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BMC Palliative Care
Published in: BMC Palliative Care 1/2014

Open Access 01-12-2014 | Study protocol

Clinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone

Authors: Elisabeth CW Neefjes, Maurice JDL van der Vorst, Manon SA Boddaert, Wouter WA Zuurmond, Hans J van der Vliet, Aart Beeker, Hendrik P van den Berg, Cornelis J van Groeningen, Suzan Vrijaldenhoven, Henk MW Verheul

Published in: BMC Palliative Care | Issue 1/2014

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Abstract

Background

Opioid-induced constipation (OIC) is one of the major symptoms in palliative care with a prevalence of 30-50%. Methylnaltrexone for the treatment of OIC is significantly more effective than placebo, but only in about fifty percent of the patients regardless of dose increase. Dose increases cause increased toxicity without additional efficacy, and are therefore not recommended.
While methylnaltrexone is a μ-receptor antagonist, only a few opioids are solely μ-receptor agonists. Therefore, the response to methylnaltrexone may be determined by the receptor-profile of a specific opioid. In addition, methylnaltrexone may also affect the immune system and angiogenesis as was found in pre-clinical studies. Primary aim of this study is to determine differences in the efficacy of methylnaltrexone prescribed to resolve opioid induced constipation between three commonly used opioid subtypes: morphine sulphate, oxycodone and fentanyl. Secondary aim is to explore potential immunomodulatory and antiangiogenic effects of methylnaltrexone.

Methods

In this multi-center, prospective, parallel group trial we will evaluate the efficacy of methylnaltrexone in resolving OIC occurring as a side effect of the most common opioid subtypes: morphine, oxycodone and fentanyl. In total 195 patients with OIC despite prophylactic laxatives will receive methylnaltrexone every other day up to fourteen days. Patients will report its effect in a laxation diary. Group allocation is based on the opioid type the patient is using. At the start and end of the study period patients complete the Bowel Function Index questionnaire. A subgroup of the patients will donate blood for analysis of immunomodulatory- and anti-angiogenic effects of methylnaltrexone.

Discussion

In this study we aim to determine the efficacy of methylnaltrexone per opioid subtype to reduce constipation. We expect that the outcome of this study will improve the clinical use of methylnaltraxone.

Trial registration

This trial is registered at clinicaltrials.gov: NCT01955213 and in the Dutch trial register: NTR4272.
Appendix
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Metadata
Title
Clinical evaluation of the efficacy of methylnaltrexone in resolving constipation induced by different opioid subtypes combined with laboratory analysis of immunomodulatory and antiangiogenic effects of methylnaltrexone
Authors
Elisabeth CW Neefjes
Maurice JDL van der Vorst
Manon SA Boddaert
Wouter WA Zuurmond
Hans J van der Vliet
Aart Beeker
Hendrik P van den Berg
Cornelis J van Groeningen
Suzan Vrijaldenhoven
Henk MW Verheul
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Palliative Care / Issue 1/2014
Electronic ISSN: 1472-684X
DOI
https://doi.org/10.1186/1472-684X-13-42

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