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Nicotinic Receptors and Schizophrenia

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
DMXB-A-SR
Placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Drug Trial, Smoking, Smoking Cessation, Cognition, Mental Focus

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects will be selected to be 18 to 65 years old and in good general health.
  • Subjects who fulfill Diagnostic and Statistical Manual -IV-Text Revision (DSM-IV-TR) criteria for schizophrenia or schizoaffective disorder.
  • Smokers will smoke at least 20 cigarettes per day.
  • Non-smokers will also be enrolled.

  • Subjects will have normal:

    • vital signs,
    • hematology,
    • serum chemistries,
    • EKG, and
    • urinalysis with a negative drug screen before entry into the study.
  • Subjects will be fluent in English.
  • Smoking subjects will be interested in stopping smoking in the near future and not interested in nicotine replacement therapy.

Exclusion Criteria:

  • Subjects with histories of:

    • neurological illness,
    • liver disease,
    • severe hypertension (cut-off blood pressure 160/100) or
    • cardiac disease, or
    • renal failure (cut-off creatinine above 1.4).
  • Subjects who currently meet DSM-IV-TR criteria for substance dependence other than nicotine, cannabis, or alcohol will be excluded.
  • Women who are capable of pregnancy and not on acceptable forms of birth control will be excluded.
  • Subjects being treated with Clozapine will be excluded.

Sites / Locations

  • UColorado Denver
  • University of Colorado-Anschutz Medical Campus, Department of Psychiatry

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

DMXB-A-SR

Arm #2: Placebo Comparator

Arm Description

Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR), 3-2, 4 dimethoxybenzylidene anabaseine sustained release (GTS-21)

Inert capsule to resemble active drug.

Outcomes

Primary Outcome Measures

Neurocognitive Efficacy
MATRICS CCB Neurocognitive T-score (Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery Statistically Adjusted-score). Higher scores indicate better neurocognitive functionality.

Secondary Outcome Measures

Inhibition of Auditory Evoked Potential P50 to Repeated Stimuli
The P50 evoked response paired of auditory stimuli S1, S2, is measured. The inhibition is expressed as the ratio P50 S2 amplitude divided by P50 S1 amplitude.

Full Information

First Posted
July 14, 2011
Last Updated
April 15, 2019
Sponsor
University of Colorado, Denver
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT01400477
Brief Title
Nicotinic Receptors and Schizophrenia
Official Title
Nicotinic Receptors and Schizophrenia: Phase II
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators hypothesize that sustained-release DMXB-A-SR (3-2,4 dimethoxybenzylidene anabaseine sustained release) will provide clinical improvement in cognition in patients with schizophrenia who are smokers and who are non-smokers. The study drug may also maintain abstinence from cigarette smoking and improve other symptoms in patients with schizophrenia.
Detailed Description
Patients with schizophrenia will be screened then enrolled for one week placebo trial in addition to their existing antipsychotic medication. If pill compliance is greater than 80%, then they will receive baseline clinical, cognitive, and brain imaging and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram. Then patients will receive in a randomized double blind trial either DMXB-A-SR (3-2,4 dimethoxybenzylidene anabaseine sustained release) or placebo comparator in addition to their existing antipsychotic medication. After one month patients will receive repeat clinical, cognitive, and brain imaging testing and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
Drug Trial, Smoking, Smoking Cessation, Cognition, Mental Focus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Random allocation to a treatment and placebo group.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
The pharmacist places the treatment or placebo into identical coded vials. Only the pharmacist and the statistician have the code to identify of the treatment.
Allocation
Randomized
Enrollment
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DMXB-A-SR
Arm Type
Experimental
Arm Description
Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR), 3-2, 4 dimethoxybenzylidene anabaseine sustained release (GTS-21)
Arm Title
Arm #2: Placebo Comparator
Arm Type
Placebo Comparator
Arm Description
Inert capsule to resemble active drug.
Intervention Type
Drug
Intervention Name(s)
DMXB-A-SR
Other Intervention Name(s)
GTS-21
Intervention Description
Experimental Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo Comparator
Primary Outcome Measure Information:
Title
Neurocognitive Efficacy
Description
MATRICS CCB Neurocognitive T-score (Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery Statistically Adjusted-score). Higher scores indicate better neurocognitive functionality.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Inhibition of Auditory Evoked Potential P50 to Repeated Stimuli
Description
The P50 evoked response paired of auditory stimuli S1, S2, is measured. The inhibition is expressed as the ratio P50 S2 amplitude divided by P50 S1 amplitude.
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects will be selected to be 18 to 65 years old and in good general health. Subjects who fulfill Diagnostic and Statistical Manual -IV-Text Revision (DSM-IV-TR) criteria for schizophrenia or schizoaffective disorder. Smokers will smoke at least 20 cigarettes per day. Non-smokers will also be enrolled. Subjects will have normal: vital signs, hematology, serum chemistries, EKG, and urinalysis with a negative drug screen before entry into the study. Subjects will be fluent in English. Smoking subjects will be interested in stopping smoking in the near future and not interested in nicotine replacement therapy. Exclusion Criteria: Subjects with histories of: neurological illness, liver disease, severe hypertension (cut-off blood pressure 160/100) or cardiac disease, or renal failure (cut-off creatinine above 1.4). Subjects who currently meet DSM-IV-TR criteria for substance dependence other than nicotine, cannabis, or alcohol will be excluded. Women who are capable of pregnancy and not on acceptable forms of birth control will be excluded. Subjects being treated with Clozapine will be excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Freedman, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
UColorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Colorado-Anschutz Medical Campus, Department of Psychiatry
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual patient description can be obtained from Robert.Freedman@ucdenver.edu. It will be available December 1, 2017.
Citations:
PubMed Identifier
16754836
Citation
Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R. Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry. 2006 Jun;63(6):630-8. doi: 10.1001/archpsyc.63.6.630.
Results Reference
background
PubMed Identifier
18381905
Citation
Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L, Allensworth D, Guzman-Bonilla A, Clement B, Ball MP, Kutnick J, Pender V, Martin LF, Stevens KE, Wagner BD, Zerbe GO, Soti F, Kem WR. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry. 2008 Aug;165(8):1040-7. doi: 10.1176/appi.ajp.2008.07071135. Epub 2008 Apr 1.
Results Reference
background
PubMed Identifier
28825423
Citation
Kem WR, Olincy A, Johnson L, Harris J, Wagner BD, Buchanan RW, Christians U, Freedman R. Pharmacokinetic Limitations on Effects of an Alpha7-Nicotinic Receptor Agonist in Schizophrenia: Randomized Trial with an Extended-Release Formulation. Neuropsychopharmacology. 2018 Feb;43(3):583-589. doi: 10.1038/npp.2017.182. Epub 2017 Aug 21.
Results Reference
derived
Links:
URL
http://www.ucdenver.edu/academics/colleges/medicalschool/departments/psychiatry/Pages/PsychiatryWelcome.aspx
Description
Welcome site

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Nicotinic Receptors and Schizophrenia

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