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

Chronic Pain Clinical Trial

Official title:

Δ9-THC (Namisol®) in Chronic Pancreatitis Patients Suffering From Persistent Abdominal Pain: a Randomized, Double-blinded, Placebo-controlled, Parallel Design

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01551511
• Other study ID #: HEEL-2011-02
• Status: Completed
• Phase: Phase 2
• First received: February 7, 2012
• Last updated: October 27, 2014
• Start date: October 2012
• Est. completion date: June 2014

Study information

• Verified date: October 2014
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abdominal Pain
• Chronic Pain
• Pancreatitis
• Pancreatitis, Chronic

Intervention

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.
• Placebo
Identical step-up approach to the Namisol arm.

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	European Union

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 daily pain diary.	Baseline versus day 52	No
Secondary	EEG	Electroencephalogram; measuring evoked potentials to noxious electrical stimuli, evoked potentials to auditory stimuli (oddball), and FFT of spontaneous EEG.	Baseline and day 52	No
Secondary	QST	Quantitative Sensory Testing; measuring pressure pain thresholds, electrical thresholds, electric wind-up response, and DNIC.	Baseline versus day 15 and day 52	No
Secondary	Safety	Laboratory; ECG; HF / BP; Adverse events	Baseline until follow-up (day 59-61)	Yes
Secondary	Pharmacokinetics	THC, 11-OH-THC and THC-COOH concentrations	Predose levels at baseline, day 15 and day 52; postdose levels (30 min, 45 min, 60 min, 100 min) at day 15 and 52	No
Secondary	Functional parameters	Body weight; Supplementary feeding	Baseline until day 52	No
Secondary	Quality of life	Quality of life will be evaluated by questionnaires	Baseline versus day 52	No
Secondary	Pharmacodynamics	Pharmacodynamics measured by body sway and questionnaires (VASBond & Lader and VASBowdle)	Baseline versus day 15 and day 52	No