NCT05603702

STTEPP: Safety, Tolerability and Dose Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Indiana University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The investigators propose to conduct a dose-escalation trial of an FDA-approved antiepileptic drug, lacosamide, added to opioid therapy in patients with chronic abdominal pain from chronic pancreatitis (CP). This pilot trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of lacosamide used concomitantly with opioids in this patient population to reduce the condition known clinically as opioid-induced hyperalgesia (OIH).

Detailed description

One rather pronounced adverse off-target effect of opioids is an increasing sensitivity to noxious stimuli, even evolving a painful response to previously non-noxious stimuli, known clinically as opioid-induced hyperalgesia (OIH). Based on pre-clinical published data, therapeutic targeting of the sodium channel NaV1.7 may address one of the mechanisms that limits opioid efficacy for controlling pain. The investigators hypothesize that lacosamide, an FDA-approved antiepileptic drug that targets NaV1.7, used concomitantly with opioids will improve the opioid efficacy for controlling pain in patients with chronic pancreatitis (CP). However, there are no preliminary data available evaluating lacosamide in this patient population. Therefore, a phase 1 trial is necessary. The investigators will employ the Bayesian optimal interval (BOIN) design to find the Maximum Tolerated Dose (MTD). The investigators will enroll and treat patients in cohorts of size 3. The initial dose will be 50mg po bid (100mg/day), followed by incremental increases of 100mg/day in two divided doses. The maximum daily dose of lacosamide will be 400mg/day. Duration of lacosamide administration will be 7 days at each dose level. Follow-up laboratory parameters (as obtained at study entry) will be obtained on day 8 (with a 3 day window) after therapy is completed. A follow-up phone visit will occur on day 21 (with a 3-day window) to assess for adverse events and medication changes. It is anticipated that lacosamide will prove to be safe and well-tolerated. The results of this pilot study will then support proceeding with a subsequent phase 2 trial assessing the efficacy of lacosamide added to opioid therapy to alleviate abdominal pain from CP. The investigators further anticipate that lacosamide combined with opiates will substantially lower the opioid dose necessary for adequate pain relief and serve to substantially improve the safety profile of opioid use for CP.

Conditions

• Chronic Pain
• Chronic Pain Syndrome
• Chronic Pancreatitis
• Hyperalgesia
• Opioid Use Disorder
• Opioid-Related Disorders
• Opioid Dependence
• Chronic Abdominal Pain
• ERCP
• Pancreatic Surgery

Interventions

Type	Name	Description
DRUG	Lacosamide	Study Visit 1: Baseline study assessments will be made and questionnaires completed in person, on day 0. Drug treatment days will then occur on days 1-7. Study Visit 2: Following completion of the 7-day drug treatment period, participants will have a face-to-face clinic visit on day 8 (with a 3 day grace period), where similar assessments and questionnaires will again be completed. Participants will return all unused drug at this visit, for disposal and to monitor compliance. A follow-up phone visit will occur on day 21 (with a 3 day window) to assess for adverse events and medication changes

Timeline

• Start date: 2023-03-17
• Primary completion: 2026-03-31
• Completion: 2026-03-31
• First posted: 2022-11-03
• Last updated: 2026-03-05

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study