Nabilone Use For Acute Pain in Inflammatory Bowel Disease Patients

Study Overview
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Brief Summary
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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: 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. 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
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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.

Official Title
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Nabilone Use for Acute Pain in Inflammatory Bowel Disease Patients With Chronic Opioid Use Undergoing Gastrointestinal Surgery: A Single-centered Randomized Controlled Trial

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Drug: Nabilone
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nabilone Treatment<br>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 | Drug: Nabilone<br>* Treatment regimen will involve nabilone capsule administration starting with 1mg BID orally first administered on POD #0. The patient will be continued on this medication for 72 hours<br>* Other names: Cesamet;|
| Placebo Comparator: Placebo Treatment<br>Patients who are chronic opioid users for chronic pain and have been exposed to cannabis or cannabinoid products, treated with IV PCA and placebo | Drug: Placebos<br>* Treatment regimen will involve placebo capsule administration, identical in colour, shape, size, taste and smell to the nabilone capsules, starting orally first administered on POD #0. The patient will be continued on this medication for 72 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total amount of opioid consumption postoperatively | All the narcotic consumption will be converted to IV morphine equivalents using standard conversation factors | For up to 72 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores at rest and movement | Based on visual analogue scale (VAS) scoring system (0-10), where score of 0 refers to no pain and a score of 10 refers to the worst pain imaginable | Starting from discharge from post-anesthetic care unit (PACU), twice a day for 72 hours | 
| Incidence of opioid related side effects | Based on Opioid-Related Symptom Distress Scale | Measured at 24, 48 and 72 hours | 
| Incidence of nabilone side effects at 24, 48, 72 hours | Including drowsiness, vertigo, blurred vision, sensation disturbance, dry mouth, ataxia, anorexia, asthenia, headache, orthostatic hypotension, seizure, syncope, confusion | Measured at 24, 48, 72 hours | 
| Ulcerative Colitis (UC) symptom severity | Based on Simple Clinical Colitis Activity Index (SCCAI) | Measured at baseline (pre-anesthetic clinic) and at 72 hrs | 
| Crohn disease (CD) symptom severity | Based on Harvey-Bradshaw Index (HBI) | Measured at baseline (pre-anesthetic clinic) and at 72 hrs | 
| Time to first flatus | The number of hours/days elapsed post-surgically when the patient has flatus | Assessed on a daily basis for occurrence of first flatus for up to 72 hrs | 
| Number of loose stools | Predominantly watery/non-formed stool. Bristol stool chart type 6 and 7 | Measured on a daily basis for up to 72 hrs after surgery | 
| Length of hospital stay | The total number of hours the patient is admitted in the hospital | Measured in hours, starting from arrival to post-anesthetic care unit (PACU) to the time of discharge from hospital for up to 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nabilone, Inflammatory Bowel Disease, Opioid