Genetic Variation in Organic Cation Transport 1 (OCT1) and Its Significance for Morphine Pharmacokinetics

Morphine Clinical Trial

Official title:

Genetic Variation in Organic Cation Transport 1 (OCT1) and Its Significance for Morphine Pharmacokinetics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03425084
• Other study ID #: AKF-391
• Status: Completed
• Phase: Phase 1
• Start date: June 1, 2018
• Est. completion date: February 7, 2020

Study information

• Verified date: January 2018
• Source: University of Southern Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of the trial is to investigate the effect of known genetic variants in organic cation transporter 1 (OCT1) on the effect of morphine after major surgery

Description:

The purpose of the experiment is to investigate the effect of known genetic variants in organic cation transporter 1 (OCT1) on the effect of morphine after major surgery. This is primarily done by investigating systemic exposure of morphine in a cohort of patients undergoing scheduled laparoscopic colon or laparoscopic rectum surgery, and as pain treatment with intravenous (iv) morphine at the end of and after surgery (primary endpoints). As a secondary endpoint, we will investigate the effect (pharmacodynamics) of morphine in the same patients by registering pain during rest and activity, side effects and the degree of sedation at appropriate time intervals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: February 7, 2020
• Est. primary completion date: February 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Planned Colectomy / Hemicolectomy, sigmoid resection, rectal resection or abdominal perianal amputation of the rectum with stoma, good general health (ASA 1 -2), Informed consent given, Age 18-90 years and BMI 18,5 - 35kg/m².

Exclusion Criteria:

• Abdominoperineal resection (APR) - ad modum Holm (abdominal perianal amputation of rectum with stoma)

• Daily use of opioids

• Indicator for the use of an epidural catheter

• Alcohol abuse

• Hypersensitivity for morphine

• A known serious disease (Terminal cancer, severe dementia, significant heart, liver, lung or renal failure or severe psychiatric disease)

• Women of childbearing age who do not use safe contraception

• Women who are breastfeeding

• Pregnant women

Related Conditions & MeSH terms

• Morphine
• Organic Cation Transporter 1

Intervention

Drug:
• Morphine
The study was designed as an open, non-controlled drug trial, with scientists and participants blinded to the patients OCT1 status. Morphine will be given as a single dosis (0,15 mg/kg) at the end of the Surgery and later as boluses of 0,04mg/kg administrated by patient-controlled analgesia, (PCA). Blood samples with drug concentrations will be used to determine a difference in morphine AUC due to the patients OCT1 status. Questionnaire answers will be used to determine the effect of morphine due to the patients OCT1 status

Locations

Country	Name	City	State
Denmark	Sydvestjysk Sygehus	Esbjerg
Denmark	Odense Universitetshospital	Odense

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern Denmark	Danish Council for Independent Research, Region of Southern Denmark, The Faculty of Health Sciences SDU

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morphine Area under the curve (AUC)	Difference in morphine AUC due to patient OCT1 status	Blood samples will be drawn at zero, five, 10, 15, 30, 45, 60 and 90 minutes after the first morphine bolus
Secondary	Morphine effect	Pain during rest and activity will be evaluated through a Numeric Rating Scale on the same patients where 0 is no pain and 10 is the the worst possible pain.	Questionnaire answers will be collected with an appropriate time interval for 24 hours after the first morphine bolus
Secondary	Morphine effect	side effects will be evaluated through a 5-point verbal questionnaire on the same patients where 0 is no side effects and 4 is unacceptable side effects.	Questionnaire answers will be collected with an appropriate time interval for 24 hours after the first morphine bolus
Secondary	Morphine effect	The degree of sedation will be evaluated through the Richmond Agitation and Sedation Scale (RASS) on the same patients	Questionnaire answers will be collected with an appropriate time interval for 24 hours after the first morphine bolus
Secondary	Morphine effect	The total dose of morphine used during the investigation.	After the trial has ended (24 hours after the first morphine bolus) data containing morphine use will be collected.
Secondary	Morphine effect	The number of administrations of morphine will be recorded	After the trial has ended (24 hours after the first morphine bolus) data containing morphine use will be collected.