Addition of Ondansetron to Ongoing Antipsychotic Treatment for Schizophrenia

• ClinicalTrials.gov Identifier: NCT00149734
• Recruitment Status: Completed
• First Posted: September 8, 2005
• Results First Posted: August 13, 2021
• Last Update Posted: August 13, 2021
• Sponsor: University of Colorado, Denver
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Ondansetron followed by placebo; Drug: Placebo followed by Ondansetron	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Atypical Antipsychotics and P50 Sensory Gating
• Study Start Date: January 2005
• Actual Primary Completion Date: May 2010
• Actual Study Completion Date: May 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ondansetron followed by placebo; Participants will take ondansetron then placebo plus an atypical antipsychotic drug	Drug: Ondansetron 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.; Other Name: Zofran, Zuplenz
Experimental: Placebo followed by Ondansetron; Participants will take placebo then ondansetron plus an atypical antipsychotic drug	Drug: Placebo 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.; Other Name: Zofran, Zuplenz

Outcome Measures

Primary Outcome Measures :

1. P50 Sensory Gating [ Time Frame: 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.
2. Cognitive Testing [ Time Frame: Measured at Months 3 and 6 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Colorado

Denver VAMC

Denver, Colorado, United States, 80220

Sponsors and Collaborators

University of Colorado, Denver

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Lawrence E. Adler, MD; University of Colorado Health Sciences Center, VISN19 MIRECC

More Information

Publications:

Adler LE, Cawthra EM, Donovan KA, Harris JG, Nagamoto HT, Olincy A, Waldo MC. Improved p50 auditory gating with ondansetron in medicated schizophrenia patients. Am J Psychiatry. 2005 Feb;162(2):386-8.

Adler LE, Olincy A, Cawthra EM, McRae KA, Harris JG, Nagamoto HT, Waldo MC, Hall MH, Bowles A, Woodward L, Ross RG, Freedman R. Varied effects of atypical neuroleptics on P50 auditory gating in schizophrenia patients. Am J Psychiatry. 2004 Oct;161(10):1822-8.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT00149734
• Other Study ID Numbers: 04-0255; R01MH050787 ( U.S. NIH Grant/Contract ); COMIRB # 04-0255; DNBBS 73-MCR
• First Posted: September 8, 2005
• Results First Posted: August 13, 2021
• Last Update Posted: August 13, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Colorado, Denver:

Schizophrenia; Ondansetron; P50 sensory gating; Evoked potentials; 5-HT3 receptors; Atypical antipsychotics

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Ondansetron; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipruritics; Dermatologic Agents; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Anti-Anxiety Agents