reported

Limitations and caveats (from the sponsor): Small sample size; RBANS may lack appropriate sensitivity for short-term study; between-group differences in baseline clinical symptoms \& neuropsychological function; excluding those with more modest cognitive impairments (RBANS standard score \>90).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15803162Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci. 2005 Apr;6(4):312-24. doi: 10.1038/nrn1648.
Background: PubMed 15205885Lewis DA, Volk DW, Hashimoto T. Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction. Psychopharmacology (Berl). 2004 Jun;174(1):143-50. doi: 10.1007/s00213-003-1673-x. Epub 2003 Dec 9.
Results publication: PubMed 18923067Lewis DA, Cho RY, Carter CS, Eklund K, Forster S, Kelly MA, Montrose D. Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry. 2008 Dec;165(12):1585-93. doi: 10.1176/appi.ajp.2008.08030395. Epub 2008 Oct 15.

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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.

David A Lewis, MD principal investigator

University of Pittsburgh

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Merck L-830982 in people with Schizophrenia, run by University of Pittsburgh 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 5 inclusion and 6 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 17 Oct 2011. 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 phase mean?

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 17 Oct 2011). 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?

N-back Task - Reaction Time (time frame: Week 4). The study lists 5 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 NCT00129441, which also lists 3 linked publications.

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 17 Oct 2011.