Δ9-THC (Namisol®) in Chronic Pancreatitis Patients Suffering From Persistent Abdominal Pain

• ClinicalTrials.gov Identifier: NCT01551511
• Recruitment Status: Completed
• First Posted: March 12, 2012
• Last Update Posted: October 28, 2014
• Sponsor: Radboud University Medical Center
• Collaborator: European Union
• Information provided by (Responsible Party): Radboud University Medical Center

Study Description

Brief Summary:

Abdominal pain resulting from chronic pancreatitis (CP) is often recurrent, intense and long-lasting, and is extremely difficult to treat. Medical analgesic therapy is considered as first choice in pain management of CP, resulting in regularly prescription of opioids. The adverse consequences of prolonged opioid use, including addiction, tolerance and opioid induced hyperalgesia, call for an alternative medical treatment. Cannabis has been used to treat pain for many centuries. Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive substance of the cannabis plant, has been shown in previous studies to be a promising analgesic. The development of Namisol®, a tablet containing purified Δ9-THC showing an improved pharmacokinetic profile, provides the opportunity to test the analgesic potential of Δ9-THC in favourable conditions. The current study aims to investigate the analgesic efficacy of Namisol® as add-on analgesic during a long-term treatment (52 days) of abdominal pain resulting from CP.

Condition or disease	Intervention/treatment	Phase
Pancreatitis, Chronic; Abdominal Pain; Chronic Pain	Drug: Tetrahydrocannabinol; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Δ9-THC (Namisol®) in Chronic Pancreatitis Patients Suffering From Persistent Abdominal Pain: a Randomized, Double-blinded, Placebo-controlled, Parallel Design
• Study Start Date: October 2012
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: June 2014

Arms and Interventions

Arm	Intervention/treatment
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
Placebo Comparator: Placebo	Drug: Placebo; Identical step-up approach to the Namisol arm.

Outcome Measures

Primary Outcome Measures :

1. Average VAS pain [ Time Frame: Baseline versus day 52 ]
   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 daily pain diary.

Secondary Outcome Measures :

1. EEG [ Time Frame: Baseline and day 52 ]
   Electroencephalogram; measuring evoked potentials to noxious electrical stimuli, evoked potentials to auditory stimuli (oddball), and FFT of spontaneous EEG.
2. QST [ Time Frame: Baseline versus day 15 and day 52 ]
   Quantitative Sensory Testing; measuring pressure pain thresholds, electrical thresholds, electric wind-up response, and DNIC.
3. Safety [ Time Frame: Baseline until follow-up (day 59-61) ]
   • Laboratory
   • ECG
   • HF / BP
   • Adverse events
4. Pharmacokinetics [ Time Frame: Predose levels at baseline, day 15 and day 52; postdose levels (30 min, 45 min, 60 min, 100 min) at day 15 and 52 ]
   THC, 11-OH-THC and THC-COOH concentrations
5. Functional parameters [ Time Frame: Baseline until day 52 ]
   • Body weight
   • Supplementary feeding
6. Quality of life [ Time Frame: Baseline versus day 52 ]
   Quality of life will be evaluated by questionnaires
7. Pharmacodynamics [ Time Frame: Baseline versus day 15 and day 52 ]
   Pharmacodynamics measured by body sway and questionnaires (VASBond & Lader and VASBowdle)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Aged 18 years or older
• Confirmed chronic pancreatitis
• 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:

• 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 32,0 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

Contacts and Locations

Locations

Netherlands

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands, 6500 HB

Sponsors and Collaborators

Radboud University Medical Center

European Union

Investigators

• Principal Investigator: Harry van Goor, MD PhD; Radboud University Nijmegen Medical Centre, department of surgery

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Radboud University Medical Center
• ClinicalTrials.gov Identifier: NCT01551511
• Other Study ID Numbers: HEEL-2011-02
• First Posted: March 12, 2012
• Last Update Posted: October 28, 2014
• Last Verified: October 2014

Keywords provided by Radboud University Medical Center:

chronic pancreatitis; abdominal pain; visceral pain; chronic pain

Additional relevant MeSH terms:

Pancreatitis; Pancreatitis, Chronic; Chronic Pain; Abdominal Pain; Pain; Neurologic Manifestations; Pancreatic Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Dronabinol; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists