Schizophrenia
Conditions
Keywords
Schizophrenia, Ondansetron, P50 sensory gating, Evoked potentials, 5-HT3 receptors, Atypical antipsychotics
Brief summary
This study will examine the effects of ondansetron on auditory nerve activity in people with schizophrenia who are being treated with new antipsychotics.
Detailed description
Schizophrenia is a devastating brain disorder. Most people with schizophrenia have difficulty filtering out unimportant auditory information. They have an inability to appropriately inhibit, or gate, sensory information that enters the ear. Standard treatments do not address this problem. When the drug ondansetron is taken in addition to typical antipsychotic drugs, P50 auditory gating improves. However, ondansetron has not been used with some of the newer, atypical antipsychotic drugs. This study will evaluate the effect of combining ondansetron with newer, atypical antipsychotic drugs on P50 auditory gating. Participants in this double-blind study will be randomly assigned to receive either ondansetron or placebo for 3 months. Upon completion of the first 3 months, participants will be crossed over to receive the other treatment for an additional 3 months. All participants will also take an atypical antipsychotic drug, including olanzapine, quetiapine, or aripiprazole. Auditory gating will be assessed using computerized cognitive testing and functional magnetic resonance imaging (fMRI) at baseline and Months 3 and 6. Vital signs and evoked potentials will be assessed at Weeks 1, 3, and 6. Clinical symptoms and cognitive abilities will also be evaluated to determine the effectiveness of ondansetron.
Interventions
DRUGOndansetron followed by placebo
Participants will take 16mg of ondansetron daily for the first three months followed by 3 months of placebo. An atypical antipsychotic drug (olanzapine,quetiapine, or aripiprazole) will also be taken throughout the 6 months treatment period.
DRUGPlacebo followed by Ondansetron
Participants will take placebo daily for the first three months followed by 3 months of 16mg of ondansetron daily. An atypical antipsychotic drug (olanzapine,quetiapine, or aripiprazole) will also be taken throughout the 6 months treatment period.
Sponsors
National Institute of Mental Health (NIMH)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Meets DSM-IV criteria for schizophrenia * Stable, chronic schizophrenia * Currently taking atypical medications * Use of effective form of contraception throughout study
Exclusion criteria
* History of any alcohol or drug abuse within 3 months of study start date * Any other major neurological disorders * History of or current head trauma * Any medical conditions affecting the central nervous system * Current epilepsy, asthma, migraine headache, previous myocardial infarction, stroke, diabetes, hypertension, narrow angle glaucoma, or neuromuscular illnesses * Pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| P50 Sensory Gating | Up to 3 hours | P50 Sensory Gating as measured by evoked potentials (response to stimuli, in this case, clicking sounds).The P50 potential was identified and measured using a computer algorithm. The amplitude of the P50 test wave was divided by the amplitude of the P50 conditioning wave, expressed as a percentage: the P50 ratio. Lower P50 ratios represent better outcomes. |
| Cognitive Testing | Measured at Months 3 and 6 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Ondansetron followed by placebo group and Placebo followed by Ondansetron group | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 5.9 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Cognitive Testing
Time frame: Measured at Months 3 and 6
Population: this outcome measure was not collected due to a change in the study design via a protocol amendment.
Primary
P50 Sensory Gating
P50 Sensory Gating as measured by evoked potentials (response to stimuli, in this case, clicking sounds).The P50 potential was identified and measured using a computer algorithm. The amplitude of the P50 test wave was divided by the amplitude of the P50 conditioning wave, expressed as a percentage: the P50 ratio. Lower P50 ratios represent better outcomes.
Time frame: Up to 3 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ondansetron | P50 Sensory Gating | 41.4 percentage | Standard Deviation 39.7 |
| Placebo | P50 Sensory Gating | 80.2 percentage | Standard Deviation 21.3 |