Addition of Ondansetron to Ongoing Antipsychotic Treatment for Schizophrenia

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT00149734
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 63.9
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Jan 1, 2005
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 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 Names: 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 Names: Zofran, Zuplenz

Outcome Measures

Primary Outcome Measures

1. 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.

2. Cognitive Testing [Measured at Months 3 and 6]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

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; COMIRB # 04-0255; DNBBS 73-MCR
• First Posted: Sep 8, 2005
• Last Update Posted: Aug 13, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Ondansetron

Study Results

Participant Flow

Arm/Group Title	Ondansetron Followed by Placebo	Placebo Followed by Ondansetron
Arm/Group Description	Participants will take ondansetron (16mg) at one study visit, then a placebo at another study visit one week later.	Participants will take a placebo at one study visit, then ondansetron (16mg) at another study visit one week later.
Period Title: Overall Study
STARTED	4	4
Started Intervention 2	4	4
COMPLETED	4	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Ondansetron followed by placebo group and Placebo followed by Ondansetron group
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.5 (5.9)
Sex: Female, Male (Count of Participants)
Female	4 50%
Male	4 50%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	P50 Sensory Gating
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ondansetron	Placebo
Arm/Group Description	Ondansetron (16 mg)	Placebo
Measure Participants	8	8
Mean (Standard Deviation) [percentage]	41.4 (39.7)	80.2 (21.3)

2. Primary Outcome

Title	Cognitive Testing
Time Frame	Measured at Months 3 and 6

Outcome Measure Data

Analysis Population Description

this outcome measure was not collected due to a change in the study design via a protocol amendment.

Arm/Group Title	Ondansetron	Placebo
Arm/Group Description	Ondansetron (16 mg)	Placebo
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	No adverse events data is available. The PI has left the university and has confirmed that he no longer has access to the data, and the remaining members of the study team confirmed that the data no longer exists. Therefore, the number of participants "At risk" is 0, because no participants could be analyzed for adverse events.
Arm/Group Title	Ondansetron		Placebo
Arm/Group Description	Ondansetron (16 mg)		Placebo
All Cause Mortality
	Ondansetron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ondansetron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Ondansetron		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Limited data is available. The PI has left the university and has confirmed that he no longer has access to the data, and the remaining members of the study team confirmed that the data no longer exists. The study design was altered after registration due to a protocol amendment to not do a long-term study but to directly study participants on long-term clozapine treatment (a 5HT3 receptor antagonist like ondansetron) with other antipsychotics, including atypicals.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.