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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Chronic Pain, Postsurgical Pain, Abdominal Pain

Intervention / Treatment
-----------------
* Drug: Tetrahydrocannabinol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 to the Namisol arm.<br>|

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 |
| --- | --- | --- |
| 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) | 
| Quality of life | Quality of life will be evaluated by questionnaires | Baseline versus day 52 | 

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