The Analgesic Efficacy of Δ9-THC (Namisol®) in Patients With Persistent Postsurgical Abdominal Pain

The Analgesic Efficacy of Δ9-THC (Namisol®) in Patients With Persistent Postsurgical Abdominal Pain; a Randomized, Double Blinded, Placebo-controlled, Experiment

Persistent postsurgical abdominal pain (PPAP) is a very difficult to treat pain. This pain can persist for months or even years and significantly diminishes quality of life. The exact underlying cause for this pain persistence is still unclear, which makes its treatment still a challenge. The promising analgesic effects of Δ9-THC in previous research, plus the improved bioavailability of Namisol® in comparison with previous Δ9-THC substances form the basis of the present research proposal.

The current study aims to investigate the analgesic efficacy of Namisol® as add-on analgesic during a long-term treatment (52 days) of persistent postsurgical abdominal pain.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Abdominal Pain; Postsurgical Pain
• Intervention / Treatment: Drug: Tetrahydrocannabinol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • Radboud University Nijmegen Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 years or older
• Pain should have developed after a surgical procedure
• Pain duration exceeding 3 months, and average NRS≥3
• Stable doses intake of analgesics for the past 2 months
• The patient has been informed about the study, understood the information and signed the informed consent form

Exclusion Criteria:

• Diagnosed irritated bowel syndrome (IBS) or chronic pancreatitis
• Patient took cannabinoids on a regular basis for at least one year
• Patient does not feel a pinprick test in the lower extremities
• Patient has a body mass index (BMI) above 36,0 kg/m2
• Patient suffers from serious painful conditions other than chronic pancreatitis
• Patient has a significant medical disorder that may interfere with the study or may pose a risk for the patient
• Patient uses any kind of concomitant medication that may interfere with the study or may pose a risk for the patient
• Patient does not tolerate oral intake of medication or liquids, or is refrained from oral intake because of medical reasons
• Patient demonstrates clinical relevant deviations in the electrocardiogram (ECG)
• Patient has an actual moderate to severe renal impairment
• Patient has an actual moderate to severe hepatic impairment
• Patient has a presence or history of major psychiatric illness
• Patient has experienced an epileptic seizure in the past
• Patient demonstrates clinically significant laboratory abnormalities
• Patient demonstrates a positive urine drug screen for THC, cocaine, MDMA, and amphetamines
• Patient demonstrates a positive test result on hepatitis B surface antigen, hepatitis C antibody or HIV antibody test
• Patient has a history of sensitivity / idiosyncrasy to THC
• Patient has a known or suspected lactose intolerance
• Female patient is pregnant or breastfeeding
• Patient intends to conceive a child during the course of the study
• Patient participates in another investigational drug study
• Patient has a clinical significant exacerbation in illness
• Patient is unwilling or unable to comply with the lifestyle guidelines

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Identical to the Namisol arm.
EXPERIMENTAL: delta-9-tetrahydrocannabinol (namisol)	Drug: Tetrahydrocannabinol; The add-on treatment consists of two phases: a step-up phase (day 1-5: 3 mg TID; day 6-10: 5 mg TID), and a stable dose phase (day 11-52: 8 mg TID). The dosage may be tapered to at least 5 mg TID, when 8 mg is not tolerated.; Other Names: Namisol; Dronabinol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average VAS pain	The primary outcome measure is defined as the reduction in average VAS pain scores at the end of the study (day 50-52) compared to the pre-treatment level between the Namisol® and placebo group, measured by a Visual Analoge Scale (VAS) in a pain diary.	Baseline versus day 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	Quality of life will be evaluated by questionnaires	Baseline versus day 52
Electroencephalogram (EEG)	Evoked potentials to noxious electrical stimuli, evoked potentials to auditory stimuli (oddball), and spontaneous brain activity will be measured in the electroencephalogram (EEG).	Baseline versus day 52
Quantitative Sensory Testing (QST)	Pressure pain thresholds, electrical thresholds, electric wind-up response, and Diffuse Noxious Inhibitory Control (DNIC) will be measured using Quantitative Sensory Testing (QST).	Baseline versus day 15 and day 52
Depression and (pain related) anxiety	Depression and (pain related) anxiety measured by questionnaires.	Baseline versus day 52
Pharmacodynamic parameters	Pharmacodynamics measured by body sway and questionnaires (VASBond & Lader and VASBowdle)	Baseline versus day 15 and day 52
Safety parameters	Laboratory; Electrocardiogram (ECG); Heart Frequency (HF) / Blood Pressure (BP); Adverse Events (AE)	Baseline until follow-up (day 59-61)

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: European Union
• Investigators: Principal Investigator: Harry van Goor, MD, PhD, Radboud University Nijmegen Medical Centre, department of surgery

Publications and helpful links

General Publications

• de Vries M, van Rijckevorsel DCM, Vissers KCP, Wilder-Smith OHG, van Goor H; Pain and Nociception Neuroscience Research Group. Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study. Clin Gastroenterol Hepatol. 2017 Jul;15(7):1079-1086.e4. doi: 10.1016/j.cgh.2016.09.147. Epub 2016 Oct 5.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: March 7, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (ESTIMATE): March 23, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 28, 2014
• Last Update Submitted That Met QC Criteria: October 27, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: chronic pain; visceral pain; abdominal pain; postsurgical pain
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Pain, Postoperative; Chronic Pain; Abdominal Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: HEEL-2011-03