Investigation of Efficacy and Safety of PPC-5650 to Experimental Induced Sensation and Pain in the Rectosigmoid
Irritable Bowel Syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause. Patients with IBS visit the doctor more frequently, use more diagnostic tests, consume more medications, miss more workdays, and consume more overall direct costs than patients without IBS. More specific treatment of the localized symptoms of IBS is therefore needed, why the present study will investigate the effect and mechanisms of PPC-5650. PPC-5650 is a new chemical entity that can negatively modulate the activity of Acid sensing ion channels (ASICs). It is a potent low molecular weight inhibitor for this class of ion channels described to date.
It is hypothesized that safety, efficacy and mechanisms of local administration in the rectum of PPC-5650 can be evaluated by use of experimental induced sensation and pain in the rectum.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
|Official Title:||A Randomized, Double-blind, Cross-over Trial in Patients With Irritable Bowel Syndrome Investigating the Efficacy and Safety of PPC-5650 on Sensation and Pain During Standardized Stimulation of the Rectosigmoid|
- Effect of PPC-5650 [ Time Frame: Change in pain from baseline to 120 minutes ] [ Designated as safety issue: No ]Outcome measurements are achieved by use of multimodal pain responses (thermal, mechanical, electrical) in the rectosigmoid.
- Safety profile of PPC-5650 [ Time Frame: Change from baseline to 120 minutes ] [ Designated as safety issue: Yes ]By recording adverse effects as well as fysiological characters e.g. blood pressure, pulse, ECG is will be possible to assess safety profile of PPC-5650
- Effect of PPC‐5650 [ Time Frame: Change in pain from baseline to 120 minutes ] [ Designated as safety issue: No ]Outcome is achieved by measuring pain and sensory responses to experimental induced pain in the rectosigmoid by use of visual analogue scale (VAS) at VAS=1, 3, 5 and 7
- Central mechanisms [ Time Frame: Change from baseline to 120 minutes ] [ Designated as safety issue: No ]This outcome is done by use of referred pain areas to the experimental induced pain in the rectosigmoid
- Objective pain [ Time Frame: Change from baseline to 120 minutes ] [ Designated as safety issue: No ]Assessment of objective pain will be done by recording evoked brain potentials to electrical stimulation in the rectosigmoid
|Study Start Date:||January 2012|
|Study Completion Date:||May 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
|Active Comparator: PPC-5650||
Solution for administration in the rectum Single dose of 25µg/ml at a volume of 50ml
Other Name: No other name
|Placebo Comparator: Placebo||
Solution for administration in the rectum Identical tp active solution but without active drug
Other Name: No other name
Clinical pain and especially visceral pain is diffuse and widespread, and normally associated with many autonomic symptoms that may blur the characterization of disease in clinical practice. When treating clinical pain analgesic effects are difficult to evaluate due to a number of factors other than the pain intensity. These modifiers of the effect may include complaints relating to psychological, cognitive and social aspects of the illness, as well as systemic reactions. Hence, any change in these factors will invariably also interfere with pain intensity and pain quality and bias the assessment of analgesics in clinical trials.
Because of the confounders mentioned above, experimental pain models are often advantageous for characterizing analgesics. Basic mechanisms in pain perception, transduction and central processing can also be explored by means of human experimental pain models. These models, when applied to healthy volunteers or to patients, provide an important translational link between preclinical animal testing and human clinical trials. In clear contrast to clinical pain, experimental pain models allow the possibility of controlling the duration, the intensity and the nature of the pain stimulus. As pain is a multidimensional perception it is obvious that the reaction to a single stimulus of a certain modality only represents a limited part of the pain experience and therefore a variety of stimulus modalities are required to mimic the clinical situation. By use of a multi-modal pain model it is possible to induce sensation and pain in the rectum, investigating safety, effect and mechanisms of drugs.
This is an exploratory study investigating effect, mechanisms and safety of PPC-5650 to experimental induced pain in patients with IBS. The study aims to provide data to support further evaluation of PPC-5650 in the gastrointestinal area.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01449487
|Department of Gastroenterology|
|Gothenburg, Sweden, SE-413 45|
|Study Director:||Asbjørn M Drewes, Professor||Mech-Sense, Aalborg Hospital, Aalborg, Denmark|