Trial Outcomes & Findings for Pregabalin and Colonic Function (NCT NCT01094808)

NCT ID: NCT01094808

Last Updated: 2012-03-07

Results Overview

The sensory threshold for first perception of pain was measured by stepwise inflation of the balloon in increments of 4 mm Hg at 60 second intervals. The balloon was placed in the mid-descending or junction of the sigmoid and descending colon. During this assessment participants were asked to report when they had the first perception of pain. The investigator recorded the threshold pressure at which the participants reported this sensation.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 62 participants
• Primary outcome timeframe: approximately 60 minutes after drug administration
• Results posted on: 2012-03-07

Participant Flow

The study was conducted between April 2010 and January 2011 at the Mayo Clinic, Rochester, Minnesota.

Participant milestones

Measure	Pregabalin 75 mg Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo Subjects randomized to this arm received a single dose of placebo medication orally
Overall Study STARTED	21	20	21
Overall Study COMPLETED	20	19	21
Overall Study NOT COMPLETED	1	1	0

Reasons for withdrawal

Measure	Pregabalin 75 mg Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo Subjects randomized to this arm received a single dose of placebo medication orally
Overall Study Withdrawal by Subject	1	1	0

Baseline Characteristics

Pregabalin and Colonic Function

Baseline characteristics by cohort

Measure	Pregabalin 75 mg n=21 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally	Total n=62 Participants Total of all reporting groups
Age Continuous	32.2 years STANDARD_DEVIATION 11.9 • n=5 Participants	32.4 years STANDARD_DEVIATION 9.1 • n=7 Participants	31.6 years STANDARD_DEVIATION 11.8 • n=5 Participants	32 years STANDARD_DEVIATION 11 • n=4 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	46 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Region of Enrollment United States	21 participants n=5 Participants	20 participants n=7 Participants	21 participants n=5 Participants	62 participants n=4 Participants
Body Mass Index (BMI)	25.8 kg/m^2 STANDARD_DEVIATION 3.7 • n=5 Participants	26.7 kg/m^2 STANDARD_DEVIATION 6.3 • n=7 Participants	26.4 kg/m^2 STANDARD_DEVIATION 4.4 • n=5 Participants	26.3 kg/m^2 STANDARD_DEVIATION 0.6 • n=4 Participants

PRIMARY outcome

Timeframe: approximately 60 minutes after drug administration

The sensory threshold for first perception of pain was measured by stepwise inflation of the balloon in increments of 4 mm Hg at 60 second intervals. The balloon was placed in the mid-descending or junction of the sigmoid and descending colon. During this assessment participants were asked to report when they had the first perception of pain. The investigator recorded the threshold pressure at which the participants reported this sensation.

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Sensory Threshold for Pain	45.8 mm Hg Standard Deviation 14.9	46.7 mm Hg Standard Deviation 13.9	45.0 mm Hg Standard Deviation 14.0

PRIMARY outcome

Timeframe: Approximately 60 minutes after drug administration

The 30 mm Hg distension refers to inflation of the balloon placed in placed in the mid-descending or junction of the sigmoid and descending colon. Pain and gas were individually measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes. For the pain VAS, 0 means no pain and 100 mm means extreme pain. For the gas VAS, 0 means no gas sensation and 100 mm means extreme gas sensation. The investigator measures the mark made by the participant in mm and records this for the value of either pain or gas.

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Sensation Ratings for Pain and Gas at 30 mm Hg Distension Above Baseline Operating Pressure Sensation ratings for pain at 30 mm Hg	47.4 mm Standard Deviation 28.3	36.1 mm Standard Deviation 28.4	46.0 mm Standard Deviation 28.7
Sensation Ratings for Pain and Gas at 30 mm Hg Distension Above Baseline Operating Pressure Sensation ratings for gas at 30 mm Hg	53.4 mm Standard Deviation 27.9	33.2 mm Standard Deviation 19.6	46.6 mm Standard Deviation 22.3

PRIMARY outcome

Timeframe: Approximately 60 minutes after drug administration

Colonic compliance is a measure of the "stiffness" of the colon, that is, what pressure was needed to reach half the maximum value of the colon. After the barostat balloon catheter was inserted in the mid-descending or junction of the sigmoid and descending colon, the balloon was inflated. After an initial conditioning distension to 20 mm Hg, colonic compliance was measured by step-wise inflation with increments of 4 mm Hg. Colonic compliance was analyzed by a validated linear interpolation method. The pressure at half maximum volume serves as a summary of colonic compliance.

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Colonic Compliance	17.6 mm Hg Standard Deviation 5.1	19.1 mm Hg Standard Deviation 4.6	17.4 mm Hg Standard Deviation 4.8

PRIMARY outcome

Timeframe: The first 30 minutes postprandially, and preprandial (30 minutes)

The symmetric percent reduction in baseline colonic barostat balloon volume during the first 30 minutes postprandially (PP) corrected for the preprandial (30 min) tone, (symmetric percent change= 100*log_e[fasting/PP]). A positive symmetric percent change reflects a decrease in barostat balloon volume indicating a reduction in colonic tone. (The balloon was placed in the mid-descending or junction of the sigmoid and descending colon.)

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Postprandial Colonic Tone [Reported] as the Symmetric Percent [Change]in Baseline Colonic Barostat Balloon Volume	21.9 Symmetric percentage change Standard Deviation 12.4	35.3 Symmetric percentage change Standard Deviation 25.2	27.8 Symmetric percentage change Standard Deviation 21.8

PRIMARY outcome

Timeframe: 30 minutes after the meal

The first 30 minute postprandial motility index (MI), MI = log_e [(number of contractions * sum of amplitudes)+1]

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Postprandial Motility Index Over 30 Minutes Motility index proximal colon at 30 minutes	11.264 log mm Hg Standard Deviation 1.609	11.764 log mm Hg Standard Deviation 1.357	11.465 log mm Hg Standard Deviation 1.339
Postprandial Motility Index Over 30 Minutes Motility index distal colon at 30 minutes	8.806 log mm Hg Standard Deviation 3.095	9.783 log mm Hg Standard Deviation 2.849	9.879 log mm Hg Standard Deviation 2.235

SECONDARY outcome

Timeframe: Approximately 60 minutes after drug administration

The sensory threshold for first perception of gas was measured by stepwise inflation of the balloon in increments of 4 mm Hg at 60 second intervals. (The balloon was placed in the mid-descending or junction of the sigmoid and descending colon.) During this assessment participants were asked to report when they had the first perception of gas. The investigator recorded the threshold pressure at which the participants reported this sensation.

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Sensory Threshold for Gas	27.6 mm Hg Standard Deviation 18.3	34.3 mm Hg Standard Deviation 11.1	34.5 mm Hg Standard Deviation 16.8

SECONDARY outcome

Timeframe: Approximately 60 minutes after drug administration

The mm Hg distensions refer to the barostat balloon, which was placed in the mid-descending or junction of the sigmoid and descending colon. Pain sensation was measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes. For the pain VAS, 0 means no pain and 100 mm means extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain.

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Sensation Ratings for Pain at 16, 24, and 36 mm Hg Distension Sensation ratings of pain at 16 mm distension	28.70 mm Standard Deviation 24.27	29.00 mm Standard Deviation 28.47	34.29 mm Standard Deviation 28.24
Sensation Ratings for Pain at 16, 24, and 36 mm Hg Distension Sensation ratings of pain at 24 mm distension	43.00 mm Standard Deviation 30.66	36.84 mm Standard Deviation 28.55	39.48 mm Standard Deviation 29.78
Sensation Ratings for Pain at 16, 24, and 36 mm Hg Distension Sensation ratings of pain at 36 mm distension	44.30 mm Standard Deviation 23.96	43.37 mm Standard Deviation 26.94	47.62 mm Standard Deviation 30.45

SECONDARY outcome

Timeframe: Approximately 60 minutes after drug administration

The mm Hg distensions refer to the barostat balloon, which was placed in the mid-descending or junction of the sigmoid and descending colon. Gas sensation was measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes. For the gas VAS, 0 means no gas sensation and 100 mm means extreme gas sensation. The investigator measures the mark made by the participant in mm and records this for the value of either pain or gas.

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Sensation Ratings for Gas at 16, 24, and 36 mm Hg Distension Sensation Ratings for Gas at 16 mm Hg distention	37.40 mm Standard Deviation 25.10	30.00 mm Standard Deviation 25.25	37.14 mm Standard Deviation 22.62
Sensation Ratings for Gas at 16, 24, and 36 mm Hg Distension Sensation Ratings for Gas at 24 mm Hg distention	44.05 mm Standard Deviation 26.51	32.00 mm Standard Deviation 21.83	42.76 mm Standard Deviation 23.87
Sensation Ratings for Gas at 16, 24, and 36 mm Hg Distension Sensation Ratings for Gas at 36 mm Hg distention	49.65 mm Standard Deviation 25.06	36.58 mm Standard Deviation 22.42	46.24 mm Standard Deviation 22.36

SECONDARY outcome

Timeframe: Approximately 60 minutes after drug administration

The mm Hg distensions refer to the barostat balloon, which was placed in the mid-descending or junction of the sigmoid and descending colon. Gas sensation was measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes. For the gas VAS, 0 means no gas sensation and 100 mm means extreme gas sensation. The investigator measures the mark made by the participant in mm and records this for the value of gas. The values across the 4 distension pressures were averaged for this outcome measure.

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Gas Sensation Rating Averaged Across 4 Distension Pressures (16, 24, 30, and 36 mg Hg)	43.379 mm Standard Deviation 23.413	33.391 mm Standard Deviation 22.106	41.789 mm Standard Deviation 22.278

SECONDARY outcome

Timeframe: Approximately 60 minutes after drug administration

The mm Hg distensions refer to the barostat balloon, which was placed in the mid-descending or junction of the sigmoid and descending colon. Pain sensation was measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes. For the pain VAS, 0 means no pain and 100 mm means extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain. The values across the 4 distension pressures were averaged for this outcome measure.

Outcome measures

Measure	Pregabalin 75 mg n=20 Participants Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 Participants Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 Participants Subjects randomized to this arm received a single dose of placebo medication orally
Pain Sensation Rating Averaged Across 4 Distension Pressures (16, 24, 30, and 36 mg Hg)	44.364 mm Standard Deviation 23.478	35.301 mm Standard Deviation 22.295	43.286 mm Standard Deviation 23.678

Adverse Events

Pregabalin 75 mg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Pregabalin 200 mg

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pregabalin 75 mg n=20 participants at risk Subjects randomized to this arm received a single dose of pregabalin 75 mg orally	Pregabalin 200 mg n=19 participants at risk Subjects randomized to this arm received a single dose of pregabalin 200 mg orally	Placebo n=21 participants at risk Subjects randomized to this arm received a single dose of placebo medication orally
Cardiac disorders Tachycardia	45.0% 9/20 • Number of events 9 • 5 hours after tube placement	36.8% 7/19 • Number of events 7 • 5 hours after tube placement	38.1% 8/21 • Number of events 8 • 5 hours after tube placement
Nervous system disorders Drowsiness	20.0% 4/20 • Number of events 4 • 5 hours after tube placement	36.8% 7/19 • Number of events 7 • 5 hours after tube placement	4.8% 1/21 • Number of events 1 • 5 hours after tube placement
Nervous system disorders Dizziness	5.0% 1/20 • Number of events 1 • 5 hours after tube placement	36.8% 7/19 • Number of events 7 • 5 hours after tube placement	0.00% 0/21 • 5 hours after tube placement

Additional Information

Dr. Michael Camilleri

Mayo Clinic

Phone: 507-266-2305

Email: camilleri.michael@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place