Addition of Ondansetron to Ongoing Antipsychotic Treatment for Schizophrenia

A Phase 3 study of Schizophrenia, run by University of Colorado, Denver at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study will examine the effects of ondansetron on auditory nerve activity in people with schizophrenia who are being treated with new antipsychotics. Read more about this study

Who is it for?: Ages 18 to 55 years
Conditions the study is for: Schizophrenia
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 8 participants
Where: 1 siteUnited States
Study dates: Jan 2005to May 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Meets DSM-IV criteria for schizophrenia
Stable, chronic schizophrenia
Currently taking atypical medications
Use of effective form of contraception throughout study

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Denver VAMC
Denver, Colorado, 80220

Other trials in United States

About this study

Official title: Atypical Antipsychotics and P50 Sensory Gating

This study will examine the effects of ondansetron on auditory nerve activity in people with schizophrenia who are being treated with new antipsychotics.

Read the 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.

Conditions: Schizophrenia
Being tested: Ondansetron followed by placebo, Placebo followed by Ondansetron
Keywords: Schizophrenia, Ondansetron, P50 sensory gating, Evoked potentials, 5-HT3 receptors, Atypical antipsychotics
Medical subject headings: Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ondansetron followed by placeboDrug
Also called Zofran, Zuplenz
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.
Placebo followed by OndansetronDrug
Also called Zofran, Zuplenz
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.

Study groups in NCT00149734
Study group	Role	What they receive
Ondansetron followed by placebo	Experimental	Participants will take ondansetron then placebo plus an atypical antipsychotic drug Receives: Drug: Ondansetron followed by placebo
Placebo followed by Ondansetron	Experimental	Participants will take placebo then ondansetron plus an atypical antipsychotic drug Receives: Drug: Placebo followed by Ondansetron

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to 3 hours
Cognitive Testing
Measured: Measured at Months 3 and 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2005May 2010

First posted8 Sep 2005 (estimated)
Study startJan 2005
Primary completionMay 2010
Study completionMay 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by University of Colorado, DenverThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00149734
Sponsor's protocol ID: 04-0255
Other IDs: R01MH050787, COMIRB # 04-0255, DNBBS 73-MCR
Status last verified: Jul 2021
First submitted: 6 Sep 2005
Last updated: 13 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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. doi: 10.1176/appi.ajp.162.2.386.
PubMed 15677607
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. doi: 10.1176/ajp.161.10.1822.
PubMed 15465979

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Atypical Antipsychotics and P50 Sensory Gating
ClinicalTrials.gov ID: NCT00149734
Acronym / sponsor ID: 04-0255
Conditions: Schizophrenia
Keywords: Schizophrenia, Ondansetron, P50 sensory gating, Evoked potentials, 5-HT3 receptors, Atypical antipsychotics
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: University of Colorado, DenverUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: Jan 2005
Primary completion: May 2010 (actual)
Study completion: May 2010 (actual)
First posted: 8 Sep 2005 (estimated)
Results: Posted 13 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Ondansetron followed by placebo	Experimental	Drug: Ondansetron followed by placeboParticipants will take ondansetron then placebo plus an atypical antipsychotic drug
Placebo followed by Ondansetron	Experimental	Drug: Placebo followed by OndansetronParticipants will take placebo then ondansetron plus an atypical antipsychotic drug

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Meets DSM-IV criteria for schizophrenia
Stable, chronic schizophrenia
Currently taking atypical medications
Use of effective form of contraception throughout study

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ondansetron followed by placeboAlso: Zofran, ZuplenzParticipants 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.	Drug	Ondansetron followed by placebo
Placebo followed by OndansetronAlso: Zofran, ZuplenzParticipants 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.	Drug	Placebo followed by Ondansetron

Primary outcome

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.
Cognitive Testing
Time frame: Measured at Months 3 and 6

Results and safety

Results posted to the registry on 13 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ondansetron Followed by Placebo	4	4
Placebo Followed by Ondansetron	4	4

Primary outcome: P50 Sensory Gating

Time frame: Up to 3 hours. Mean (Standard Deviation). Unit: percentage

Measure	Ondansetron n = 8	Placebo n = 8
Value	41.4 (39.7)	80.2 (21.3)

Primary outcome: Cognitive Testing

Time frame: Measured at Months 3 and 6

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

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ondansetron	0 of 0	0 of 0	Not reported
Placebo	0 of 0	0 of 0	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15677607Adler 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. doi: 10.1176/appi.ajp.162.2.386.
Background: PubMed 15465979Adler 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. doi: 10.1176/ajp.161.10.1822.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lawrence E. Adler, MD principal investigator

University of Colorado Health Sciences Center, VISN19 MIRECC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study of Schizophrenia, run by University of Colorado, Denver at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

P50 Sensory Gating (time frame: Up to 3 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00149734, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2021.