JMIR Publications

ABSTRACT

Background:

Abdominal pain is the hallmark symptom of chronic pancreatitis (CP). Despite incomplete efficacy and adverse effects, opioids remain a mainstay of therapy. One off-target effect of opioids is opioid-induced hyperalgesia, partially due to activation of the voltage-gated sodium channel NaV1.7. Preclinical observations demonstrate that the combination of an opioid and the anti-seizure drug lacosamide diminishes NaV1.7 current and improves pain control.

Objective:

In this phase 1 trial, we aim to: 1. determine the safety, tolerability and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP; 2. assess the feasibility of performance of a pilot study adding lacosamide to opioids in CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in painful CP.

Methods:

Utilizing the Bayesian optimal interval design, we will conduct a dose-escalation trial of lacosamide added to opioid therapy in patients with painful CP, enrolled in cohorts of size 3. The initial dose will be 50mg po bid followed by incremental increases to a maximum dose of 400mg/day, with lacosamide administered 7 days at each dose level. Adverse events will be documented according to CTCAEv5.0.

Results:

N/A

Conclusions:

This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety with opioids in CP. It is anticipated that: 1. lacosamide will prove to be safe and well-tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in painful CP; 2. lacosamide combined with opiates will lower the opioid dose necessary for pain relief and serve to improve the safety profile of opioid use in CP. Clinical Trial: Clinicaltrials.gov (https://www.clinicaltrials.gov/): NCT05603702)