Nabilone Use For Acute Pain in Inflammatory Bowel Disease Patients

NCT03422861 | Unknown

• 1 other identifier: NAB-2017
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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. 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. 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.

Conditions

Inflammatory Bowel Diseases

Keywords

Nabilone; Inflammatory Bowel Disease; Opioid

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Pain scores at rest and movement

  Starting from discharge from post-anesthetic care unit (PACU), twice a day for 72 hours

• Incidence of opioid related side effects

  Measured at 24, 48 and 72 hours

• Incidence of nabilone side effects at 24, 48, 72 hours

  Measured at 24, 48, 72 hours

• Ulcerative Colitis (UC) symptom severity

  Measured at baseline (pre-anesthetic clinic) and at 72 hrs

• Crohn disease (CD) symptom severity

  Measured at baseline (pre-anesthetic clinic) and at 72 hrs

Other Outcomes (4)

• Patients' Global Impression of Change (PGIC)

  Measured at baseline and 72 hours

• Incidence of depression

  Measured at baseline, 24, 48 and 72 hours and also for 72 hours after discontinuation of study treatment

• Incidence of psychotropic adverse reactions of Nabilone using a questionnaire

  Measured for 72 hours after discontinuation of trial treatment

Study Arms (2)

Nabilone Treatment

ACTIVE COMPARATOR

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

Placebo Treatment

PLACEBO COMPARATOR

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

Interventions

Nabilone DRUG

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

Also known as: Cesamet

Nabilone Treatment

Placebos DRUG

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

Placebo Treatment

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Related Publications (21)

• Lal S, Prasad N, Ryan M, Tangri S, Silverberg MS, Gordon A, Steinhart H. Cannabis use amongst patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011 Oct;23(10):891-6. doi: 10.1097/MEG.0b013e328349bb4c.

  PMID: 21795981 RESULT

• Di Sabatino A, Battista N, Biancheri P, Rapino C, Rovedatti L, Astarita G, Vanoli A, Dainese E, Guerci M, Piomelli D, Pender SL, MacDonald TT, Maccarrone M, Corazza GR. The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease. Mucosal Immunol. 2011 Sep;4(5):574-83. doi: 10.1038/mi.2011.18. Epub 2011 Apr 6.

  PMID: 21471961 RESULT

• Singh UP, Singh NP, Singh B, Price RL, Nagarkatti M, Nagarkatti PS. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10(-/-) mice by attenuating the activation of T cells and promoting their apoptosis. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):256-67. doi: 10.1016/j.taap.2011.11.005. Epub 2011 Nov 18.

  PMID: 22119709 RESULT

• Izzo AA, Sharkey KA. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther. 2010 Apr;126(1):21-38. doi: 10.1016/j.pharmthera.2009.12.005. Epub 2010 Feb 1.

  PMID: 20117132 RESULT

• Alhouayek M, Muccioli GG. The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends Mol Med. 2012 Oct;18(10):615-25. doi: 10.1016/j.molmed.2012.07.009. Epub 2012 Aug 21.

  PMID: 22917662 RESULT

• Naftali T, Lev LB, Yablecovitch D, Half E, Konikoff FM. Treatment of Crohn's disease with cannabis: an observational study. Isr Med Assoc J. 2011 Aug;13(8):455-8.

  PMID: 21910367 RESULT

• Lahat A, Lang A, Ben-Horin S. Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot prospective study. Digestion. 2012;85(1):1-8. doi: 10.1159/000332079. Epub 2011 Nov 17.

  PMID: 22095142 RESULT

• Naftali T, Bar-Lev Schleider L, Dotan I, Lansky EP, Sklerovsky Benjaminov F, Konikoff FM. Cannabis induces a clinical response in patients with Crohn's disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol. 2013 Oct;11(10):1276-1280.e1. doi: 10.1016/j.cgh.2013.04.034. Epub 2013 May 4.

  PMID: 23648372 RESULT

• Kelly S, Jhaveri MD, Sagar DR, Kendall DA, Chapman V. Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation. Eur J Neurosci. 2003 Oct;18(8):2239-43. doi: 10.1046/j.1460-9568.2003.02957.x.

  PMID: 14622184 RESULT

• Ibrahim MM, Rude ML, Stagg NJ, Mata HP, Lai J, Vanderah TW, Porreca F, Buckley NE, Makriyannis A, Malan TP Jr. CB2 cannabinoid receptor mediation of antinociception. Pain. 2006 May;122(1-2):36-42. doi: 10.1016/j.pain.2005.12.018. Epub 2006 Mar 23.

  PMID: 16563625 RESULT

• Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73. doi: 10.1001/jama.2015.6358.

  PMID: 26103030 RESULT

• Salio C, Fischer J, Franzoni MF, Mackie K, Kaneko T, Conrath M. CB1-cannabinoid and mu-opioid receptor co-localization on postsynaptic target in the rat dorsal horn. Neuroreport. 2001 Dec 4;12(17):3689-92. doi: 10.1097/00001756-200112040-00017.

  PMID: 11726775 RESULT

• Smith PA, Selley DE, Sim-Selley LJ, Welch SP. Low dose combination of morphine and delta9-tetrahydrocannabinol circumvents antinociceptive tolerance and apparent desensitization of receptors. Eur J Pharmacol. 2007 Oct 1;571(2-3):129-37. doi: 10.1016/j.ejphar.2007.06.001. Epub 2007 Jun 12.

  PMID: 17603035 RESULT

• Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011 Dec;90(6):844-51. doi: 10.1038/clpt.2011.188. Epub 2011 Nov 2.

  PMID: 22048225 RESULT

• Beaulieu P. Effects of nabilone, a synthetic cannabinoid, on postoperative pain. Can J Anaesth. 2006 Aug;53(8):769-75. doi: 10.1007/BF03022793.

  PMID: 16873343 RESULT

• Buggy DJ, Toogood L, Maric S, Sharpe P, Lambert DG, Rowbotham DJ. Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. Pain. 2003 Nov;106(1-2):169-72. doi: 10.1016/s0304-3959(03)00331-2.

  PMID: 14581124 RESULT

• Holdcroft A, Maze M, Dore C, Tebbs S, Thompson S. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management. Anesthesiology. 2006 May;104(5):1040-6. doi: 10.1097/00000542-200605000-00021.

  PMID: 16645457 RESULT

• Jain AK, Ryan JR, McMahon FG, Smith G. Evaluation of intramuscular levonantradol and placebo in acute postoperative pain. J Clin Pharmacol. 1981 Aug-Sep;21(S1):320S-326S. doi: 10.1002/j.1552-4604.1981.tb02610.x.

  PMID: 7028791 RESULT

• Von Korff M, Saunders K, Thomas Ray G, Boudreau D, Campbell C, Merrill J, Sullivan MD, Rutter CM, Silverberg MJ, Banta-Green C, Weisner C. De facto long-term opioid therapy for noncancer pain. Clin J Pain. 2008 Jul-Aug;24(6):521-7. doi: 10.1097/AJP.0b013e318169d03b.

  PMID: 18574361 RESULT

• Toth C, Mawani S, Brady S, Chan C, Liu C, Mehina E, Garven A, Bestard J, Korngut L. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain. 2012 Oct;153(10):2073-2082. doi: 10.1016/j.pain.2012.06.024. Epub 2012 Aug 23.

  PMID: 22921260 RESULT

• Turcotte D, Doupe M, Torabi M, Gomori A, Ethans K, Esfahani F, Galloway K, Namaka M. Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial. Pain Med. 2015 Jan;16(1):149-59. doi: 10.1111/pme.12569. Epub 2014 Oct 7.

  PMID: 25288189 RESULT

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

nabilone

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Naveed Siddiqui, M.D

  Mount Sinai Hospital Department of Anesthesia and Pain Management

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Naveed Siddiqui, M.D

CONTACT

416-586-4800; naveed.siddiqui@uhn.com

Zeev Friedman, M.D

CONTACT

zeev.friedman@sinaihealthsystem.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 15, 2018
• First Posted: February 6, 2018
• Study Start: December 1, 2023
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: June 7, 2023

Record last verified: 2023-06

Locations

CA (1)