Back to resultsEffects of Ondansetron in Obsessive-compulsive and Tic Disorders
Primary Purpose
Obsessive-Compulsive Disorder, Tic Disorders, Tourette Syndrome
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ondansetron
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obsessive-Compulsive Disorder focused on measuring Brain Function, functional magnetic resonance imaging (fMRI), Sensory processing, Obsessive-Compulsive Disorder, OCD
Eligibility Criteria
Inclusion Criteria:
- Patients must be medically healthy, between 18 and 60 years of age
- Fluent (speaking and writing) in English
- Patients must have a current diagnosis of obsessive-compulsive disorder (OCD) or tic disorder (OCD) according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria with moderate or greater disorder severity and moderate or greater severity of sensory phenomena
- Patients must be unmedicated or taking antidepressants, stable for at least 6 weeks
Exclusion Criteria:
- Present or previous diagnosis of any psychosis, bipolar disorder, or major developmental disorder (autism/Asperger's disorder, pervasive developmental disorder). Present diagnosis of alcohol or substance use disorder (moderate or severe) will also be exclusionary.
- 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 central nervous system (CNS) neurological disease, or significant medical illness other than that listed above.
- Pregnant or nursing women will be excluded.
- Subjects with a medical condition or other predisposition that increases the risk of adverse effects when taking ondansetron. These include, but are not limited to, 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.
- 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.
Sites / Locations
- New York University School of Medicine
- The Nathan S. Kline Institute for Psychiatric Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Ondansetron (OND)
Placebo (PL)
Arm Description
24 mg/day for 4 weeks
Placebo pill
Outcomes
Primary Outcome Measures
Change in Brain Activation - Insula Cortex
Change in brain activation is measured by percentage blood-oxygen-level dependent (BOLD) signal change in the insula cortex. BOLD signal is captured via functional MRI taken during MRI scanning sessions. Participants viewed "body-focused" videos (e.g., close-ups of a brush stroking a hand) alternating with control videos depicting similar types of movements but without body parts (e.g., a pen moving across a table) in an MRI scanner. Analysis examined change in brain activation between baseline and final during the viewing of body-focused videos compared to control videos. The outcome measure is the change in brain activation (Baseline minus Final) averaged across the right and left insula regions of interest.
Change in Brain Activation - Somatosensory Cortex
Change in brain activation is measured by percentage blood-oxygen-level dependent (BOLD) signal change in the somatosensory cortex. BOLD signal is captured via functional MRI taken during MRI scanning sessions. Participants viewed "body-focused" videos (e.g., close-ups of a brush stroking a hand) alternating with control videos depicting similar types of movements but without body parts (e.g., a pen moving across a table) in an MRI scanner. Analysis examined change in brain activation between baseline and final during the viewing of body-focused videos compared to control videos. The outcome measure is the change in brain activation (Baseline minus Final) averaged across the right and left postcentral gyrus regions of interest.
Secondary Outcome Measures
Change in Sensory Phenomena Scale (SPS) Score
The SPS is a clinician-rated scale that assesses presence or absence of sensory phenomena. It contains a checklist with examples of different types of sensory phenomena, including physical sensations, "just right" sensations, incompleteness, general energy or inner tension buildup, and urges. The total score ranges from 0-15, with higher scores indicating more severe sensory phenomena. A score of 6 or more is defined as moderate or greater severity of sensory phenomena. An decrease in scores indicates severity decreased during the observational period.
Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Score
Y-BOCS is designed to rate the severity and type of symptoms in patients with obsessive compulsive disorder. In general, the items depend on the patient's report; however, the final rating is based on the clinical judgement of the interviewer. The scale consists of 10 items summed to determine the level of symptom severity. The total score ranges from 0 to 40 with higher scores indicating greater symptom severity. A decrease in scores indicates symptom severity decreased during the observational period.
Change in Yale Global Tic Severity Scale (YGTSS) Score
The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The total score is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity. A decrease in scores indicates severity decreased during the observational period.
Full Information
NCT ID
NCT03239210
First Posted
August 1, 2017
Last Updated
June 13, 2023
Sponsor
NYU Langone Health
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT03239210
Brief Title
Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
Official Title
Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
June 16, 2017 (Actual)
Primary Completion Date
May 16, 2022 (Actual)
Study Completion Date
May 16, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
National Institutes of Health (NIH)
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This project investigates the use of 4 weeks of 24 mg/day ondansetron as compared to placebo on symptoms and brain functioning in patients with obsessive-compulsive disorder (OCD) and tic disorders (TD). Patients will be randomized to receive ondansetron or placebo for 4 weeks, with MRI scans and symptom assessments occurring at baseline (before any drug) and at the end of the 4 weeks. Patients will also be asked to come into the lab approximately 2 weeks into the trial for symptom assessments. The investigators hypothesize that after 4 weeks there will be greater reduction from baseline in sensory symptoms and the activation of the insula and sensorimotor cortex compared for ondansetron as compared to placebo.
Detailed Description
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/Tourette's Disorders, OCD patients with symptoms of "not just right experiences" or disgust sensitivity, and other disorders such as trichotillomania or excoriation disorder. In OCD, these 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, abnormality of which may be related to sensory phenomena. Research has revealed a cortical interoceptive circuit involving insula, anterior cingulate cortex (ACC), and sensorimotor 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, although the investigator's earlier study found that single doses of ondansetron reduce activation of insula and somatosensory cortex in healthy controls. As a follow-up to this work, the current protocol will compare the effects of 24 mg/day of ondansetron vs. placebo for 4 weeks in patients with OCD or Tic Disorders on symptoms and brain functioning.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obsessive-Compulsive Disorder, Tic Disorders, Tourette Syndrome
Keywords
Brain Function, functional magnetic resonance imaging (fMRI), Sensory processing, Obsessive-Compulsive Disorder, OCD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
110 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ondansetron (OND)
Arm Type
Active Comparator
Arm Description
24 mg/day for 4 weeks
Arm Title
Placebo (PL)
Arm Type
Placebo Comparator
Arm Description
Placebo pill
Intervention Type
Drug
Intervention Name(s)
Ondansetron
Other Intervention Name(s)
Zofran
Intervention Description
5-HT3 (serotonin receptor type 3) antagonist commonly used to treat nausea and vomiting
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo equivalent
Primary Outcome Measure Information:
Title
Change in Brain Activation - Insula Cortex
Description
Change in brain activation is measured by percentage blood-oxygen-level dependent (BOLD) signal change in the insula cortex. BOLD signal is captured via functional MRI taken during MRI scanning sessions. Participants viewed "body-focused" videos (e.g., close-ups of a brush stroking a hand) alternating with control videos depicting similar types of movements but without body parts (e.g., a pen moving across a table) in an MRI scanner. Analysis examined change in brain activation between baseline and final during the viewing of body-focused videos compared to control videos. The outcome measure is the change in brain activation (Baseline minus Final) averaged across the right and left insula regions of interest.
Time Frame
Baseline, Week 4
Title
Change in Brain Activation - Somatosensory Cortex
Description
Change in brain activation is measured by percentage blood-oxygen-level dependent (BOLD) signal change in the somatosensory cortex. BOLD signal is captured via functional MRI taken during MRI scanning sessions. Participants viewed "body-focused" videos (e.g., close-ups of a brush stroking a hand) alternating with control videos depicting similar types of movements but without body parts (e.g., a pen moving across a table) in an MRI scanner. Analysis examined change in brain activation between baseline and final during the viewing of body-focused videos compared to control videos. The outcome measure is the change in brain activation (Baseline minus Final) averaged across the right and left postcentral gyrus regions of interest.
Time Frame
Baseline, Week 4
Secondary Outcome Measure Information:
Title
Change in Sensory Phenomena Scale (SPS) Score
Description
The SPS is a clinician-rated scale that assesses presence or absence of sensory phenomena. It contains a checklist with examples of different types of sensory phenomena, including physical sensations, "just right" sensations, incompleteness, general energy or inner tension buildup, and urges. The total score ranges from 0-15, with higher scores indicating more severe sensory phenomena. A score of 6 or more is defined as moderate or greater severity of sensory phenomena. An decrease in scores indicates severity decreased during the observational period.
Time Frame
Baseline, Week 4
Title
Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Score
Description
Y-BOCS is designed to rate the severity and type of symptoms in patients with obsessive compulsive disorder. In general, the items depend on the patient's report; however, the final rating is based on the clinical judgement of the interviewer. The scale consists of 10 items summed to determine the level of symptom severity. The total score ranges from 0 to 40 with higher scores indicating greater symptom severity. A decrease in scores indicates symptom severity decreased during the observational period.
Time Frame
Baseline, Week 4
Title
Change in Yale Global Tic Severity Scale (YGTSS) Score
Description
The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The total score is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity. A decrease in scores indicates severity decreased during the observational period.
Time Frame
Baseline, Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must be medically healthy, between 18 and 60 years of age
Fluent (speaking and writing) in English
Patients must have a current diagnosis of obsessive-compulsive disorder (OCD) or tic disorder (OCD) according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria with moderate or greater disorder severity and moderate or greater severity of sensory phenomena
Patients must be unmedicated or taking antidepressants, stable for at least 6 weeks
Exclusion Criteria:
Present or previous diagnosis of any psychosis, bipolar disorder, or major developmental disorder (autism/Asperger's disorder, pervasive developmental disorder). Present diagnosis of alcohol or substance use disorder (moderate or severe) will also be exclusionary.
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 central nervous system (CNS) neurological disease, or significant medical illness other than that listed above.
Pregnant or nursing women will be excluded.
Subjects with a medical condition or other predisposition that increases the risk of adverse effects when taking ondansetron. These include, but are not limited to, 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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emily Stern, PhD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
The Nathan S. Kline Institute for Psychiatric Research
City
New York
State/Province
New York
ZIP/Postal Code
10962
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data Sharing Plan The project will be registered and results reported on ClinicalTrials.gov. Neuroimaging data and associated files (e.g. behavioral response data generated during tasks) will be de-identified and provided for use by other researchers. De-identification will include removal of sensitive data from image file headers (e.g. name, date of birth). The anonymized final data set will be made available upon request, with an announcement on the lab website providing information on how to obtain the data. In addition, final data will be uploaded to an appropriate public database, such as the Open fMRI project, for broad availability. Data sharing will comply with local, state, and federal laws and regulations, including the Health Insurance Portability and Accountability Act (HIPAA), as well as institutional policies and review
IPD Sharing Time Frame
Data will be made available when the study team has published the outcomes of our primary and secondary analyses.
IPD Sharing Access Criteria
A written request must be made to the PI for access to the data. This request will involve providing an abstract detailing the planned analyses and utilization of the data and a signed agreement not to share the data with any other person.
Learn more about this trial
Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
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