Effects of Ondansetron in Obsessive-compulsive and Tic Disorders

Sponsor

NYU Langone Health (Other)

Overall Status

Completed

CT.gov ID

NCT03239210

Collaborator

National Institutes of Health (NIH) (NIH)

110

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Obsessive-Compulsive Disorder Tic Disorders Tourette Syndrome	Drug: Ondansetron Drug: Placebo	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effects of Ondansetron in Obsessive-compulsive and Tic Disorders

Actual Study Start Date :

Jun 16, 2017

Actual Primary Completion Date :

May 16, 2022

Actual Study Completion Date :

May 16, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in Sensory phenomena severity from baseline to 4 weeks [baseline and 4 weeks]
Sensory phenomena scale, Minimum: 0, Maximum: 15, higher scores indicate more severe sensory phenomena

Secondary Outcome Measures

Percent BOLD signal change [baseline and 4 weeks]
Change in brain activation as measured by % blood-oxygen-level dependent (BOLD) signal change in insula and sensorimotor cortex from baseline to 4 weeks
Patient-Related Inventory of Side effects [baseline and 4 weeks]
Using the Patient-Rated Inventory of Side effects, greater endorsement indicates more side effects

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York University School of Medicine	New York	New York	United States	10016
2	The Nathan S. Kline Institute for Psychiatric Research	New York	New York	United States	10962