Clinical trial NCT06334198: The Effect of Naldemedine on Opioid-induced Bowel Dysfunction
Official title: The Effect of Naldemedine on Opioid-induced Bowel Dysfunction. An Investigator Initiated, Randomized, Double-blinded, Placebo-controlled, Cross-over Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Opioid-Induced Bowel Dysfunction
Constipation
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2024-03-27
Enrollment: 20
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Opioid-induced bowel dysfunction is a frequent condition during opioid therapy for chronic pain. Indeed, up to 90% of people on opioid treated patients experience constipation. Standard laxative treatment is often ineffective in opioid-induced constipation, but peripheral acting mu-receptor antagonists (PAMORAs) have the potential to block the effects of opioids in the gastrointestinal tract while preserving the central analgesic effect. In this study, we will investigated the effects of Naldemedine in preventing the development of opioid-induced bowel dysfunction and constipation during treatment with tramadol


Eligibility criteria: 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 (no history of opioid use/addiction. Opioid use more than a year ago to treat pain post-surgery is accepted. Opioid use in connection with participation in a clinical trial more than a year ago is accepted)
* Between 20 and 40 years of age.
* A STAI (Spielberger State-Trait Anxiety Inventory) 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, benzodiazepine, central stimulants and/or opioids, urine drug test will be performed prior to treatment start).

* History of major mental disorders (e.g., major anxiety, major depression or treatment with psychoactive medications etc.)
* 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\*.
* 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

Primary outcomes:
measure: Total gastrointestinal transit time
timeFrame: From day 4 to day 8
measure: Colorectal transit time
timeFrame: From day 4 to day 8
Secondary outcomes:
measure: Constipation symptoms
timeFrame: From day 1 to day 10
measure: Bowel movement frequency
timeFrame: From day 1 to day 10
measure: Stool consistency
timeFrame: From day 1 to day 10
measure: Gastrointestinal symptoms
timeFrame: Day 1 and day 10
measure: Opioid-induced constipation
timeFrame: Day 1 and day 10
measure: Diagnostic evaluation of opioid-induced constipation
timeFrame: Day 10
measure: Colonic motility patterns
timeFrame: From day 4 to day 8
measure: Opiate withdrawal symptoms
timeFrame: Day 13, 14 or 15
measure: Colon volume
timeFrame: Day 10
measure: Colonic water content
timeFrame: Day 10
measure: Defecation assessment
timeFrame: Day 1 and day 10
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
Study officials:
affiliation: Aalborg University Hospital
name: Asbjørn Mohr Drewes
role: PRINCIPAL_INVESTIGATOR
References: