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.

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.

Predictors for persistent neuropathic pain--a Delphi survey.

BACKGROUND: Chronic neuropathic pain has a major effect on quality of life. In order to prevent neuropathic pain from becoming chronic and improve neuropathic pain care, it is important to identify predictors associated with the persistence of neuropathic pain. OBJECTIVE: To identify potential predictors associated with the persistence of neuropathic pain. STUDY DESIGN: A 2-round Delphi study. SETTING: University Medical Center and Pain Management Research Center. METHODS: A 2-round Delphi study was conducted among 17 experts in the field of neuropathic pain. Selection of the panel was based on the citation index ranking for neuropathic pain-related research and/or membership in the neuropathic pain special interest group of the International Association for the Study of Pain (IASP), complemented with experts with demonstrated field knowledge.Potential predictors were categorized according to the International Classification of Functioning, Disability and Health model. Participants were asked to identify important predictors, suggest new predictors, and grade the importance on a 0-10 scale. For the second round, predictors were considered important if the median score was ≥ 7 and the interquartile range (IQR) ≤ 3. RESULTS: In the first round, 20 predictors were selected and 58 were added by the experts (patient characteristics [15], environmental factors [25], functions & structure [4], participation & health related quality of life [14]). In the second round, 12 predictors were considered important (patient characteristics [4; e.g., depression, pain catastrophizing], environmental factors [surgery as treatment for neuropathic pain], functions & structure [6; e.g., allodynia, duration of the complaints], participation & trait anxiety/depression as a part of health related quality of life). Presence of depression and pain catastrophizing were considered the most important predictors for chronic neuropathic pain (median ≥ 8; IQR ≤ 2). LIMITATIONS: The study design did not include plenary discussion among the experts. The meaning of the individual topics used in this study could have been subject to interpretation bias. CONCLUSIONS: Overall, psychological factors and factors related to sensory disturbances were considered important predictors for persistence of neuropathic pain. Activity related factors and previously received paramedical and alternative treatment were considered to be less important. The list of possible predictors obtained by this study may serve as a basis for development of a clinical prediction rule for chronic neuropathic pain.