Clinical trial NCT00184496: Switching From Morphine to Methadone. A Clinical, Pharmacological and Pharmacogenetic Study
Official title: Switching From Morphine to Methadone. A Clinical, Pharmacological and Pharmacogenetic Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cancer
Keywords: Analgesics, Opioid/pharmacokinetics
Humans
Methadone/therapeutic use
Neoplasms/complications
pain/drug therapy
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
First posted: 2005-09-16
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cancer patients on morphine for chronic pain, with side effects or unsatisfactory pain relief, will be rotated to Methadone. We will try to find out what is the best methode to rotate, and the equivalent dosage.

Detailed description: This study is based on the clinical observation that patients who are not well controlled on morphine or oxycodone may benefit from switching to another opioid, in this case methadone. Although the mechanism for such switch is not completely understood, evidence indicates that opioids with different chemical structures have different characteristics, not least in relation to new knowledge about genetic variation in opioid receptors. Another challenge is that there is much uncertainty regarding equianalgesic dose ratios for morphine and methadone. It seems that the higher the morphine doses, the relatively lower methadone doses are needed to substitute morphine. Furthermore, there is uncertainty to which switching procedures one should use, the most common ones are "stop and go" and a three days switch. Finally, it is reported that methadone may increase the QT interval of the ECG, and thus increase the risk for the ventricular arrhythmia Torsade de pointe. The aim of this randomized, open label, multicenter study is primarily to compare the switching procedures, but it will also provide more knowledge about equianalgesic dose ratios, the effect of methadone on the QT interval, genetical factors that may characterize patients needing opioid switch as well as their response to it, and finally if pharmacokinetic factors plays a role.

Eligibility criteria: Inclusion Criteria:

* • Malignant disease.

  * On morphine and in need of opioid rotation. (A patient in need of opioid rotation is defined as having insufficient pain control with or without unacceptable side effects from opioids).
  * Able to complete the planned assessment schedules.
  * Above 18 years of age.
  * If out-patient, the patient lives with someone who can observe him/her.
  * Given informed consent according to the ethical guidelines.

Exclusion Criteria:

* Not able to read or write in Norwegian
* The patient has participated in a clinical study 4 weeks prior to inclusion

Primary outcomes:
measure: The overall aim of the present study is to validate the switching procedure from morphine to methadone for patients with advanced cancer and a short life expectancy. More specifically, we will:
timeFrame: 2 weeks
Secondary outcomes:
measure: Collect blood samples for present and future genetic analyses in order to explore inter individual variations in methadone and morphine doses based upon possible polymorphisms.
timeFrame: 2 weeks
measure: Compare the QT-intervals on electrocardiograms obtained before and after start with methadone.
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Trondheim
country: Norway
facility: St Olavs Hospital
Study officials:
affiliation: St Olavs University Hospital, Trondheim
name: Stein Kaasa, MD,PhD Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moksnes K, Dale O, Rosland JH, Paulsen O, Klepstad P, Kaasa S. How to switch from morphine or oxycodone to methadone in cancer patients? a randomised clinical phase II trial. Eur J Cancer. 2011 Nov;47(16):2463-70. doi: 10.1016/j.ejca.2011.06.047. Epub 2011 Jul 19.