Obsessive-Compulsive Disorder, Tic Disorders, Tourette Syndrome
Conditions
Keywords
Brain Function, functional magnetic resonance imaging (fMRI), Sensory processing, Obsessive-Compulsive Disorder, OCD
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.
Interventions
DRUGOndansetron
5-HT3 (serotonin receptor type 3) antagonist commonly used to treat nausea and vomiting
DRUGPlacebo
placebo equivalent
Sponsors
National Institutes of Health (NIH)
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain Activation - Insula Cortex | Baseline, Week 4 | 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. |
| Change in Brain Activation - Somatosensory Cortex | Baseline, Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sensory Phenomena Scale (SPS) Score | Baseline, Week 4 | 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 | Baseline, Week 4 | 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 | Baseline, Week 4 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ondansetron (OND) 24 mg/day for 4 weeks
Ondansetron: 5-HT3 (serotonin receptor type 3) antagonist commonly used to treat nausea and vomiting | 27 |
| Placebo (PL) Placebo pill
Placebo: placebo equivalent | 24 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Withdrawal by subject (personal reasons) | 2 | 2 |
| Overall Study | Withdrawal by subject (reported medical side effects) | 2 | 1 |
Baseline characteristics
| Characteristic | Ondansetron (OND) | Total | Placebo (PL) |
|---|---|---|---|
| Age, Continuous | 31 years STANDARD_DEVIATION 9.96 | 30 years STANDARD_DEVIATION 11.16 | 29 years STANDARD_DEVIATION 12.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 41 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 41 Participants | 20 Participants |
| Region of Enrollment United States | 27 participants | 51 participants | 24 participants |
| Sex: Female, Male Female | 13 Participants | 27 Participants | 14 Participants |
| Sex: Female, Male Male | 14 Participants | 24 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 29 |
| other Total, other adverse events | 22 / 33 | 12 / 29 |
| serious Total, serious adverse events | 0 / 33 | 0 / 29 |
Outcome results
Primary
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.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ondansetron (OND) | Change in Brain Activation - Insula Cortex | -0.071 Parameter estimate of BOLD Signal Change | Standard Deviation 0.21 |
| Placebo (PL) | Change in Brain Activation - Insula Cortex | -0.0094 Parameter estimate of BOLD Signal Change | Standard Deviation 0.23 |
Primary
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.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ondansetron (OND) | Change in Brain Activation - Somatosensory Cortex | -0.097 Parameter estimate of BOLD Signal Change |
| Placebo (PL) | Change in Brain Activation - Somatosensory Cortex | -0.0052 Parameter estimate of BOLD Signal Change |
Secondary
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.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ondansetron (OND) | Change in Sensory Phenomena Scale (SPS) Score | 1.646 score on a scale | Standard Deviation 2.098 |
| Placebo (PL) | Change in Sensory Phenomena Scale (SPS) Score | 1.204 score on a scale | Standard Deviation 2.143 |
Secondary
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.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ondansetron (OND) | Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Score | 2.25 score on a scale |
| Placebo (PL) | Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Score | 1 score on a scale |
Secondary
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.
Time frame: Baseline, Week 4
Population: Sample is based on 10 patients with motor/phonic tic symptoms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ondansetron (OND) | Change in Yale Global Tic Severity Scale (YGTSS) Score | 1.4 score on a scale | Standard Deviation 2.97 |
| Placebo (PL) | Change in Yale Global Tic Severity Scale (YGTSS) Score | 3.6 score on a scale | Standard Deviation 6.99 |