Pregabalin on Colonic Motor and Sensory Function in Constipation Predominant Irritable Bowel Syndrome
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome; Constipation
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Pregabalin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): FDA approved medication (capsules) at 200mg dose.; Placebo capsules
Other intervention name(s): Lyrica
Intervention MeSH terms: Pregabalin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: Pregabalin; Irritable Bowel Syndrome; motor; sensation; colon; human