- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06385561
The Influence of Tramadol on Opioid-induced Bowel Dysfunction
April 24, 2024 updated by: Asbjørn Mohr Drewes
The Influence of Tramadol on Opioid-induced Bowel Dysfunction - An Investigator Initiated, Randomized, Double-blinded, Placebo-controlled, Cross-over Clinical Trial
Tramadol is a weak opioid and widely used to treat moderate to severe pain.
Stronger opioids are known to inhibit gastrointestinal motility and secretion, however the effects of tramadol on gastrointestinal function remains less understood.
The aim of this study was to determine to what degree tramadol causes opioid-induced bowel dysfunction by using an objective design to explore gastrointestinal transit, motility pattern, secretion, and colonic volume, in a group of healthy male volunteers.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Aalborg, Denmark, 9000
- Aalborg University Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Healthy (assessed by a study-affiliated medical doctor.)
- Signed informed consent.
- Able to read and understand Danish.
- Male (to avoid influence of menstrual cycles)
- Northern European descent (to minimize genetic variance influences on drug metabolism).
- The researcher believes that the participant understands the study details, is compliant and is expected to complete the study.
- Opioid naïve* (who have not taken prescription opioid for one week or longer and at least a year have passed since completion of a previous opioid study.)
- Between 20 and 40 years of age.
- A State Trait Anxiety Inventory (STAI) score in the range of 20-37 i.e., classified as "no or low anxiety" at inclusion.
Exclusion Criteria:
- Known hypersensitivity or allergy towards the used pharmaceutical compounds or pharmaceutical compounds similar to those used in the study.
- Less than three spontaneous bowel movements per week.
- Participation in other studies within 14 days prior to first visit.
- Expected need of medical/surgical treatment during the study.
- Any diagnosed disease, which investigator concludes will affect the trial (including all contraindicated complications: severe chronic obstructive pulmonary disease, pulmonary heart disease, severe bronchial asthma, paralytic ileus, hypercapnia, serious respiratory depression with hypoxia, moderate to severe decreased liver function, gastrointestinal obstruction or perforation, acute surgical abdominal complications such as appendicitis, Mb. Crohn's, ulcerative colitis, and toxic mega colon).
- History of substance abuse (alcohol, tetrahydrocannabinol (THC), benzodiazepine, central stimulants and/or opioids, urine drug test will be performed prior to treatment start). ¹
- History of major mental disorders (e.g., major anxiety, major depression or treatment with psychoactive medications etc.) ²
- Metal implants or pacemaker.
- Daily use of prescription only medicine
- Daily alcohol consumption
- Participation motivated by "wrongful" reasons such as poor economy, or psychosocial issues e.g., problems in the family, loneliness, sadness. People with such problems may be more likely to develop substance dependence.1
- Intake of alcohol within 48 hours before start of study period or any alcohol consumption during each study period. If consumption takes place during the study the participant will be excluded.
- Use of any analgesic medication within 48 hours before start as well as for the duration of the study. If consumption takes place during the study the participant will be excluded.
- Nicotine use
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo treatment
Placebo
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Placebo is administered orally twice daily.
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Active Comparator: Active treatment
Tramadol
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Tramadol is administered orally twice daily in a dosage of 100 mg (daily total of 200 mg)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total gastrointestinal transit time
Time Frame: From day 4 to day 8
|
Difference in hours from ingestion of a 3D Transit Capsule to expulsion of the capsule during active and placebo treatment
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From day 4 to day 8
|
Colorectal transit time
Time Frame: From day 4 to day 8
|
Difference in hours from the entering in the colon of a 3D Transit Capsule to expulsion of the capsule during active and placebo treatment
|
From day 4 to day 8
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Constipation symptoms
Time Frame: From day 1 to day 10
|
Measured on the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire (ranging from 0 (symptom absent) to 4 (very severe).
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From day 1 to day 10
|
Bowel movement frequency
Time Frame: From day 1 to day 10
|
Number of spontaneous bowel movements per day
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From day 1 to day 10
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Stool consistency
Time Frame: From day 1 to day 10
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Rated on the Bristol Stool Form Scale (ranging from type 1 (constipation) - type 7 (diarrhea))
|
From day 1 to day 10
|
Gastrointestinal symptoms
Time Frame: Day 1 and day 10
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Measured on the Gastrointestinal Symptom Rating Score (GSRS) questionnaire (ranging from 0 (no discomfort) to 6 (very severe discomfort)
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Day 1 and day 10
|
Opioid-induced constipation
Time Frame: Day 1 and day 10
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Measured by the Bowel Function Index (BFI) questionnaire (ranging from 0 (not at all) to 100 (very strong).
|
Day 1 and day 10
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Opiate withdrawal symptoms
Time Frame: Day 13, 14 or 15
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Measured by the Subjective Opiate Withdrawal Scale (ranging from 0 (not at all) to 4 /extremely)
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Day 13, 14 or 15
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Colon volume
Time Frame: Day 10
|
Volumetric quantification of the colon measured using T2-weighted MRI images
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Day 10
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Colonic water content
Time Frame: Day 10
|
Analysis of colonic water content measured using heavily T2-weighted MRI images
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Day 10
|
Colonic motility patterns
Time Frame: From day 4 to day 8
|
Number of motility patterns in the colon measured by the 3D Transit Capsule
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From day 4 to day 8
|
Diagnostic evaluation of opioid-induced constipation
Time Frame: Day 10
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Assessed using the Rome IV C6 criteria consisting of 7 items rated as either true or false. 2 or more items rated as "true" indicates functional constipation
|
Day 10
|
Gastric half emptying time
Time Frame: Day 1 and day 10
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Analysis of gastric half emptying time after ingestion of a standardized meal measured by MRI
|
Day 1 and day 10
|
Gastric contraction assessment
Time Frame: Day 1 and day 10
|
Analysis of gastric contraction amplitude after ingestion of a standardized meal measured by MRI
|
Day 1 and day 10
|
Gastric contraction assessment
Time Frame: Day 1 and day 10
|
Analysis of gastric contraction frequency after ingestion of a standardized meal measured by MRI
|
Day 1 and day 10
|
Small bowel motility assessment
Time Frame: Day 1 and day 10
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Analysis of small bowel motility after ingestion of a standardized meal measured using dynamic MRI images.
A semi-automated analysis software enables registration of small bowel motility with the calculation of regional motility maps and quantification of motility indices.
|
Day 1 and day 10
|
Small bowel water content
Time Frame: Day 1 and day 10
|
Analysis of small bowel water content measured using heavily T2-weighted MRI images
|
Day 1 and day 10
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 11, 2022
Primary Completion (Actual)
May 15, 2023
Study Completion (Actual)
May 15, 2023
Study Registration Dates
First Submitted
April 19, 2024
First Submitted That Met QC Criteria
April 24, 2024
First Posted (Actual)
April 26, 2024
Study Record Updates
Last Update Posted (Actual)
April 26, 2024
Last Update Submitted That Met QC Criteria
April 24, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Digestive System Diseases
- Substance-Related Disorders
- Signs and Symptoms, Digestive
- Narcotic-Related Disorders
- Gastrointestinal Diseases
- Constipation
- Intestinal Diseases
- Opioid-Induced Constipation
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Opioid
- Narcotics
- Tramadol
Other Study ID Numbers
- Tramadol_OIBD
- 2022-500108-23-00 (Ctis)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Data can be provided upon request
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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