Clonazepam Effects on Brain Oscillations and Cognition in Schizophrenia

NCT03061136 | Withdrawn Phase 4

• 1 other identifier: YOJ0004ARC
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive deficits are some of the most prominent and disabling symptoms of schizophrenia. Evidence suggests that schizophrenia involves alterations to the functioning of a neural system under the control of a brain chemical called GABA. The present project will compare the effects of low-dose clonazepam (at a sub-sedating dose) to placebo, for effects on GABA- modulated brain activity measured by EEG, and associated cognitive processes in people who have schizophrenia.

Conditions

Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder

Keywords

Cognition; Gamma oscillations; EEG; Executive function; Benzodiazepine; GABA

Outcome Measures

Primary Outcomes (1)

• EEG Gamma-oscillatory power

  Gamma-oscillation power is derived from EEG spectrogram, reflecting underlying brain electrical activity

  1 day

Secondary Outcomes (5)

• EEG derived Auditory steady state power

  1 day

• Brief Psychiatric Rating Scale (BPRS)

  1 day

• Scale for the Assessment of Negative Symptoms (SANS)

  1 day

• Scale for the Assessment of Positive Symptoms (SAPS)

  1 day

• Working memory task accuracy

  1 day

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo administered orally

Drug: Placebo

Clonazepam 0.1mg

EXPERIMENTAL

0.1mg clonazepam administered orally

Drug: Clonazepam

Clonazepam 0.2mg

EXPERIMENTAL

0.2mg clonazepam administered orally

Drug: Clonazepam

Clonazepam 0.3mg

EXPERIMENTAL

0.3mg clonazepam administered orally

Drug: Clonazepam

Interventions

Clonazepam DRUG

Also known as: Klonopin

Clonazepam 0.1mg; Clonazepam 0.2mg; Clonazepam 0.3mg

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects will be included if they are adults (18-55 years old) who currently meet criteria for schizophrenia, schizophreniform disorder or schizoaffective disorder from the DSM-IV (295.X).
• Healthy control subjects: 18-55 years of age.

You may not qualify if:

• All subjects will be excluded if they have a history of any substance-related disorder (by DSM-IV, other than cannabis abuse) in the prior 6 months, or repeated positive urine drug screens for other illicit substances. They will also be excluded if they are clinically-unstable, have significant baseline or emergent suicide risk (by Columbia Suicide Severity Risk Scale), estimated IQ \< 70, or EEG contraindications. Subjects must also have no major medical or neurological illness, or significant head trauma.
• Excluded medications:
• Prospective subjects will be excluded if they are currently in treatment with benzodiazepines, anticonvulsants, and medications such as zolpidem and baclofen, each of which directly affect GABA neurons or may be associated with changes in GABA system function.
• Healthy controls must be free of a diagnosis of a chronic or recurrent Axis I (or certain Axis II) psychiatric disorder and will be excluded if they have a first degree relative with a psychotic disorder.

Sponsors & Collaborators

• Palo Alto Veterans Institute for Research: lead
• Stanford University: collaborator
• University of California, Los Angeles: collaborator

Study Sites (1)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

Related Publications (5)

• Bowie CR, Harvey PD. Cognition in schizophrenia: impairments, determinants, and functional importance. Psychiatr Clin North Am. 2005 Sep;28(3):613-33, 626. doi: 10.1016/j.psc.2005.05.004.

  PMID: 16122570 BACKGROUND

• Minzenberg MJ, Carter CS. Developing treatments for impaired cognition in schizophrenia. Trends Cogn Sci. 2012 Jan;16(1):35-42. doi: 10.1016/j.tics.2011.11.017. Epub 2011 Dec 16.

  PMID: 22178120 BACKGROUND

• Lesh TA, Niendam TA, Minzenberg MJ, Carter CS. Cognitive control deficits in schizophrenia: mechanisms and meaning. Neuropsychopharmacology. 2011 Jan;36(1):316-38. doi: 10.1038/npp.2010.156. Epub 2010 Sep 15.

  PMID: 20844478 BACKGROUND

• Minzenberg MJ, Laird AR, Thelen S, Carter CS, Glahn DC. Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Arch Gen Psychiatry. 2009 Aug;66(8):811-22. doi: 10.1001/archgenpsychiatry.2009.91.

  PMID: 19652121 BACKGROUND

• Cho KK, Hoch R, Lee AT, Patel T, Rubenstein JL, Sohal VS. Gamma rhythms link prefrontal interneuron dysfunction with cognitive inflexibility in Dlx5/6(+/-) mice. Neuron. 2015 Mar 18;85(6):1332-43. doi: 10.1016/j.neuron.2015.02.019. Epub 2015 Mar 5.

  PMID: 25754826 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Clonazepam

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 15, 2017
• First Posted: February 23, 2017
• Study Start: October 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: April 5, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)