The safety, tolerability, and analgesic efficacy of Δ9-THC (Namisol®) in chronic pancreatitis patients suffering from persistent abdominal pai

Phase 2

Completed

• Conditions: viscerale pijn; chronic pancreas inflammation; Chronic pancreatitis; 10015674

• Registration Number: NL-OMON35767
• Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

1. Patient is 18 years or older on the day the informed consent form will be signed.
2. Patient is male.
3. Patient has chronic pancreatitis, diagnosed using the Marseille and Cambridge Classification System (addendum II).37
4. Patient suffers from chronic abdominal pain typical for pancreatitis, meet the criteria for chronic pain according ISAP (intermittent or persistent pain on a daily basis in at least 3 months)38, and consider their pain must as severe enough for medical treatment (average NRS >= 3).
5. Patient in de opioid subgroup takes stable doses of opioids, e.g. morphine or tramadol, for the past 2 months on the day of screening. Stable dose intake is defined as a daily equivalent sum of opioid intake according medical prescription within a small deviation range as judged by the (principal) investigator.
6. Patient in the non-opioid group does not take any opioids for the past 2 months on the day of screening.
7. Patient is willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other trial procedures.
8. Patient is able to speak, read and understand the local language of the investigational site, is familiar with the procedures of the study, and agrees to participate in the study program by giving oral and written informed consent prior to screening evaluations.

Exclusion Criteria

1. Patient used any cannabinoid (by smoking cannabis or oral intake) for at least one year on the day of screening.
2. Patient is insulin dependent for more than 5 years on the day of screening.
3. Patient does not feel a pinprick test in the lower extremities, due to affected sensory input (e.g. neuropathy as a result of diabetes mellitus).
4. Patient has a body mass index (BMI) below 18 or above 31.2 kg/m2.
BMI (kg/m²) = weight (kg) / (height * height) (m2)
5. Patient suffers from serious painful conditions other than chronic pancreatitis or had any major pre-existing chronic pain syndrome.
6. Patient has a (history of) a significant medical disorder that, in the opinion of the investigator, may interfere with the study or may pose a risk for the patient.
7. Patient uses any kind of concomitant medication that, in the opinion of the investigator, may interfere with the study or may pose a risk for the patient (e.g. HIV antivirals).
8. Patient gets enteral feeding.
9. Patient takes amitriptyline on a daily basis.
10. Patient takes more than 20 mg benzodiazepines 6 hours prior or following intake of study medication (11 hour am) according prescription.
11. Patient demonstrates deviating electrocardiogram (ECG) parameters at screening, e.g. heart rate >100 bpm, QRS duration >120 msec, QTc interval >450 msec, PR interval >210 msec, any clinically significant rhythm abnormality.
12. Patient is previously diagnosed with moderate to severe renal impairment, e.g. creatinine values > 2x ULN and/or a significant change of their normal values.
13. Patient is previously diagnosed with moderate to severe hepatic failure or show significant clinical abnormalities in biochemistry blood sample as judged by the investigator.
14. Patient has a presence or history of major psychiatric illness as judged by investigator, e.g. major depression, schizophrenia.
15. Patient has experienced an epileptic seizure in the past.
16. Patient demonstrates clinically significant laboratory abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
17. Patient has a history of sensitivity / idiosyncrasy to THC, compounds chemically related to these compounds, or to any other related drug used in the past.
18. Patient has a known or suspected lactose intolerance.
19. Patient shows a positive alcohol breath test at screening or admission and/or is unable/unwilling to refrain from alcohol use from 48 hours before each study day until the last blood sample has been drawn.
20. Patient demonstrates a positive urine drug screen at screening visit for THC, cocaine, MDMA, and amphetamines.
21. Patient demonstrates a positive test result on hepatitis B surface antigen, hepatitis C antibody or HIV antibody test.
22. Patient is unwilling or unable to comply with the lifestyle guidelines.
23. Patient intends to conceive a child during the course of the study.
24. Patient participates in another investigational drug study within 90 days prior to the first dose and/or participates in more than 2 clinical trials in the last year.
25. Patient has a clinical significant exacerbation in illness within two weeks of participating in this study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Pain intensity:<br /><br>- VAS in rest<br /><br>- VAS on movement</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Nociceptive parameters:<br /><br>• EEG<br /><br>- Event related potetentials to noxious electrical stimuli<br /><br>- FFT spontaneous EEG<br /><br>• QST<br /><br>- Pressure pain tolerance thresholds<br /><br>- VAS to noxious electrical stimuli<br /><br>• DNIC<br /><br><br /><br>Pharmacokinetics:<br /><br>- Cmax, AUClast, AUC*, tmax, *z, and t1/2term for THC, 11-OH-THC and THC-COOH<br /><br><br /><br>Pharmacodynamics:<br /><br>- VASBond,<br /><br>- VASBowdle<br /><br>- Body sway<br /><br><br /><br>Safety en tolerability:<br /><br>- Vital signs (ECG, HRV, HF, BP)<br /><br>- Safety laboratory<br /><br>- Adverse events</p><br>