Clinical trial NCT01094808: Pregabalin and Colonic Function
Official title: Effect of Pregabalin on Colonic Sensorimotor Function in Healthy Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Healthy
Keywords: pregabalin
motor
sensation
colon
pain
gas
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Center for Research Resources (NCRR)
First posted: 2010-03-29
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: This study is being done to evaluate the effects of pregabalin, a drug approved for anticonvulsive therapy and for neuropathic pain, on colonic and sensory functions in healthy individuals.

The specific study hypotheses were as follows: 1) pregabalin increases sensation thresholds, decreases sensation ratings, and increases compliance in response to balloon distension in the colon; 2) pregabalin reduces colonic phasic and tonic motility in response to a standardized meal; and 3) sensation ratings are lower with higher colonic compliance.

Detailed description: The treatment of patients with irritable bowel syndrome and chronic abdominal pain is advancing with several effective options for symptoms related to bowel dysfunction and bloating/distension. However, there are no approved or effective centrally or peripherally acting visceral analgesics. Pregabalin has been proposed as a treatment for visceral pain, based on the pharmacological actions, and efficacy in neuropathic pain.

This was a trial of healthy adults to compare the effects of oral pregabalin, 75 mg and 200 mg versus placebo on sensation and contraction of the colon using validated methods.

All participants presented on the study day after an overnight bowel preparation with an oral colonic lavage solution and a 12-hour fast. Flexible colonoscopy to the splenic flexure was performed without sedation by one investigator. The barostat catheter (constructed at Mayo Clinic, Rochester, MN) incorporating six manometric point sensors 5 cm apart was introduced into the colon over a guidewire, and the polyethylene balloon (10 cm long, cylindrical shape with a maximum volume of 600 ml) was placed in the mid-descending or junction of the sigmoid and descending colon. A rigid-piston barostat was used to measure intraballoon pressure and volume throughout the study. After an initial inflation to a volume of 75 ml to ensure unfolding of the balloon, the operating pressure was identified as the distension pressure at which respiratory excursions were recorded clearly from the barostat tracing, and the intraballoon pressure was set 2 mm Hg above the minimal distension pressure. A conditioning distention from 0 to 36 mm Hg in increments of 4 mm Hg every 15 seconds was performed over a period of 3 minutes.

After an equilibration period of 10 minutes, colonic compliance was assessed by the ascending methods of limit (ramp-like increases of 4 mm Hg at 30 section intervals). During the assessment of colonic compliance, participants reported their thresholds for first perception, gas and pain. After another 10 minute equilibration period, fasting colonic tone was measured at operating pressure for a period of 10 minutes.

Randomized-order phasic distentions were then applied at 16, 24, 30, and 36 mm Hg above the operating pressure to measure the sensations of gas and pain. Each distention lasted 1 minute and was followed by an equilibration period at the operating pressure for 2 minutes. A 100-mm visual analog scale (VAS) was used to assess the rating of arousal and stress experienced by each participant before performing the phasic distentions. During the distentions, participants also used the 100-mm VAS to rate the intensity of gas and pain perception at 30 seconds from the start of the distention.

Colonic compliance, fasting tone, pressure thresholds for first perception, gas, and pain, and VAS scores of gas and pain during the phasic distentions were measured before administering the study medication and 1 hour after drug administration. After the postdrug assessment of sensation with phasic distentions, a 30-min assessment of fasting colonic tone was measured in each participant; this provided a baseline to compare the effect of a standard 750-ml chocolate milkshake meal across treatment groups. Postprandial tone was measured over 60 minutes, with the main focus on the first 30 minutes. When the recording was completed, the balloon was deflated and the tube removed by gentle traction.

Eligibility criteria: Inclusion criteria:

- Healthy males or females

Exclusion criteria:

* Abdominal surgery other than appendectomy, laparoscopic cholecystectomy, cesarean section, vaginal or laparoscopic hysterectomy or tubal ligation
* A history of chronic gastrointestinal or systemic illnesses that could affect gastrointestinal motility
* Any history of hypertension
* Use of medications that may alter gastrointestinal motility or interact with the study medications
* Use of any of the study medications within the past 30 days
* Pregnancy
* Chronic renal insufficiency (serum creatinine \>1.5 mg/dL)
* Psychiatric or psychologic dysfunction.

Primary outcomes:
measure: Sensory Threshold for Pain
timeFrame: approximately 60 minutes after drug administration
measure: Sensation Ratings for Pain and Gas at 30 mm Hg Distension Above Baseline Operating Pressure
timeFrame: Approximately 60 minutes after drug administration
measure: Colonic Compliance
timeFrame: Approximately 60 minutes after drug administration
measure: Postprandial Colonic Tone [Reported] as the Symmetric Percent [Change]in Baseline Colonic Barostat Balloon Volume
timeFrame: The first 30 minutes postprandially, and preprandial (30 minutes)
measure: Postprandial Motility Index Over 30 Minutes
timeFrame: 30 minutes after the meal
Secondary outcomes:
measure: Sensory Threshold for Gas
timeFrame: Approximately 60 minutes after drug administration
measure: Sensation Ratings for Pain at 16, 24, and 36 mm Hg Distension
timeFrame: Approximately 60 minutes after drug administration
measure: Sensation Ratings for Gas at 16, 24, and 36 mm Hg Distension
timeFrame: Approximately 60 minutes after drug administration
measure: Gas Sensation Rating Averaged Across 4 Distension Pressures (16, 24, 30, and 36 mg Hg)
timeFrame: Approximately 60 minutes after drug administration
measure: Pain Sensation Rating Averaged Across 4 Distension Pressures (16, 24, 30, and 36 mg Hg)
timeFrame: Approximately 60 minutes after drug administration
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iturrino J, Camilleri M, Busciglio I, Burton D, Zinsmeister AR. Effect of the alpha2delta ligand, pregabalin, on colonic sensory and motor functions in healthy adults. Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G377-84. doi: 10.1152/ajpgi.00085.2011. Epub 2011 May 19.
citation: Iturrino J, Camilleri M, Busciglio I, Burton D, Zinsmeister AR. Sensations of gas and pain and their relationship with compliance during distension in human colon. Neurogastroenterol Motil. 2012 Jul;24(7):646-51, e275. doi: 10.1111/j.1365-2982.2012.01901.x. Epub 2012 Mar 6.