Brief Title
Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
Official Title
Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
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.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Change in Sensory phenomena severity from baseline to 4 weeks
Secondary Outcome
Percent BOLD signal change
Condition
Obsessive-Compulsive Disorder
Intervention
Ondansetron
Study Arms / Comparison Groups
Ondansetron (OND)
Description: 24 mg/day for 4 weeks
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
60
Start Date
June 16, 2017
Completion Date
April 2022
Primary Completion Date
April 2022
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.
Gender
All
Ages
18 Years - 60 Years
Accepts Healthy Volunteers
No
Contacts
Emily Stern, PhD, 212-404-3919, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03239210
Organization ID
17-01608
Responsible Party
Sponsor
Study Sponsor
NYU Langone Health
Collaborators
National Institutes of Health (NIH)
Study Sponsor
Emily Stern, PhD, Principal Investigator, NYU Langone Health
Verification Date
July 2021