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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pancreatitis, Chronic, Abdominal Pain, Chronic Pain

Intervention / Treatment
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* Drug: Tetrahydrocannabinol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: delta-9-tetrahydrocannabinol (namisol)<br> | Drug: Tetrahydrocannabinol<br>* 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.<br>* Other names: Dronabinol;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Identical step-up approach to the Namisol arm.<br>|

What is the study measuring?
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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 daily pain diary. | Baseline versus day 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EEG | Electroencephalogram; measuring evoked potentials to noxious electrical stimuli, evoked potentials to auditory stimuli (oddball), and FFT of spontaneous EEG. | Baseline and day 52 | 
| QST | Quantitative Sensory Testing; measuring pressure pain thresholds, electrical thresholds, electric wind-up response, and DNIC. | Baseline versus day 15 and day 52 | 
| Safety | Laboratory ECG HF / BP Adverse events | Baseline until follow-up (day 59-61) | 
| 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 | 
| Functional parameters | Body weight Supplementary feeding | Baseline until day 52 | 
| Quality of life | Quality of life will be evaluated by questionnaires | Baseline versus day 52 | 
| Pharmacodynamics | Pharmacodynamics measured by body sway and questionnaires (VASBond & Lader and VASBowdle) | Baseline versus day 15 and day 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic pancreatitis, abdominal pain, visceral pain, chronic pain