Clinical trial NCT01331213: Pregabalin on Colonic Motor and Sensory Function in Constipation Predominant Irritable Bowel Syndrome
Official title: Effect of Pregabalin on Colonic Motor and Sensory Function in Adults With Irritable Bowel Syndrome With Predominant Constipation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Irritable Bowel Syndrome
Keywords: Pregabalin
Irritable Bowel Syndrome
motor
sensation
colon
human
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Center for Research Resources (NCRR)
First posted: 2011-04-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The general aim of the current study is to describe the effect of pregabalin on colonic and sensory functions in adults with constipation predominant irritable bowel syndrome (IBS-C).

Study hypotheses:

1. Single-dose pregabalin 200mg increases sensation thresholds and decreases sensation ratings in response to balloon distension in the colon relative to pre-pregabalin treatment.
2. Single-dose pregabalin 200 mg will increase colonic compliance and decrease colonic pain and gas thresholds in patients with irritable bowel syndrome constipation predominant.
3. Single-dose pregabalin 200mg increases the colonic phasic and tonic response to a standardized meal.

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 in adults with IBS-C to compare the effects of oral pregabalin 200 mg versus placebo on colon motility, sensation, and tone.

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 20 mmHg in increments of 2 mmHg every 15 seconds was performed over a period of 75 seconds.

After an equilibration period of 10 minutes, a 100-mm visual analog scale (VAS) was used to assess the level of anxiety or stress experienced by each subject because they are potentially significant covariates in the assessment of visceral sensation scores.

Colonic compliance was assessed by the ascending methods of limit (ramp-like increases of 4 mm Hg at 60-second 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 mmHg 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:

- Male or females with Constipation Predominant IBS, age 18-65

Exclusion criteria:

* Abdominal surgery other than appendectomy, laparoscopic cholecystectomy, cesarean section, vaginal or laparoscopic hysterectomy or tubal ligation
* Uncontrolled hypertension
* Use of medications that may interact with the study medication
* Use of any of the study medications within the past 30 days
* Pregnancy
* History of chronic renal insufficiency (serum creatinine \>1.5mg/dL)
* Psychiatric or psychologic dysfunction
* Current pelvic floor dysfunction
* diagnosis of lactose intolerance

Primary outcomes:
measure: Colonic Compliance
timeFrame: baseline (1 hour before drug administration), post-treatment (1 hour 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: Sensory Threshold for Pain
timeFrame: approximately 60 minutes after drug administration
measure: Overall Sensory Ratings in Response to 16, 24, 30 and 36 mm Hg Distensions.
timeFrame: Approximately 60 minutes after drug administration
Secondary outcomes:
measure: Fasting Colonic Tone
timeFrame: Approximately 60 minutes after drug administration
measure: Colonic Motility Index
timeFrame: Approximately 1 hour after meal
measure: Post-treatment Sensory Threshold for Gas
timeFrame: Approximately 60 minutes after drug administration
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References: