Chronic abdominal pain is the hallmark symptom of chronic pancreatitis, with many patients seeking medical attention for pain control. While several management options are potentially available to gastroenterologists, outcomes are often disappointing, and opioids remain a mainstay of therapy. 

This is an NIH-funded phase 1 trial, “Safety, Tolerability and dose-limiting Toxicity of lacosamide in patients with Painful chronic Pancreatitis (STTEPP)”. Opioid-induced hyperalgesia (OIH) may occur with opioid therapy, a phenomenon resulting in dose escalation. Lacosamide, an antiseizure drug, may inhibit the effects of OIH. This may result in improved pain control with a decrease in opioid use. In trials with neuropathic pain, lacosamide reduced pain scores and was well tolerated. There are no data, however, evaluating the use of lacosamide in patients with chronic pancreatitis.

What is lacosamide?

Lacosamide is used to treat partial-onset epileptic seizures. It is also used with other medicines to treat primary generalized tonic-clonic seizures. It acts on the central nervous system to reduce the number and severity of seizures. As with other anti-epileptic drugs, lacosamide may have a variety of off-label uses, including pain management.

What is drug repurposing?

Drug repurposing explores new uses for drugs that have already been approved for other diseases. The process uses drugs that have already gone through rigorous testing – cutting down on cost and development time.

What is the goal of the clinical trial?

Dr. Fogel and his colleagues at IU hope that repurposing lacosamide in combination with opioid therapy will improve the quality of life of those suffering from chronic pancreatitis while decreasing opioid use.

The goals of the clinical trial are as follows:

1. The primary goal of the clinical trial is to evaluate the safety, tolerability and dose-limiting toxicity of adding lacosamide to opioid therapy in subjects with painful chronic pancreatitis.
2. A second primary goal is to assess the feasibility of performance of a pilot study adding lacosamide to opioid therapy in these subjects. 
3. A secondary, exploratory aim is to assess the efficacy of adding lacosamide to opioid therapy for the treatment of abdominal pain due to chronic pancreatitis.

It is anticipated that combination lacosamide plus opioid therapy will prove to be safe and well-tolerated. Furthermore, we will demonstrate that performance of this pilot trial is feasible in this patient population. Lastly, this phase 1 trial may demonstrate that the combination therapy may reduce the pain of chronic pancreatitis while limiting opioid use. The results of this pilot study will then support proceeding with a phase 2 trial assessing the efficacy of lacosamide added to opioid therapy to alleviate abdominal pain from chronic pancreatitis.

Where is the clinical trial taking place?

This is a multicenter trial taking place at five centers across the USA:

• Indiana University (lead site)
• University of Pittsburgh Medical Center
• Ohio State University
• Stanford University
• Mayo Clinic

Who can participate in the clinical trial?

Inclusion Criteria:

• Participants must be 18 years old or older at the time of informed consent;
• Suspected (YELLOW 2 or 3) or definite diagnosis of CP, as per CPDPC PROCEED study definition (Yadav et al., 2018; PMID 30325862) with ongoing symptoms of abdominal pain;
• Patients must be maintained on an opioid (except methadone or suboxone) for 4 weeks prior to enrollment for treatment of abdominal pain related to pancreatitis, with a daily morphine equivalent dose of 20-120mg;
• Ongoing symptoms of abdominal pain even with opioid use (Visual Analog Score and Brief Pain Inventory average score ≥4, at enrollment);
• ECOG Performance Status of 0-2;(Oken et al., 1982; PMID 7165009) ability to swallow and tolerate oral tablets;
• Females of childbearing potential must have a negative pregnancy test;
• The following laboratory parameters must be met: WBC count ≥ 3.0 K/mm3, absolute neutrophil count ≥ 1.5 K/mm3, hemoglobin ≥ 9 g/dL, platelets ≥ 75 K/mm3, creatinine ≤ 1.5 mg/dl, bilirubin ≤ 1.5 x ULN, AST ≤ 3 x ULN, ALT ≤ 3 x ULN; normal PR interval on baseline 12-lead EKG.

If you are unsure that your meet the inclusion criteria, please contact us for more information.

Exclusion Criteria:

• Subjects with indeterminate CP (YELLOW 1) as per PROCEED criteria;
• Treatment with any investigational agent within 30 days prior to registration, or concurrent participation in a clinical trial which involves another investigational agent;
• Rapidly escalating pain that requires parenteral (intravenous or intramuscular) opioid therapy within 30 days of enrollment Known hypersensitivity/allergic reaction to lacosamide, carbamazepine or oxcarbazepine;
• Pregnant or breastfeeding;
• Patient who has a diagnosis of epilepsy and/or is currently taking anti-epileptic drugs (other than gabapentin and pregabalin);
• Abdominal surgery or pain intervention (ERCP with sphincterotomy/stent/stone removal; celiac plexus block) within 90 days of enrollment.
• Hospitalization for pancreatitis exacerbation or pain management within 90 days of enrollment
• Patient who currently takes Suboxone or Methadone.
• Other factors which might explain the patient’s ongoing symptoms, at the discretion of the enrolling physician.
• History of autoimmune or traumatic pancreatitis, or sentinel attack of acute necrotizing pancreatitis which results in suspected disconnected duct syndrome.
• Primary pancreatic tumors- pancreatic ductal adenocarcinoma, suspected cystic neoplasm (>1cms in size or main duct involvement), neuroendocrine tumors, and other uncommon tumors.
• Pancreatic metastasis from other malignancies.
• History of solid organ transplant, HIV/AIDS.
• Known isolated pancreatic exocrine insufficiency (e.g. in the absence of any eligible inclusion criteria).
• Participants must not have medical or psychiatric illnesses or ongoing substance abuse that in the investigator’s opinion would compromise their ability to tolerate study interventions or participate in follow-up.

Get Involved

To learn more about the clinical trial and see if it is right for you, contact:

Evan L Fogel, MD, MSc
317-944-2816
efogel@iu.edu

Or 

Fletcher A White, MS, PhD
317-274-5164
fawhite@iu.edu