Irritable Bowel SyndromePhase 4NCT01331213
Pregabalin on Colonic Motor and Sensory Function in Constipation Predominant Irritable Bowel Syndrome
A Phase 4 study testing Pregabalin in people with Irritable Bowel Syndrome, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Irritable Bowel Syndrome
- What is being tested?
- Pregabalin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Feb 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or females with Constipation Predominant IBS, age 18-65
Who cannot join
- 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)
Show all 9Show fewer
- Psychiatric or psychologic dysfunction
- Current pelvic floor dysfunction
- diagnosis of lactose intolerance
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Effect of Pregabalin on Colonic Motor and Sensory Function in Adults With Irritable Bowel Syndrome With Predominant Constipation
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:
- Single-dose pregabalin 200mg increases sensation thresholds and decreases sensation ratings in response to balloon distension in the colon relative to pre-pregabalin treatment.
- Single-dose pregabalin 200 mg will increase colonic compliance and decrease colonic pain and gas thresholds in patients with irritable bowel syndrome constipation predominant.
- Single-dose pregabalin 200mg increases the colonic phasic and tonic response to a standardized meal.
Read the 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.
- Conditions
- Irritable Bowel Syndrome
- Being tested
- Pregabalin, Placebo
- Keywords
- Pregabalin, Irritable Bowel Syndrome, motor, sensation, colon, human
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregabalinDrug
Also called Lyrica
FDA approved medication (capsules) at 200mg dose.
PlaceboDrug
Placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| Pregabalin | Active comparator | Subjects randomized to this arm received a single dose of pregabalin 200mg orally. Receives: Drug: Pregabalin |
| Placebo | Placebo comparator | Subjects randomized to this arm received a single dose of placebo orally. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Colonic Compliance
Colonic compliance is a measure of the "stiffness" of the colon, that is, what pressure was needed to reach half the maximum volume 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.
Measured: baseline (1 hour before drug administration), post-treatment (1 hour 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.)
Measured: The first 30 minutes postprandially, and preprandial (30 minutes)
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.
Measured: approximately 60 minutes after drug administration
Overall Sensory Ratings in Response to 16, 24, 30 and 36 mm Hg Distensions.
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.
Measured: Approximately 60 minutes after drug administration
Secondary outcomes (3)
Fasting Colonic Tone
Colonic tone is a measurement of the volume of the colon. Colonic tone was assessed by noting the changes in the balloon volume in the presence of a constant operating pressure in the balloon (in the barostat-manometric assembly placed in the colon.)
Measured: Approximately 60 minutes after drug administration
Colonic Motility Index
The postprandial motility index (MI)=log_e[number of contractions * sum of amplitudes) + 1] A normal fasting average motility index (MI) would be about 12. An increase in MI means an increase in the phasic contractions (in contrast to tone) which is measured as a change in volume of the barostatically-controlled balloon. (Therefore, an increase in MI means that the meal is moving more quickly through the colon.)
Measured: Approximately 1 hour after meal
Post-treatment Sensory Threshold for Gas
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.
Measured: Approximately 60 minutes after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2011 (estimated)
- Study startApr 2011
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Research Resources (NCRR)
- Investigators
- Michael Camilleri, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01331213
- Sponsor's protocol ID
- 11-000485
- Other IDs
- UL1RR024150
- Status last verified
- Jan 2014
- First submitted
- 6 Apr 2011
- Last updated
- 3 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Pregabalin on Colonic Motor and Sensory Function in Adults With Irritable Bowel Syndrome With Predominant Constipation
- ClinicalTrials.gov ID
- NCT01331213
- Acronym / sponsor ID
- 11-000485
- Conditions
- Irritable Bowel Syndrome
- Keywords
- Pregabalin, Irritable Bowel Syndrome, motor, sensation, colon, human
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Center for Research Resources (NCRR)
- Study start
- Apr 2011
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 7 Apr 2011 (estimated)
- Results
- Posted 3 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Single-dose pregabalin 200mg increases sensation thresholds and decreases sensation ratings in response to balloon distension in the colon relative to pre-pregabalin treatment.
- Single-dose pregabalin 200 mg will increase colonic compliance and decrease colonic pain and gas thresholds in patients with irritable bowel syndrome constipation predominant.
- 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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregabalin | Active comparator | Drug: PregabalinSubjects randomized to this arm received a single dose of pregabalin 200mg orally. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects randomized to this arm received a single dose of placebo orally. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Male or females with Constipation Predominant IBS, age 18-65
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PregabalinAlso: LyricaFDA approved medication (capsules) at 200mg dose. | Drug | Pregabalin |
| PlaceboPlacebo capsules | Drug | Placebo |
Primary outcome
Colonic Compliance
Time frame: baseline (1 hour before drug administration), post-treatment (1 hour 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 volume 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.
Postprandial Colonic Tone [Reported as the Symmetric Percent [Change} in Baseline Colonic Barostat Balloon Volume
Time frame: 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.)
Sensory Threshold for Pain
Time frame: 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.
Overall Sensory Ratings in Response to 16, 24, 30 and 36 mm Hg Distensions.
Time frame: 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.
3 secondary outcomes
Fasting Colonic Tone
Time frame: Approximately 60 minutes after drug administration
Colonic Motility Index
Time frame: Approximately 1 hour after meal
Post-treatment Sensory Threshold for Gas
Time frame: Approximately 60 minutes after drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Camilleri, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pregabalin in people with Irritable Bowel Syndrome, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Colonic Compliance (time frame: baseline (1 hour before drug administration), post-treatment (1 hour after drug administration)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2014.