Chronic Pancreatitis MedDRA version: 17.1 Level: LLT Classification code 10009093 Term: Chronic pancreatitis System Organ Class: 100000004856 MedDRA version: 17.1 Level: HLT Classification code 10033646 Term: Acute and chronic pancreatitis System Organ Class: 100000004856
Conditions
Interventions
Trade Name: S-Ketamin
Product Name: S-ketamin
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: Midazolam
Product Name: Midazolam
Pharmaceutical Form: Solution for injection/infu
Sponsors
Prof. Asbjørn Mohr Drewes
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Patients from the ages of 18 with a diagnosis of CP diagnosed using the Mayo Clinic diagnostic criteria. Both diabetic and non-diabetic patients will be allowed to enter the study. ? The participants must be able to read and understand Danish. ? The patients must suffer from chronic abdominal pain characteristic for CP, meet the criteria for chronic pain (pain = 3 days per week in at least 3 months) and must consider their pain as insufficiently treated with their usual analgesic treatment. ? Personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial. ? Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other trial procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: ? Patients with any 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. ? Undiagnosed or untreated severe hypertension. ? Unstable angina. ? Congestive heart failure. ? Any condition with elevated intracranial pressure. ? Untreated thyrotoxicosis. ? Alcohol dependence (Alcohol use in accordance with the recommendations by the Danish Health and Medicines Authority are allowed). ? Illegal drug dependencies. ? Patients with evidence or history of medical or surgical disease of importance for this study as judged by investigator. ? Patients treated with S-ketamine during the previous 4 months. ? Treatment with an investigational drug within 4 months preceding the first dose of study medication of importance for this study as judged by investigator. ? Female patients who are pregnant or lactating, or intend to become pregnant and male patients who intend to father a child during the course of the study. A pregnancy test will be conducted at baseline and after 4 weeks to ensure that female patients are not pregnant during the study medication period. The investigator will have to ensure that fertile female patients use a safe contraception method during the study and for at least 15 hours after termination of the study medication period. The following methods are considered as safe contraception methods: o The combined oral contraceptive pill o Intra uterine device o Gestagen injection o Subdermal implantation o Hormone vaginal ring o Transdermal plaster ? Patients must not suffer from painful conditions other than CP that make them unable to distinguish the pain associated with CP from chronic pain of other origin. ? Patients with known hypersensitivity to S-ketamine or any of its components.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In the clinical part the aim is to investigate the analgesic effect of S-ketamine on clinical pain resulting from CP. Hence, the primary clinical objective is to understand the effect of S-ketamine on the daily pain experienced by patients with CP as documented in a pain diary. The experimental part of the study aims at evaluating the effect of S-ketamine in controlled and standardized circumstances. Hence, using an experimental pain model the primary objective of the experimental study is to understand the analgesic and anti-hyperalgesic mechanisms of action underlying S-ketamine’s efficacy. In addition, basic pain mechanisms in CP will be explored and experimental pain models will be used to predict the clinical efficacy of s-ketamine based on patients’ sensory profile prior to treatment. Subjects will have a brain MR-I at baseline, end of study medication and at the end of the study.;Secondary Objective: Secondary objectives are to understand the effect of S-ketamine on quality of life, physical functioning including symptoms of anxiety and depression. Further secondary objectives are to understand the safety, tolerability and absorption of S-ketamine in this patient population. ;Primary end point(s): The primary efficacy parameter to be evaluated is pain relief. In the clinical part of the study the efficacy is assessed as changes in the daily experience of pain, which will be measured using a patient pain diary based on the visual analog scale (VAS). Maximum intensity and average daily VAS will be recorded on daily basis.;Timepoint(s) of evaluation of this end point: After termination of the study at day 91. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Experimental endpoints: Recording of experimental pain measures will be employed at baseline, during s-ketamine or placebo infusion, after four weeks of S-ketamine or placebo, and during the last visit at day 91 to unravel the mechanisms underlying anti-hyperalgesic and analgesic effects of S-ketamine. Furthermore, experimental baseline recordings will be compared to recordings from a group of healthy controls to evaluate general aspects of pain processing in CP. The following experimental pain measures will be employed: ? Tetanic electric stimulation (pancreatic viscerotome and control area). ? Pressure stimulation (pancreatic viscerotome and control area) and muscle (quadriceps). ? Electric stimulation (pancreatic viscerotome and control area) with recording of evoked brain potentials (EPs). ? Contact heat evoked potentials (CHEPS) (pancreatic and control area). ? Somatosensory EPs with recovery cycle estimation (median nerve). ? Nociceptive reflexes. ? Temporal summation to repetitive electric stimulations (pancreatic and control area). ? Resting state electroencephalography (EEG). ? Conditioned pain modulation (CPM). ? Offset-analgesia with recording of EPs The slope of the stimulus response curves and latency/amplitude of the EPs are considered secondary efficacy parameters. The analgesic effect is assessed as changes in the experimental endpoints. Pharmacokinetic parameters will also be secondary endpoints in this study. These parameters will be compared and associated to relevant experimental and clinical endpoints. Secondary clinical endpoints: ? The ratio of responders versus non-responders defined by a decrease in VAS > 30% after four weeks compared to baseline. ? Change in opioid consumption. ? Change in quality of life using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire EORTC-C30.15 ? Changes in pain and physical functioning composite scores of the modified brief pain inventory-sho | — |
Countries
Denmark
Contacts
Public ContactAnne Estrup Olesen
Center of Mech-Sense, Department of Gastroenterology, Aalborg University Hospital
Outcome results
None listed