Clinical Trial: Methylnaltrexone for Opioid Induced Constipation

Study Status: Terminated
Recruit Status: Terminated
Study Type: Observational

Official Title: Clinical Evaluation of the Efficacy of Methylnaltrexone in Resolving Constipation Induced by Different Opioid Subtypes, Combined With Laboratory Analysis of Immunomodulato

Brief Summary:

Methylnaltrexone for the treatment of opioid-induced constipation in the setting of palliative or hospice care, is significantly more effective than placebo (1). However, in both the randomized and the open-label phase of the multi center trial showing this favorable outcome, the drug produced rescue-free laxation in only about half of the patients (2). There may be several reasons for this result, since constipation in palliative care patients often has multiple simultaneously occurring causes.

Assuming that constipation of the non-responders is still opioid-induced, one of the possible reasons for not responding to methylnaltrexone could be that central actions of opioids contribute to constipation by reducing motility of the intestines through direct actions in the spinal dorsal horn (2). However, as methylnaltrexone is a µ-receptor antagonist and not all opioids are solely µ-receptor agonists another reason may well be that successful laxation is determined by the receptor-profile of the specific opioid the patient is using.

Opioids do not only influence bowel functioning, but also immune system functioning and angiogenesis. Methylnaltrexone possibly antagonizes these changes, therefore this study will also investigate the influence of methylnaltrexone on immunologic and angiogenic parameters.


Detailed Summary:
Sponsor: VU University Medical Center

Current Primary Outcome: Rescue-free laxation response [ Time Frame: Within 4 hours after at least 2 of the first 4 doses (the first week of treatment). ]

The proportion of subjects that has a rescue-free laxation response within 4 hours after at least 2 of the first 4 doses (the first week of treatment).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to first laxation [ Time Frame: Between dosing and day 14 ]
    Time to first laxation after initiation of treatment
  • Number of laxations [ Time Frame: Between dosing and day 14 ]
    • Number of laxations per week
    • Change in BFI score between day 0 and 14
  • Laxation within 4 hours [ Time Frame: Between dosing and day 14 ]
    Presence of laxation within four hours after initiation of treatment
  • laxation within 4 hours after each dose [ Time Frame: Between dosing and day 14 ]
    Number of doses after which laxation occured within four hours after treatment administration
  • laxation within 24 hours after each dose [ Time Frame: Between dosing and day 14 ]
    Number of doses after which laxation occured within 24 hours after treatment administration
  • laxation within 4 hours after 4 out of 7 doses [ Time Frame: Between dosing and day 14 ]
    Did laxation occur within 4 hours after at least 4 out of 7 treatment administrations?


Original Secondary Outcome: Same as current

Information By: VU University Medical Center

Dates:
Date Received: December 11, 2012
Date Started: July 2012
Date Completion: September 2017
Last Updated: March 29, 2017
Last Verified: March 2017