Effects of Ondansetron in Obsessive-compulsive and Tic Disorders

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 Status

Drug

Estimated Enrollment

110

Start Date

June 16, 2017

Completion Date

May 16, 2022

Primary Completion Date

May 16, 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, , 

Location Countries

United States

Location Countries

United States

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

August 2022