Pregabalin and Colonic Function
Condition: Healthy
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Pregabalin; Placebo; Bowel preparation
Intervention type(s): Drug; Drug; Other
Intervention description(s): FDA approved medication (capsules) at 75 mg and 200 mg doses; Placebo capsules; Polyethylene glycol electrolyte solution bowel preparation
Other intervention name(s): Lyrica; GoLYTELY
Intervention MeSH terms: Pregabalin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: pregabalin; motor; sensation; colon; pain; gas