Nicotinic Receptors and Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01400477
First received: July 14, 2011
Last updated: June 16, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: DMXB-A-SR
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Nicotinic Receptors and Schizophrenia: Phase II

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Efficacy: Clinical, Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MATRICS CCB) T-score and Scale for the Assessment of Negative Symptoms) SANS and Brief Psychiatric Rating Scale (BPRS) Ratings [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    MATRICS CCB T-score (Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery Statistically Adjusted-score) and SANS (Scale for Assessment of Negative Symptoms) and BPRS (Brief Psychiatric Rating Scale) rating; data for primary outcome measures are collected at "baseline" study visit and last study visit, 4 weeks post-"baseline" visit. The primary analysis compares values at 4 weeks, covaried for baseline measurements. A new algorithm for computing the MATRICS CCB Overall Composite T-Score using only six cognitive domains and omitting the Social Cognition domain will be used to compute the primary outcome. Non-smoking and smoking subjects will be compared and for efficacy of the drug on cognition.


Secondary Outcome Measures:
  • Neurobiological, as measured by Functional Magnetic Resonance Imaging (fMRI) Smooth Pursuit Eye Movement (SPEM) BOLD signal strength [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Neurobiological, as measured by fMRI Smooth Pursuit Eye Movement (SPEM) BOLD (Functional Magnetic Resonance Imaging Smooth Pursuit Eye Movement Blood Oxygenation Level Dependent Signal ) signal strength at 4 weeks, experimental drug compared to placebo, covaried for baseline measurements at initiation of trial. Nonsmoking and smoking subjects will be compared for the ability of the drug to change fMRI bold signal strength


Enrollment: 97
Study Start Date: July 2011
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: GTS-21
Placebo Comparator: Arm #2: Placebo Comparator
Inert capsule to resemble active drug.
Other: Placebo
Placebo Comparator

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 they 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 they will receive repeat clinical, cognitive, and brain imaging testing and all clinical laboratory examinations and a physical examination, vital signs, and cardiogram.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects will be selected to be 18 to 65 years old and in good general health.
  • We will include people 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) will be excluded.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01400477

Locations
United States, Colorado
UColorado Denver
Aurora, Colorado, United States, 80045
University of Colorado-Anschutz Medical Campus, Department of Psychiatry
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Robert Freedman, MD University of Colorado, Denver
  More Information

Additional Information:
Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01400477     History of Changes
Other Study ID Numbers: 11-0459, 5P50MH086383-02, R01MH061412-05, VA Merit Review grant
Study First Received: July 14, 2011
Last Updated: June 16, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Drug Trial
Smoking
Smoking Cessation
Cognition
Mental Focus

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on September 02, 2015