Clinical trial NCT01449487: Investigation of Efficacy and Safety of PPC-5650 to Experimental Induced Sensation and Pain in the Rectosigmoid
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pain
Keywords: Experimental pain
IBS
Rectum
Lead sponsor: Aros Pharma ApS
Sponsor class: INDUSTRY
First posted: 2011-10-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Postmenopausal women or women who have undergone hysterectomy, and males between 18 and 70 years of age
* Pain intensity during pain attack should be \>5 on the GSRS questionnaire
* Hypersensitivity within the last 2 years measured with the barostat
* Patients able to co-operate and tolerate the experimental procedures (as assessed in the training visit)
* Patients on stable medication
* Only patients that do not take over the counter medication 24h before the two study sessions

Exclusion Criteria:

* Any history of, or current condition or medication that, as judged by the investigator, may affect gastrointestinal function and the interpretation of the clinical data
* Any clinically relevant abnormal values from the laboratory tests on hematology, clinical chemistry, urine analyses and/or faeces testing, as judged by the investigator.
* Chronic extraintestinal pain dominating the clinical history
* Any known biochemical or structural abnormality of the digestive tract such as gluten enteropathy, bile acid diarrhea, lymphocytic colitis and/or collagenous colitis, Chronic inflammatory bowel diseases, chronic pancreatitis
* Major intra-abdominal surgery; appendectomy and minor laparoscopic gynecological surgery acceptable.
* Any planned surgical intervention within the duration of the trial.
* Any abdominal surgery
* Participation in any other clinical trial within three months prior to the pre-screening visit.
* Alcohol or drug abuse.

Primary outcomes:
measure: Effect of PPC-5650
timeFrame: Change in pain from baseline to 120 minutes
Secondary outcomes:
measure: Safety profile of PPC-5650
timeFrame: Change from baseline to 120 minutes
measure: Effect of PPC-5650
timeFrame: Change in pain from baseline to 120 minutes
measure: Central mechanisms
timeFrame: Change from baseline to 120 minutes
measure: Objective pain
timeFrame: Change from baseline to 120 minutes
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Department of Gastroenterology
Study officials:
affiliation: Mech-Sense, Aalborg Hospital, Aalborg, Denmark
name: Asbjørn M Drewes, Professor
role: STUDY_DIRECTOR
References: