Clinical trial NCT03422861: Nabilone Use For Acute Pain in Inflammatory Bowel Disease Patients
Official title: Nabilone Use for Acute Pain in Inflammatory Bowel Disease Patients With Chronic Opioid Use Undergoing Gastrointestinal Surgery: A Single-centered Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Inflammatory Bowel Diseases
Keywords: Nabilone
Inflammatory Bowel Disease
Opioid
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
First posted: 2018-02-06
Enrollment: 80
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This is a clinical trial of nabilone for patients with Inflammatory Bowel Disease (IBD) who are undergoing IBD-related surgery (Any abdominal surgery lasting for more than one hour). This study would include a total of 80 patients undergoing general surgery who will have Intravenous Patient Controlled Analgesia (IVPCA) after surgery. It is the intention to randomize these patients postoperatively into 2 groups of 40 patients:

1. Patients who are chronic opioid users for chronic pain and have been exposed to cannabis or cannabinoid products, treated with IV PCA and nabilone as per protocol.
2. Patients who are chronic opioid users for chronic pain and have been exposed to cannabis or cannabinoid products, treated with IV PCA and placebo as per protocol.

The goal is two-fold. One is to demonstrate that patients will benefit from post-operative nabilone administration to achieve/maintain the opioid-sparing and pain modulation effects. Second is to demonstrate patients will benefit from the anti-inflammatory and immunomodulatory effects of nabilone to alleviate IBD symptoms and enhance recovery.

Detailed description: Patients generally have pre-anesthetic visits 1-2 weeks prior to their scheduled operation. Patients identified by the Clinical Research Study Assistant (CRSA) based on inclusion and exclusion criteria will be approached regarding this study in the pre-anesthetic clinic. Patients will be made aware of the components of the study and the CRSA will be present to answer any questions. Patients have until the day of the surgery after admission to the hospital (generally 4 hours before the planned procedure) to decide whether they want to be enrolled in this study. In most cases patients will have approximately 1-2 weeks from being made aware of this study to come to a decision. Even patients who have been scheduled for pre-anesthetic clinic visit less than 1 week prior to surgery will still have \>24 hrs to make decisions. Those admitted on the day of surgery may still be able to participate provided they have at least 4 hrs to review the study and have their questions answered by the study team. Patients will have access to a contact phone number in case they have additional questions. Baseline patient data will be collected once consent is obtained. On the day of surgery, administration of general anesthesia (GA) will be protocolized. Patients will cease their current oral opioid while on IV opioids. After the surgery, Patients will be randomly allocated into either placebo or intervention arm using a computerized random generator. Treatment regimen will involve nabilone capsule administration starting with 1mg twice a day orally first administered on post-operative day (POD) #0. The patient will be continued on this medication for 72 hours. Enrolled patients will document their pain scores and other data points as per study outcomes measured. The CRSA will follow for nabilone-related adverse effects at 24hrs, 48hrs, and 72hours post-operatively. Study subjects will also be followed up for psychotropic adverse reactions of nabilone (including hallucination, depressed mood, anxiety reactions, and euphoria) for 3 days after discontinuation of study treatment. This follow up will be made by the CRSA during the subject's stay in the hospital, or by telephone call made after discharge from the hospital. Any surgical complication will be recorded up to 30 days after the operation. The CRSA will administer study questionnaires and assist patients in their completion. The CRSA will work with the principal investigator (PI) to capture all requirements for study evaluation.

Eligibility criteria: Inclusion Criteria:

* Age≥25 years
* Be able to understand the study procedures
* Voluntarily provide written informed consent
* Be planned to undergo abdominal surgery related to IBD lasting more than an hour
* previously and safely tolerated side effects of nabilone use
* Chronic opioid users who are defined as opioid consumption of 20mg oral morphine equivalent per day for \> 3 months
* Negative pregnancy test for females of child bearing potential and they should use acceptable birth controlling measures such as barriers, Intra Uterine Devices (IUDs) or Hormonal contraceptives consistently and correctly for one month post last dose of study drug
* Male participants must also agree to consent and correct use of acceptable contraception during and for 3 months post last dose of study drug and agree not to donate sperm during this time period (90 days)

Exclusion Criteria:

* Age under 25
* Are allergic or hypersensitive to cannabis or any cannabinoid-Have severe liver( Acute hepatitis or CHILD Score ≥2), kidney, heart (any acute condition, decompensated Heart failure or Metabolic equivalent of task(MET) \< 4) or lung disease
* Have a personal or family history of serious psychotic disorders such as schizophrenia or psychosis
* Are pregnant, or are planning to get pregnant, or are breast feeding
* Are a man who wishes to start a family during duration of trial
* Have a history of alcohol or substance use disorders, including: hallucinogens (phencyclidine or similarly acting arylcyclohexylamines), other hallucinogens such as LSD, inhalants, sedatives, hypnotics, anxiolytics, and stimulants (including amphetamine-type substances, cocaine, and other stimulants).
* History of hypertension on medication
* Clinically significant lactose intolerant
* Nabilone treatment within the past month before surgery
* Diazepam or secobarbital use before surgery
* Hypersensitivity to Cesamet or any of its excipients
* Elderly (\>65 years)
* History of emotional disorders

Primary outcomes:
measure: Total amount of opioid consumption postoperatively
timeFrame: For up to 72 hours after surgery
Secondary outcomes:
measure: Pain scores at rest and movement
timeFrame: Starting from discharge from post-anesthetic care unit (PACU), twice a day for 72 hours
measure: Incidence of opioid related side effects
timeFrame: Measured at 24, 48 and 72 hours
measure: Incidence of nabilone side effects at 24, 48, 72 hours
timeFrame: Measured at 24, 48, 72 hours
measure: Ulcerative Colitis (UC) symptom severity
timeFrame: Measured at baseline (pre-anesthetic clinic) and at 72 hrs
measure: Crohn disease (CD) symptom severity
timeFrame: Measured at baseline (pre-anesthetic clinic) and at 72 hrs
measure: Time to first flatus
timeFrame: Assessed on a daily basis for occurrence of first flatus for up to 72 hrs
measure: Number of loose stools
timeFrame: Measured on a daily basis for up to 72 hrs after surgery
measure: Length of hospital stay
timeFrame: Measured in hours, starting from arrival to post-anesthetic care unit (PACU) to the time of discharge from hospital for up to 10 days
Other outcomes:
measure: Patients' Global Impression of Change (PGIC)
timeFrame: Measured at baseline and 72 hours
measure: Incidence of depression
timeFrame: Measured at baseline, 24, 48 and 72 hours and also for 72 hours after discontinuation of study treatment
measure: Incidence of psychotropic adverse reactions of Nabilone using a questionnaire
timeFrame: Measured for 72 hours after discontinuation of trial treatment
measure: Incidence of suicide
timeFrame: For 72 hours after discontinuation of trial treatment
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: Mount Sinai Hospital Department of Anesthesia and Pain Management
name: Naveed Siddiqui, M.D
role: PRINCIPAL_INVESTIGATOR
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