Investigation of the Drug Dimethoxbenzylidene Anabaseine in Treating Schizophrenia Patients

Schizophrenia Clinical Trial

Official title:

Phase 1 Trial of 3-2,4 Dimethoxbenzylidene Anabaseine in Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00255918
• Other study ID #: 03-0857
• Secondary ID: R01MH061412DNBBS
• Status: Completed
• Phase: Phase 1
• First received: November 16, 2005
• Last updated: June 30, 2015
• Start date: March 2004
• Est. completion date: October 2005

Study information

• Verified date: June 2015
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 2005
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mental Disorders
• Psychotic Disorders
• Schizophrenia

Intervention

Drug:
• Dimethoxybenzylidene anabaseine (DMXB-A)
DMXB-A 150 mg immediate release followed by DMXB-A 75 mg 2 hours after the intiial dose
• Placebo
Placebo dosed to match active medication
• Dimethoxybenzylidene anabaseine (DMXB-A)
DMXB-A 75 mg immediate release followed by DMXB-A 37.5 mg 2 hours after the intiial dose

Locations

Country	Name	City	State
United States	University of Colorado General Clinical Research Center	Denver	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Epub 2004 Feb 19. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Scale Score for the Repeatable Battery for the Assessment of Neuropsychological Status	ten subtests which give five scores, one for each of the five domains tested (immediate memory, visuospatial/constructional, language, attention, delayed memory).	Measured at 2 hours after drug or placebo	No
Secondary	Brief Psychiatric Rating Scale	Brief Psychiatric Rating Scale (BPRS) is a rating scale used to measure psychiatric symptoms	Measured 4 hours after drug or placebo administration	No
Secondary	P50 auditory evoked potential test amplitude/conditioning amplitude ratio	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.	Measured 2.5 hours after drug or placebo administration	No