Gastric Motility DisorderPhase 4NCT01055704
Effect of Methylnaltrexone on GI Transit in Healthy Volunteers
A Phase 4 study testing Methylnaltrexone only, Codeine only and Methylnaltrexone + codeine in people with Gastric Motility Disorder, run by Mayo Clinic at 1 site in United States.
Trial summary
This is a single-center, randomized, double blind, placebo-controlled study evaluating the effects of placebo, codeine, methylnaltrexone and codeine with methylnaltrexone on gastrointestinal motility and colonic transit of solids in healthy human subjects. The hypotheses are: 1. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Gastric Motility Disorder
- What is being tested?
- Methylnaltrexone only, Codeine only and Methylnaltrexone + codeine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Feb 2010
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males and non-pregnant, non-breastfeeding females
- 18-65 years old
- No functional GI disorders on the short Bowel Disease Questionnaire (BDQ)
- A BMI greater than 22.0
Who cannot join
- Structural or metabolic diseases/conditions that affect the gastrointestinal system or functional gastrointestinal disorders. The short version of the Bowel Disease Questionnaire (BDQ) will be exclude functional GI disorders. More than three positive responses will exclude participation.
- Unable to withdraw from the following medications 48 hours prior to study entry:Any medication that alters GI transit including but not limited to laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants, SSRI and newer antidepressants; analgesic drugs including opiates, NSAID, COX 2 inhibitors (note : Tylenol is permitted); GABAergic agents and benzodiazepines. Note: Concomitant medications will be reviewed on a case by case basis by the study physicians.
- Subjects who are considered by the investigator to be alcoholics not in remission or known substance abusers. Alcohol must be avoided from seven days prior to beginning the study medication until the completion of the study.
- Subjects who have participated in another clinical study within the past 30 days.
- Clinical evidence (including physical exam and review of the medical history) of significant cardiovascular, respiratory, renal, hepatic, pulmonary, gastrointestinal, hematological, neurological, psychiatric, or other disease that interfere with the objectives of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Methylnaltrexone on Gastrointestinal and Colonic Transit in Health
This is a single-center, randomized, double blind, placebo-controlled study evaluating the effects of placebo, codeine, methylnaltrexone and codeine with methylnaltrexone on gastrointestinal motility and colonic transit of solids in healthy human subjects.
The hypotheses are:
- Methylnaltrexone administered subcutaneously enhances gastrointestinal motility with acceleration of overall colonic transit, and ascending colon emptying of solids in healthy humans.
- Methylnaltrexone significantly accelerates colonic transit that is delayed by codeine
Read the detailed description
Methodology
Following the initial screening visit (visit 1), participants will be randomized to study medication, either 0.30mg/kg methylnaltrexone subcutaneously or placebo once daily and 30 mg codeine orally or placebo taken four times daily for a total of five days. Participants will be randomly assigned to study medication and allocation will be concealed. A urine pregnancy test will be performed for all females of child bearing potential within the 48 hours prior to the receipt of study medication. Note that females who are status post bilateral tubal ligation, hysterectomy or postmenopausal are exempted from this test. Study medication will be administered on study med days 1, 2 and 3 (visits 2, 3 and 4) at the Clinical Research Unit (CRU). Participants will return for scintigraphic assessment of gastric, small bowel and colonic transit of solids on study med days 4 and 5 (visits 5 and 6). The transit studies will be undertaken on over a 48 hour time period; no study medication is given on the final day of transit (visit 7).
Investigational product, dosage, mode of administration, duration of treatment
0.30 mg/kg methylnaltrexone or placebo subcutaneously once daily and 30 mg codeine or placebo orally four times daily for five consecutive days.
Treatment groups
- placebo + placebo (8 participants)
- placebo + codeine 120mg (8 participants)
- methylnaltrexone 0.30 mg/kg + placebo (16 participants)
- methylnaltrexone 0.30 mg/kg + codeine 120 mg (16 participants)
Efficacy assessments
- Scintigraphic gastrointestinal and colonic transit
- Assessment of bowel pattern frequency and consistency made by the patient using the bowel pattern diary
Safety assessments
No safety assessments (routine laboratory analysis, ECG etc) will be performed as both methylnaltrexone and codeine are FDA approved medications
Statistical analysis
The overall effects of the methylnaltrexone treatment on the primary and secondary response measures will be assessed using an analysis of covariance (ANCOVA) with suitable transformation for skewness in the distributions of measured responses if necessary (e.g., ANCOVA on ranks or an arcsine square root transformation for the proportion of marker in the colon at 6 hours). The covariates considered for inclusion in the analyses will be age, gender and body mass index. An a priori anticipated contrast (overall drug vs. placebo) will be examined (α = 0.05). The specific comparisons of methylnaltrexone vs placebo and codeine vs codeine plus methylnaltrexone are of significant interest, and since they are related to specific hypotheses, no change in α from 0.05 is planned.
- Conditions
- Gastric Motility Disorder
- Being tested
- Methylnaltrexone only, Codeine only, Methylnaltrexone + codeine, Placebo + placebo
- Keywords
- Methylnaltrexone, Codeine, Gastrointestinal motility, Colonic transit
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylnaltrexone onlyDrug
Also called MNTX, Relistor
0.30 mg/kg subcutaneous injection daily
Codeine onlyDrug
30 mg taken orally four times daily for 5 days
Methylnaltrexone + codeineDrug
Methylnaltrexone 0.30 mg/kg by subcutaneous injection once daily and codeine 30 mg taken orally four times daily for 5 days
Placebo + placeboDrug
Placebo subcutaneous injection once daily and placebo taken orally four times daily for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Methylnaltrexone | Experimental | Not described Receives: Drug: Methylnaltrexone only |
| Codeine | Experimental | Not described Receives: Drug: Codeine only |
| Methylnaltrexone + codeine | Experimental | Not described Receives: Drug: Methylnaltrexone + codeine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo + placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Colonic Geometric Center at 24 Hours
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
Measured: 24 hours
Secondary outcomes (7)
T1/2 of Ascending Colon Emptying
Measured: 24 hours
T1/2 of Gastric Emptying of Solid
Measured: 4 hours
Colonic Geometric Center at 4 Hours
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
Measured: 4 hours
Colonic Geometric Center at 48 Hours
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
Measured: 48 hours
Colonic Filling at 6 Hours
Percent of solids reaching the colon at 6 hours
Measured: 6 hours
Stool Frequency
Stool frequency was self reported in a daily bowel pattern diary for 13 days.
Measured: daily
Stool Consistency as Reported From the Bristol Stool Scale
Bristol Stool Scale a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation, with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.
Measured: Daily
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2010 (estimated)
- Study startNov 2009
- Primary completionFeb 2010
- Study completionFeb 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastric Motility DisorderStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Investigators
- Michael Camilleri, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01055704
- Sponsor's protocol ID
- 09-002996
- Status last verified
- Jun 2012
- First submitted
- 22 Jan 2010
- Last updated
- 25 Jun 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wong BS, Rao AS, Camilleri M, Manabe N, McKinzie S, Busciglio I, Burton DD, Ryks M, Zinsmeister AR. The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health. Aliment Pharmacol Ther. 2010 Oct;32(7):884-93. doi: 10.1111/j.1365-2036.2010.04422.x.
PubMed 20839388
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Methylnaltrexone on Gastrointestinal and Colonic Transit in Health
- ClinicalTrials.gov ID
- NCT01055704
- Acronym / sponsor ID
- 09-002996
- Conditions
- Gastric Motility Disorder
- Keywords
- Methylnaltrexone, Codeine, Gastrointestinal motility, Colonic transit
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Study start
- Nov 2009
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 26 Jan 2010 (estimated)
- Results
- Posted 8 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-center, randomized, double blind, placebo-controlled study evaluating the effects of placebo, codeine, methylnaltrexone and codeine with methylnaltrexone on gastrointestinal motility and colonic transit of solids in healthy human subjects.
The hypotheses are:
- Methylnaltrexone administered subcutaneously enhances gastrointestinal motility with acceleration of overall colonic transit, and ascending colon emptying of solids in healthy humans.
- Methylnaltrexone significantly accelerates colonic transit that is delayed by codeine
Detailed description
Methodology
Following the initial screening visit (visit 1), participants will be randomized to study medication, either 0.30mg/kg methylnaltrexone subcutaneously or placebo once daily and 30 mg codeine orally or placebo taken four times daily for a total of five days. Participants will be randomly assigned to study medication and allocation will be concealed. A urine pregnancy test will be performed for all females of child bearing potential within the 48 hours prior to the receipt of study medication. Note that females who are status post bilateral tubal ligation, hysterectomy or postmenopausal are exempted from this test. Study medication will be administered on study med days 1, 2 and 3 (visits 2, 3 and 4) at the Clinical Research Unit (CRU). Participants will return for scintigraphic assessment of gastric, small bowel and colonic transit of solids on study med days 4 and 5 (visits 5 and 6). The transit studies will be undertaken on over a 48 hour time period; no study medication is given on the final day of transit (visit 7).
Investigational product, dosage, mode of administration, duration of treatment
0.30 mg/kg methylnaltrexone or placebo subcutaneously once daily and 30 mg codeine or placebo orally four times daily for five consecutive days.
Treatment groups
- placebo + placebo (8 participants)
- placebo + codeine 120mg (8 participants)
- methylnaltrexone 0.30 mg/kg + placebo (16 participants)
- methylnaltrexone 0.30 mg/kg + codeine 120 mg (16 participants)
Efficacy assessments
- Scintigraphic gastrointestinal and colonic transit
- Assessment of bowel pattern frequency and consistency made by the patient using the bowel pattern diary
Safety assessments
No safety assessments (routine laboratory analysis, ECG etc) will be performed as both methylnaltrexone and codeine are FDA approved medications
Statistical analysis
The overall effects of the methylnaltrexone treatment on the primary and secondary response measures will be assessed using an analysis of covariance (ANCOVA) with suitable transformation for skewness in the distributions of measured responses if necessary (e.g., ANCOVA on ranks or an arcsine square root transformation for the proportion of marker in the colon at 6 hours). The covariates considered for inclusion in the analyses will be age, gender and body mass index. An a priori anticipated contrast (overall drug vs. placebo) will be examined (α = 0.05). The specific comparisons of methylnaltrexone vs placebo and codeine vs codeine plus methylnaltrexone are of significant interest, and since they are related to specific hypotheses, no change in α from 0.05 is planned.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Methylnaltrexone | Experimental | Drug: Methylnaltrexone only |
| Codeine | Experimental | Drug: Codeine only |
| Methylnaltrexone + codeine | Experimental | Drug: Methylnaltrexone + codeine |
| Placebo | Placebo comparator | Drug: Placebo + placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and non-pregnant, non-breastfeeding females
- 18-65 years old
- No functional GI disorders on the short Bowel Disease Questionnaire (BDQ)
- A BMI greater than 22.0
Key exclusion criteria (5 listed)
- Structural or metabolic diseases/conditions that affect the gastrointestinal system or functional gastrointestinal disorders. The short version of the Bowel Disease Questionnaire (BDQ) will be exclude functional GI disorders. More than three positive responses will exclude participation.
- Unable to withdraw from the following medications 48 hours prior to study entry:Any medication that alters GI transit including but not limited to laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants, SSRI and newer antidepressants; analgesic drugs including opiates, NSAID, COX 2 inhibitors (note : Tylenol is permitted); GABAergic agents and benzodiazepines. Note: Concomitant medications will be reviewed on a case by case basis by the study physicians.
- Subjects who are considered by the investigator to be alcoholics not in remission or known substance abusers. Alcohol must be avoided from seven days prior to beginning the study medication until the completion of the study.
- Subjects who have participated in another clinical study within the past 30 days.
- Clinical evidence (including physical exam and review of the medical history) of significant cardiovascular, respiratory, renal, hepatic, pulmonary, gastrointestinal, hematological, neurological, psychiatric, or other disease that interfere with the objectives of the study.
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 |
|---|---|---|
| Methylnaltrexone onlyAlso: MNTX, Relistor0.30 mg/kg subcutaneous injection daily | Drug | Methylnaltrexone |
| Codeine only30 mg taken orally four times daily for 5 days | Drug | Codeine |
| Methylnaltrexone + codeineMethylnaltrexone 0.30 mg/kg by subcutaneous injection once daily and codeine 30 mg taken orally four times daily for 5 days | Drug | Methylnaltrexone + codeine |
| Placebo + placeboPlacebo subcutaneous injection once daily and placebo taken orally four times daily for 5 days | Drug | Placebo |
Primary outcome
Colonic Geometric Center at 24 Hours
Time frame: 24 hours
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
7 secondary outcomes
T1/2 of Ascending Colon Emptying
Time frame: 24 hours
T1/2 of Gastric Emptying of Solid
Time frame: 4 hours
Colonic Geometric Center at 4 Hours
Time frame: 4 hours
Colonic Geometric Center at 48 Hours
Time frame: 48 hours
Colonic Filling at 6 Hours
Time frame: 6 hours
Stool Frequency
Time frame: daily
Stool Consistency as Reported From the Bristol Stool Scale
Time frame: Daily
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20839388Wong BS, Rao AS, Camilleri M, Manabe N, McKinzie S, Busciglio I, Burton DD, Ryks M, Zinsmeister AR. The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health. Aliment Pharmacol Ther. 2010 Oct;32(7):884-93. doi: 10.1111/j.1365-2036.2010.04422.x.
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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 Methylnaltrexone only, Codeine only and Methylnaltrexone + codeine in people with Gastric Motility Disorder, 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 4 inclusion and 5 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 25 Jun 2012. 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 8 Aug 2011). 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 Geometric Center at 24 Hours (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01055704, which also lists 1 linked publication.
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 25 Jun 2012.