Clinical trial NCT00255918: Investigation of the Drug Dimethoxbenzylidene Anabaseine in Treating Schizophrenia Patients
Official title: Phase 1 Trial of 3-2,4 Dimethoxbenzylidene Anabaseine in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Psychotic Disorders
Keywords: Evoked Potentials
3-(2,4-dimethoxybenzylidene)anabaseine
DMXB-A
Receptors, Nicotinic
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2005-11-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: Total Scale Score for the Repeatable Battery for the Assessment of Neuropsychological Status
timeFrame: Measured at 2 hours after drug or placebo
Secondary outcomes:
measure: Brief Psychiatric Rating Scale
timeFrame: Measured 4 hours after drug or placebo administration
measure: P50 auditory evoked potential test amplitude/conditioning amplitude ratio
timeFrame: Measured 2.5 hours after drug or placebo administration
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado General Clinical Research Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Robert Freedman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martin LF, Kem WR, Freedman R. Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology (Berl). 2004 Jun;174(1):54-64. doi: 10.1007/s00213-003-1750-1. Epub 2004 Feb 19.