Effects of Ondansetron in Obsessive-compulsive and Tic Disorders

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.

Study Overview

• Status: Completed
• Conditions: Obsessive-Compulsive Disorder; Tourette Syndrome; Tic Disorders
• Intervention / Treatment: Drug: Ondansetron; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine
    • New York, New York, United States, 10962
      • The Nathan S. Kline Institute for Psychiatric Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ondansetron (OND); 24 mg/day for 4 weeks	Drug: Ondansetron; 5-HT3 (serotonin receptor type 3) antagonist commonly used to treat nausea and vomiting; Other Names: Zofran
Placebo Comparator: Placebo (PL); Placebo pill	Drug: Placebo; placebo equivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain Activation - Insula Cortex	Change in brain activation is measured by parameter estimate of 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.	Baseline, Week 4
Change in Brain Activation - Somatosensory Cortex	Change in brain activation is measured by parameter estimate of 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.	Baseline, Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 4
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.	Baseline, Week 4
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.	Baseline, Week 4

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Emily Stern, PhD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2017
• Primary Completion (Actual): May 16, 2022
• Study Completion (Actual): May 16, 2022

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 3, 2017

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: OCD; Sensory processing; Obsessive-Compulsive Disorder; Brain Function; functional magnetic resonance imaging (fMRI)
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Personality Disorders; Anxiety Disorders; Dyskinesias; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Tourette Syndrome; Tic Disorders; Tics; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Ondansetron
• Other Study ID Numbers: 17-01608

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• 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