Investigation of the Drug Dimethoxbenzylidene Anabaseine in Treating Schizophrenia Patients

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00255918
First received: November 16, 2005
Last updated: June 30, 2015
Last verified: June 2015
  Purpose

This study will determine the effectiveness of a drug, dimethoxbenzylidene anabaseine, in producing beneficial effects similar to that of nicotine in individuals with schizophrenia.


Condition Intervention Phase
Schizophrenia
Psychotic Disorders
Drug: Dimethoxybenzylidene anabaseine (DMXB-A)
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 1 Trial of 3-2,4 Dimethoxbenzylidene Anabaseine in Schizophrenia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Total Scale Score for the Repeatable Battery for the Assessment of Neuropsychological Status [ Time Frame: Measured at 2 hours after drug or placebo ] [ Designated as safety issue: No ]
    ten subtests which give five scores, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, delayed memory).


Secondary Outcome Measures:
  • Brief Psychiatric Rating Scale [ Time Frame: Measured 4 hours after drug or placebo administration ] [ Designated as safety issue: No ]
    Brief Psychiatric Rating Scale (BPRS) is a rating scale used to measure psychiatric symptoms

  • P50 auditory evoked potential test amplitude/conditioning amplitude ratio [ Time Frame: Measured 2.5 hours after drug or placebo administration ] [ Designated as safety issue: No ]
    The evoked response amplitude measured in mV to the initial auditory stimulus which is compared to the evoked response amplitude which is measured in mV to a second auditory stimulus that occurs 500 ms later.


Enrollment: 12
Study Start Date: March 2004
Study Completion Date: October 2005
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dimethoxybenzylidene anabaseine 75 mg
Participants will take active experimental medication (Dimethoxybenzylidene anabaseine (DMXB-A) 75 mg)
Drug: Dimethoxybenzylidene anabaseine (DMXB-A)
DMXB-A 150 mg immediate release followed by DMXB-A 75 mg 2 hours after the intiial dose
Drug: Placebo
Placebo dosed to match active medication
Drug: Dimethoxybenzylidene anabaseine (DMXB-A)
DMXB-A 75 mg immediate release followed by DMXB-A 37.5 mg 2 hours after the intiial dose
Placebo Comparator: Placebo
Participants will take placebo.
Drug: Dimethoxybenzylidene anabaseine (DMXB-A)
DMXB-A 150 mg immediate release followed by DMXB-A 75 mg 2 hours after the intiial dose
Drug: Placebo
Placebo dosed to match active medication
Drug: Dimethoxybenzylidene anabaseine (DMXB-A)
DMXB-A 75 mg immediate release followed by DMXB-A 37.5 mg 2 hours after the intiial dose
Experimental: Dimethoxybenzylidene anabaseine 150 mg
Participants will take active experimental medication (Dimethoxybenzylidene anabaseine (DMXB-A) 150 mg)
Drug: Dimethoxybenzylidene anabaseine (DMXB-A)
DMXB-A 150 mg immediate release followed by DMXB-A 75 mg 2 hours after the intiial dose
Drug: Placebo
Placebo dosed to match active medication
Drug: Dimethoxybenzylidene anabaseine (DMXB-A)
DMXB-A 75 mg immediate release followed by DMXB-A 37.5 mg 2 hours after the intiial dose

Detailed Description:

Schizophrenia is a chronic and severe brain disorder that can significantly impact quality of life. It is characterized by delusions, paranoia, and disordered thinking. The cause of schizophrenia has not yet been determined. However, there are many treatments, including drug therapy and cognitive behavioral therapy, that may help to alleviate symptoms of the condition. Nicotinic receptors are involved in a number of biological processes; they are numerous throughout the central and peripheral nervous systems and are diverse in structure and expression. Genetic and neurobiological research has identified decreased expression of the a7 nicotinic receptor as an element in schizophrenia that is related to poor psychosocial outcome. Data indicate that drug therapy may reduce this deficit in receptor expression. Nicotine has been found to stimulate the a7 nicotinic receptor; however, the physiological dependence associated with nicotine makes it an undesirable option. Dimethoxbenzylidene anabaseine (DMXB-A) can stimulate the a7 nicotinic receptor; its advantages include easy oral administration and the lack of dependence-causing effects. This study will determine whether DMXB-A can safely and effectively stimulate the a7 nicotinic receptor in schizophrenia patients and reduce their neurobiological symptoms.

This study will last 6 weeks. Participants will have study visits each week for the duration of the study. During each visit, participants will be randomly assigned to receive either DMXB-A or placebo. An electrocardiogram (EKG) will measure the heart function of participants and participants' blood pressure will be measured. After the first dose of either DMXB-A or placebo, participants will receive a second dose 2 hours later. An evoked potential test, which measures the brain's response to stimuli, will be performed after both doses. Neuropsychological tests, such as verbal reasoning and visual retention, will be performed following the second dose of either DMXB-A or placebo.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of schizophrenia

Exclusion Criteria:

  • History of cardiovascular illness or neurological illness other than schizophrenia
  • Current substance abuse, including nicotine
  • History of clozapine use
  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: NCT00255918

Locations
United States, Colorado
University of Colorado General Clinical Research Center
Denver, Colorado, United States, 80262
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Robert Freedman, MD University of Colorado, Denver
  More Information

Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00255918     History of Changes
Other Study ID Numbers: 03-0857, R01MH061412, DNBBS MC-R
Study First Received: November 16, 2005
Last Updated: June 30, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Evoked Potentials
3-(2,4-dimethoxybenzylidene)anabaseine
DMXB-A
Receptors, Nicotinic

Additional relevant MeSH terms:
Mental Disorders
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
3-(2,4-dimethoxybenzylidene)anabaseine
Cholinergic Agents
Cholinergic Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nicotinic Agonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2015