Pregabalin and Colonic Function

NCT01094808 | Completed Phase 4 Results DMC

• 5 other identifiers: 09-0084691RC1DK086182R01DK079866R01DK067071UL1RR024150
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

pregabalin; motor; sensation; colon; pain; gas

Outcome Measures

Primary Outcomes (5)

• Sensory Threshold for Pain

  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.

  approximately 60 minutes after drug administration

• Sensation Ratings for Pain and Gas at 30 mm Hg Distension Above Baseline Operating Pressure

  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.

  Approximately 60 minutes after drug administration

• Colonic Compliance

  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.

  Approximately 60 minutes after drug administration

• Postprandial Colonic Tone [Reported] as the Symmetric Percent [Change]in Baseline Colonic Barostat Balloon Volume

  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.)

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

• Postprandial Motility Index Over 30 Minutes

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

  30 minutes after the meal

Secondary Outcomes (5)

• Sensory Threshold for Gas

  Approximately 60 minutes after drug administration

• Sensation Ratings for Pain at 16, 24, and 36 mm Hg Distension

  Approximately 60 minutes after drug administration

• Sensation Ratings for Gas at 16, 24, and 36 mm Hg Distension

  Approximately 60 minutes after drug administration

• Gas Sensation Rating Averaged Across 4 Distension Pressures (16, 24, 30, and 36 mg Hg)

  Approximately 60 minutes after drug administration

• Pain Sensation Rating Averaged Across 4 Distension Pressures (16, 24, 30, and 36 mg Hg)

  Approximately 60 minutes after drug administration

Study Arms (3)

Pregabalin 75 mg

EXPERIMENTAL

Subjects randomized to this arm received a single dose of pregabalin 75 mg orally

Drug: Pregabalin; Other: Bowel preparation

Pregabalin 200 mg

EXPERIMENTAL

Subjects randomized to this arm received a single dose of pregabalin 200 mg orally

Drug: Pregabalin; Other: Bowel preparation

Placebo

PLACEBO COMPARATOR

Subjects randomized to this arm received a single dose of placebo medication orally

Drug: Placebo; Other: Bowel preparation

Interventions

Pregabalin DRUG

FDA approved medication (capsules) at 75 mg and 200 mg doses

Also known as: Lyrica

Pregabalin 200 mg; Pregabalin 75 mg

Placebo DRUG

Placebo capsules

Placebo

Bowel preparation OTHER

Polyethylene glycol electrolyte solution bowel preparation

Also known as: GoLYTELY

Placebo; Pregabalin 200 mg; Pregabalin 75 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Healthy males or females

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• 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.

  PMID: 21596994 RESULT

• 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.

  PMID: 22393902 DERIVED

MeSH Terms

Conditions

Pain; Mucopolysaccharidosis IV

Interventions

Pregabalin; Cathartics; Golytely

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Gastrointestinal Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Dr. Michael Camilleri
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-266-2305

Study Officials

• Michael Camilleri, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 29, 2010
• Study Start: March 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: March 7, 2012
• Results First Posted: March 6, 2012

Record last verified: 2012-03

Locations

US (1)