Nicotinic Receptors and Schizophrenia

Nicotinic Receptors and Schizophrenia: Phase II

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Other: Placebo; Drug: DMXB-A-SR

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.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UColorado Denver
    • Aurora, Colorado, United States, 80045
      • University of Colorado-Anschutz Medical Campus, Department of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DMXB-A-SR; Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR), 3-2, 4 dimethoxybenzylidene anabaseine sustained release (GTS-21)	Drug: DMXB-A-SR; Experimental Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR); Other Names: GTS-21
Placebo Comparator: Arm #2: Placebo Comparator; Inert capsule to resemble active drug.	Other: Placebo; Placebo Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Robert Freedman, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• Welcome site

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 14, 2011
• First Submitted That Met QC Criteria: July 20, 2011
• First Posted (Estimate): July 22, 2011

Study Record Updates

• Last Update Posted (Actual): May 7, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Smoking; Cognition; Smoking Cessation; Drug Trial; Mental Focus
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: 11-0459; VA Merit Review grant (Other Grant/Funding Number: VA Merit Review grant); 5P50MH086383-02 (U.S. NIH Grant/Contract); R01MH061412-05 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual patient description can be obtained from Robert.Freedman@ucdenver.edu. It will be available December 1, 2017.