Clinical trial NCT04880278: Multimodal Assessment of Cannabinoid Target Engagement in Adults With Obsessive-Compulsive Disorder
Official title: Multimodal Assessment of Cannabinoid Target Engagement in Adults With Obsessive-Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Obsessive-Compulsive Disorder
Keywords: Nabilone
Fear Extinction
Threat Response
Goal-directed vs. Habitual Behavior
fMRI
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2021-05-10
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this research study is to test how a medication called nabilone (Cesamet) affects neurocognitive processes involved in obsessive-compulsive disorder (OCD), including threat response, processing of fear signals, and habitual behavior. OCD is a disabling illness that affects around 2% of the population and involves recurrent intrusive thoughts (obsessions) and repetitive behaviors (compulsions) that lead to distress and/or impaired functioning. Nabilone is a synthetic form of delta-9-tetrahydrocannabinol (THC, the primary psychoactive component of the cannabis plant). It acts on the brain's endocannabinoid system, which has been hypothesized to play a role in OCD symptoms. Nabilone is approved by the FDA for the treatment of chemotherapy-induced nausea and vomiting. It is not FDA-approved for treating OCD.

In this study, 60 adults with OCD will receive a single dose of either nabilone or placebo. Participants will then complete a series of assessments including neuroimaging, psychophysiology (e.g., skin conductance recording), computerized behavioral tasks, and self-report measures. The information gained from this study could contribute to the development of new treatments for people with OCD and related disorders.

Detailed description: The total time required for each participant is 4 visits, as outlined below:

Visit 1: Screening, Questionnaires, and Orientation: During this visit potential participants will learn about the study procedures, sign the informed consent documents, complete diagnostic evaluations and medical screening with study staff. Participants will also complete a series of forms that ask about demographic information, OCD symptoms, use of drugs and alcohol, and other aspects of physical and mental health.

Visit 2: Behavioral Tests: During this visit participants will complete several computer tasks. Study staff will measure reaction time and obtain psychophysiological information (e.g., skin conductance recordings). The tasks that the participant completes will involve viewing images within a virtual environment. An aversive stimulus (e.g., loud burst of noise, animated snake) may follow one image most of the time, while other images may never be followed by a noise or a snake. The participant will need to try to predict whether the aversive cue will occur or not based on which image is shown, and will be asked to repeatedly rate on a scale how likely they think it is that a noise/snake will occur after each image.

Visit 3: Behavioral Tests with Drug or Placebo and MRI scan: For safety reasons, participants will be asked not to take any drugs for at least 24 hours before this visit. They will also be asked not to use marijuana/cannabis for at least 2 weeks before participating. Participants will be required to test negative on a urine drug screen and breathalyzer before continuing with this visit; women must also have a negative pregnancy test. Participants will need to complete a field sobriety test at the end of this visit and will be asked not to drive or operate machinery for the following 24 hours; participants not traveling to the clinic by subway or taxi should arrange to have a friend or family member pick them up.

Two hours before beginning the Visit 3 tasks, participants will be asked to swallow a capsule containing either nabilone or placebo (sugar pill). Nabilone is a Food \& Drug Administration (FDA) approved medication, and the dose (1mg, one time) is unlikely to have any effects that last beyond the duration of the study visit. About every 30 minutes after taking the pill, the participant will fill out some questionnaires asking about how they are feeling at the moment. At the end of the session, they will also be asked to guess whether they received nabilone or placebo.

Participants will then complete a task that is similar to the one on the previous day (Visit 2), but will be completed in the MRI scanner. During the MRI scan, participants will view the same images as on the previous day (Visit 2), and may experience the same aversive stimulus as during Visit 2. They will again be asked to rate how much they expect to experience the aversive stimulus after each image and to self-report their level of anxiety on a scale from 0 to 100. Finally, they will be asked to relax with their eyes open while viewing a white fixation cross on a back background.

Participants will complete an additional task outside of the MRI scanner. Participants will be repeatedly asked to view and choose between different images (e.g., spaceships), which lead to a different set of images. They must select one image from this second set, with some choices leading to a small monetary reward.

Visit 4: Behavioral Tests and MRI scan: This visit will be very similar to Visit 3, except that participants will not receive any study medication. Participants will complete the same type of task inside the MRI scanner, while the study staff measures reaction time, psychophysiological response, and brain activation. Participants will view the same images as in Visits 2 and 3, and may experience the same aversive stimulus. Participants will again be asked to rate how much they expect to experience the aversive stimulus after each image and to report their level of anxiety on a scale from 0 to 100. Participants will again be asked to relax with their eyes open while viewing a white fixation cross on a black background. Finally, outside of the scanner, participants will complete another decision-making task similar to the one they completed the day before.

Eligibility criteria: Inclusion Criteria:

* Between 21-55 years of age
* Physically healthy and, if female, not pregnant
* Able to tolerate all study procedures
* Able to provide written informed consent to participate
* Right-handed
* Primary diagnosis of OCD
* Not taking psychotropic medications or other substances likely to interact with nabilone

Exclusion Criteria:

* History of any significant medical condition that may increase the risk of participation
* Females who are pregnant or nursing
* Current or lifetime history of psychiatric disorders other than OCD that may increase the risk of participation (e.g. lifetime psychosis or bipolar disorder)
* Current substance use disorder
* Positive urine toxicology or alcohol breathalyzer
* Any history of adverse reaction to a cannabinoid
* History of receiving cognitive behavior or exposure-based psychotherapy in the past 3 months
* History of ferrous-containing metals within the body (e.g., aneurysm clips, shrapnel/retained particles)
* History of claustrophobia or unable to tolerate confined spaces like an MRI

Primary outcomes:
measure: Brain Measure 1
timeFrame: 5 years
measure: Brain Measure 2
timeFrame: 5 years
measure: Skin conductance response (SCR)
timeFrame: 5 years
measure: Electromyography (EMG)
timeFrame: 5 years
measure: Expectancy Ratings
timeFrame: 5 years
Secondary outcomes:
measure: Two-step task performance
timeFrame: 5 years
measure: Subjective Units of Distress
timeFrame: 5 years
measure: Yale-Brown Obsessive-Compulsive Challenge Scale
timeFrame: Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.
measure: Spielberger State/Trait Anxiety Inventory (STAI)
timeFrame: Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.
measure: Visual Analog Scales (VAS)
timeFrame: Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.
measure: Nabilone Side Effects Checklist
timeFrame: Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.
measure: Drug Effects Questionnaire (DEQ)
timeFrame: Collected on Visit 3, immediately before capsule ingestion (Time 0), and 30, 60, 90, 120, 150, 180, and 240 minutes afterwards, as well as at 8 hours and 24 hours afterwards.
measure: End of Session Questionnaire (ESQ)
timeFrame: 5 years
measure: Heart rate
timeFrame: Heart rate will be collected at the following intervals during Visit 3: Immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.
measure: Blood pressure
timeFrame: Blood pressure will be collected at the following intervals during Visit 3: Immediately before capsule ingestion (Time 0), and 30, 60, 120, 180, and 240 minutes afterwards.
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: Columbia University/New York State Psychiatric Institute
name: Reilly Kayser, MD
role: PRINCIPAL_INVESTIGATOR
References: