Brain FunctionPhase 1NCT02460341
The Effects of Ondansetron on Brain Function
A Phase 1 study testing ondansetron in people with Brain Function and Healthy Adults, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
This project investigates the effects of a single dose of ondansetron on brain function in healthy adults. The investigators hypothesize that there will be a dose-dependent reduction in activation of the insula and somatosensory brain regions associated with the use of ondansetron. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Brain Function, Healthy Adults
- What is being tested?
- ondansetron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2015to 3 Feb 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All subjects must be medically healthy, between 18 and 60 years of age, and fluent (speaking and writing) in English
Who cannot join
- Present or previous diagnosis of any psychiatric disorder or major developmental disorder (autism/Asperger's disorder, pervasive developmental disorder), based on psychiatric evaluation using the Mini International Neuropsychiatric Interview (M.I.N.I.) or Structured Clinical Interview for DSM disorders (SCID)
- Any disability or health problem that prevents them from completing study procedures (e.g. color blindness, severe carpal tunnel syndrome, etc.)
- History of organic mental syndromes, head trauma, migraines, seizures, other CNS neurological disease, recent use of illegal drugs or current substance dependence, or significant medical illness other than that listed above (by self-report)
- Pregnant or nursing women
- Subjects with a medical condition or other predisposition that increases the risk of adverse effects when taking ondansetron. These include individuals with drug allergies or known hypersensitivity to ondansetron (or other 5-HT3 antagonists), heart disease, congestive heart failure, heart rhythm disorder, congenital long QT syndrome, electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia) or hepatic impairment
- Subjects who report taking apomorphine will be excluded
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- Subjects with abnormal EKG will either be excluded from participation, or referred to a cardiologist for further assessment of eligibility
- Subjects with abnormal liver function or electrolytes (as determined by blood test) will be excluded from participation if a study team physician determines it is unsafe for them to participate
- Cross-reactivity with other 5-HT3 antagonists has been reported, so any individual taking a 5-HT3 antagonist will be excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
This project investigates the effects of a single dose of ondansetron on brain function in healthy adults. The investigators hypothesize that there will be a dose-dependent reduction in activation of the insula and somatosensory brain regions associated with the use of ondansetron.
Read the detailed description
Objectives:
The overall objective of this study is to examine the effects of single doses of 8 mg, 16 mg, and 24 mg ondansetron as compared to placebo on neural mechanisms of cognition and perception in healthy individuals.
Background:
Many psychiatric disorders are associated with altered sensory experiences arising from within the body. Examples include increased experience of sensations or urges in muscles, skins, joints or visceral organs in tic disorders, OCD patients with symptoms of "not just right experiences" or disgust sensitivity, and impulse control disorders (ICDs) such as trichotillomania or skin-picking. In OCD, sensory phenomena occur in approximately half of patients, are associated with earlier age of onset, and may be harder to treat with classic cognitive-behavioral approaches to OCD. Of interest, sensory phenomena in OCD are associated with Tourette's syndrome and respond to pharmacological treatments primarily used for tics. As such, abnormal sensory processing may be a basic mechanism that links various psychiatric disorders.
The process of attending to body sensations is referred to as interoception, and broadly includes the detection of, or attention to, experiences arising from the viscera and soma. Research has revealed a cortical interoceptive circuit involving insula, anterior cingulate cortex (ACC), and somatomotor cortex.
Ondansetron (OND) is a good candidate for the modulation of the above-described interoceptive circuit. It is a selective 5-HT3 (serotonin) receptor antagonist that acts on both peripheral and central receptors. OND has long been used to treat nausea and vomiting due to chemotherapy, radiation therapy, anesthesia, and opioid-induced emesis. It has also been used alone or as adjunctive therapy for the treatment of both OCD and Tourette's disorder, showing some efficacy in small clinical trials. The mechanisms by which ondansetron improves symptoms in OCD and tic disorders are unknown, but a recent study found that OND application directly into the insula decreased disgust reactions in rats. This data suggests that ondansetron's clinical efficacy could be related to effects on interoceptive circuit activity in the insula and sensorimotor regions, a possibility that is being explored in the current protocol. Typical dosages for anti-emetic action is 8-24 mg. The investigator's pilot data found that a single 16 mg dose of ondansetron reduced activation of insula and somatosensory cortex in both healthy controls and patients with OCD. As a follow-up to this pilot work, the current protocol will compare the effects of three different dosages of ondansetron (8 mg, 16 mg, and 24 mg) on activation in insula and somatosensory cortex during tasks of cognition and perception in healthy adults.
- Conditions
- Brain Function, Healthy Adults
- Being tested
- ondansetron, placebo
- Keywords
- fMRI, Brain function, Sensory processing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ondansetronDrug
Also called Zofran
Ondansetron 8mg, 16mg, 24mg
placeboDrug
placebo pill
| Study group | Role | What they receive |
|---|---|---|
| ondansetron-8 | Experimental | Single dose of 8 mg ondansetron (crossover with single dose of placebo) Receives: Drug: ondansetron; Drug: placebo |
| ondansetron-16 | Experimental | Single dose of 16 mg ondansetron (crossover with single dose of placebo) Receives: Drug: ondansetron; Drug: placebo |
| ondansetron-24 | Experimental | Single dose of 24 mg ondansetron (crossover with single dose of placebo) Receives: Drug: ondansetron; Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD signal in the insula and somatosensory cortex measured by fMRI
On Day1, Functional magnetic resonance imaging (fMRI) will be done 90 minutes after drug or placebo ingestion to measure the blood oxygen level dependent (BOLD) signal in insula and somatosensory cortex.
Measured: Day 1
BOLD signal in the insula and somatosensory cortex measured by fMRI
At week 1, fMRI will be done 90 minutes after drug or placebo ingestion to measure the BOLD signal in insula and somatosensory cortex.
Measured: 1 week
Secondary outcomes (2)
BOLD signal in the whole brain measured by fMRI
On Day1, fMRI will be done 90 minutes after drug or placebo ingestion to measure the BOLD signal across the whole brain.
Measured: Day 1
BOLD signal in the whole brain measured by fMRI
At week 1, fMRI will be done 90 minutes after drug or placebo ingestion to measure the BOLD signal across the whole brain.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2015 (estimated)
- Study startAug 2015
- Primary completion3 Feb 2017
- Study completion3 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain FunctionStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Emily Stern, Icahn School of Medicine at Mount Sinai
- Investigators
- Emily Stern, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02460341
- Sponsor's protocol ID
- GCO 14-1794
- Status last verified
- Apr 2017
- First submitted
- 28 May 2015
- Last updated
- 11 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Ondansetron on Brain Function
- ClinicalTrials.gov ID
- NCT02460341
- Acronym / sponsor ID
- GCO 14-1794
- Conditions
- Brain Function, Healthy Adults
- Keywords
- fMRI, Brain function, Sensory processing
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- Aug 2015
- Primary completion
- 3 Feb 2017 (actual)
- Study completion
- 3 Feb 2017 (actual)
- First posted
- 2 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project investigates the effects of a single dose of ondansetron on brain function in healthy adults. The investigators hypothesize that there will be a dose-dependent reduction in activation of the insula and somatosensory brain regions associated with the use of ondansetron.
Detailed description
Objectives:
The overall objective of this study is to examine the effects of single doses of 8 mg, 16 mg, and 24 mg ondansetron as compared to placebo on neural mechanisms of cognition and perception in healthy individuals.
Background:
Many psychiatric disorders are associated with altered sensory experiences arising from within the body. Examples include increased experience of sensations or urges in muscles, skins, joints or visceral organs in tic disorders, OCD patients with symptoms of "not just right experiences" or disgust sensitivity, and impulse control disorders (ICDs) such as trichotillomania or skin-picking. In OCD, sensory phenomena occur in approximately half of patients, are associated with earlier age of onset, and may be harder to treat with classic cognitive-behavioral approaches to OCD. Of interest, sensory phenomena in OCD are associated with Tourette's syndrome and respond to pharmacological treatments primarily used for tics. As such, abnormal sensory processing may be a basic mechanism that links various psychiatric disorders.
The process of attending to body sensations is referred to as interoception, and broadly includes the detection of, or attention to, experiences arising from the viscera and soma. Research has revealed a cortical interoceptive circuit involving insula, anterior cingulate cortex (ACC), and somatomotor cortex.
Ondansetron (OND) is a good candidate for the modulation of the above-described interoceptive circuit. It is a selective 5-HT3 (serotonin) receptor antagonist that acts on both peripheral and central receptors. OND has long been used to treat nausea and vomiting due to chemotherapy, radiation therapy, anesthesia, and opioid-induced emesis. It has also been used alone or as adjunctive therapy for the treatment of both OCD and Tourette's disorder, showing some efficacy in small clinical trials. The mechanisms by which ondansetron improves symptoms in OCD and tic disorders are unknown, but a recent study found that OND application directly into the insula decreased disgust reactions in rats. This data suggests that ondansetron's clinical efficacy could be related to effects on interoceptive circuit activity in the insula and sensorimotor regions, a possibility that is being explored in the current protocol. Typical dosages for anti-emetic action is 8-24 mg. The investigator's pilot data found that a single 16 mg dose of ondansetron reduced activation of insula and somatosensory cortex in both healthy controls and patients with OCD. As a follow-up to this pilot work, the current protocol will compare the effects of three different dosages of ondansetron (8 mg, 16 mg, and 24 mg) on activation in insula and somatosensory cortex during tasks of cognition and perception in healthy adults.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ondansetron-8 | Experimental | Drug: ondansetron, Drug: placeboSingle dose of 8 mg ondansetron (crossover with single dose of placebo) |
| ondansetron-16 | Experimental | Drug: ondansetron, Drug: placeboSingle dose of 16 mg ondansetron (crossover with single dose of placebo) |
| ondansetron-24 | Experimental | Drug: ondansetron, Drug: placeboSingle dose of 24 mg ondansetron (crossover with single dose of placebo) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- All subjects must be medically healthy, between 18 and 60 years of age, and fluent (speaking and writing) in English
Key exclusion criteria (9 listed)
- Present or previous diagnosis of any psychiatric disorder or major developmental disorder (autism/Asperger's disorder, pervasive developmental disorder), based on psychiatric evaluation using the Mini International Neuropsychiatric Interview (M.I.N.I.) or Structured Clinical Interview for DSM disorders (SCID)
- Any disability or health problem that prevents them from completing study procedures (e.g. color blindness, severe carpal tunnel syndrome, etc.)
- History of organic mental syndromes, head trauma, migraines, seizures, other CNS neurological disease, recent use of illegal drugs or current substance dependence, or significant medical illness other than that listed above (by self-report)
- Pregnant or nursing women
- Subjects with a medical condition or other predisposition that increases the risk of adverse effects when taking ondansetron. These include individuals with drug allergies or known hypersensitivity to ondansetron (or other 5-HT3 antagonists), heart disease, congestive heart failure, heart rhythm disorder, congenital long QT syndrome, electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia) or hepatic impairment
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 |
|---|---|---|
| ondansetronAlso: ZofranOndansetron 8mg, 16mg, 24mg | Drug | ondansetron-16, ondansetron-24, ondansetron-8 |
| placeboplacebo pill | Drug | ondansetron-16, ondansetron-24, ondansetron-8 |
Primary outcome
BOLD signal in the insula and somatosensory cortex measured by fMRI
Time frame: Day 1
On Day1, Functional magnetic resonance imaging (fMRI) will be done 90 minutes after drug or placebo ingestion to measure the blood oxygen level dependent (BOLD) signal in insula and somatosensory cortex.
BOLD signal in the insula and somatosensory cortex measured by fMRI
Time frame: 1 week
At week 1, fMRI will be done 90 minutes after drug or placebo ingestion to measure the BOLD signal in insula and somatosensory cortex.
2 secondary outcomes
BOLD signal in the whole brain measured by fMRI
Time frame: Day 1
BOLD signal in the whole brain measured by fMRI
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2017.
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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.
Emily Stern, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ondansetron in people with Brain Function and Healthy Adults, run by Icahn School of Medicine at Mount Sinai 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 1 inclusion and 9 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 11 Apr 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
BOLD signal in the insula and somatosensory cortex measured by fMRI (time frame: Day 1). 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?
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 11 Apr 2017.