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Nicotinic Receptors and Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
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

July 14, 2011
June 16, 2015
July 2011
June 2015   (final data collection date for primary outcome measure)
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.
Efficacy: Clinical, MATRICS CCB T-score and SANS and BPRS Ratings [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
MATRICS CCB T-score and SANS and BPRS 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.
Complete list of historical versions of study NCT01400477 on ClinicalTrials.gov Archive Site
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
Neurobiological, as measured by fMRI SPEM BOLD signal strength [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Neurobiological, as measured by fMRI SPEM BOLD signal strength at 4 weeks, experimental drug compared to placebo, covaried for baseline measurements at initiation of trial
Not Provided
Not Provided
 
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.
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.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Schizoaffective Disorder
  • Drug: DMXB-A-SR
    Experimental Study Drug: 3-2, 4 dimethoxybenzylidene anabaseine sustained release (DMXB-A-SR)
    Other Name: GTS-21
  • Other: Placebo
    Placebo Comparator
  • 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)
    Intervention: Drug: DMXB-A-SR
  • Placebo Comparator: Arm #2: Placebo Comparator
    Inert capsule to resemble active drug.
    Intervention: Other: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
97
June 2015
June 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01400477
11-0459, 5P50MH086383-02, R01MH061412-05, VA Merit Review grant
Yes
Not Provided
Not Provided
University of Colorado, Denver
University of Colorado, Denver
National Institute of Mental Health (NIMH)
Principal Investigator: Robert Freedman, MD University of Colorado, Denver
University of Colorado, Denver
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP