Lacosamide for Chronic Pancreatitis

(STTEPP Trial)

Recruiting at 4 trial locations

Overseen By Evan L Fogel, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Indiana University

Must be taking: Opioids

Must not be taking: Methadone, Suboxone, Antiepileptics

Disqualifiers: Epilepsy, Pregnancy, Pancreatic tumors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 7 days per dose level

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Do I have to stop taking my current medications for the trial?

The trial requires that you continue taking your current opioid medication (except methadone or Suboxone) for at least 4 weeks before joining. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

How does the drug Lacosamide differ from other treatments for chronic pancreatitis?

Lacosamide is unique because it is primarily used as an anti-seizure medication, and its use in chronic pancreatitis is novel, as it may offer pain relief through a different mechanism than traditional enzyme replacement therapies or somatostatin analogues, which focus on enzyme regulation. ^{1 2 3 4 5}

Research Team

Aynur Unalp-Arida, MD, PhD

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Eligibility Criteria

This trial is for adults with chronic pancreatitis who still experience abdominal pain despite opioid use. They must be able to take oral tablets, not have had certain pancreatic procedures recently, and not be on methadone or suboxone. Women of childbearing age need a negative pregnancy test.

Inclusion Criteria

I can swallow and tolerate oral tablets.

Written informed consent and HIPAA authorization for release of personal health information

I am able to care for myself and perform daily activities.

Exclusion Criteria

My pancreatic tumor is one of several types, including adenocarcinoma or a suspected large cyst.

I need hospital care or strong painkillers given through a vein for my severe pain.

You have an indeterminate CP (YELLOW 1) according to PROCEED criteria.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive lacosamide in a dose-escalation manner, starting at 50mg/day and increasing to a maximum of 400mg/day over 7 days at each dose level

7 days per dose level

Daily monitoring during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with laboratory parameters obtained on day 8 and a follow-up phone visit on day 21

21 days

1 in-person visit, 1 phone visit

Extension

Potential continuation of treatment in a subsequent phase 2 trial based on pilot study results

Treatment Details

Interventions

• Lacosamide

Trial Overview The STTEPP trial is testing the safety and tolerability of Lacosamide, an antiepileptic drug, when added to opioid therapy in patients with chronic pancreatitis to see if it can reduce pain that opioids alone haven't managed.

Participant Groups

Group I: Dose Escalation Level Experimental Treatment 1 Intervention

In the first 3-patient cohort, the dose of lacosamide given is 50mg/d BID. Enrollment to the next higher dose cohort will be initiated only if none of the 3 participants exhibits a DLT in the 21 ±3 days following completion of the 7 day drug therapy. Dose escalation will proceed according to the Bayesian optimal interval (BOIN) design at incremental increase of 100mg/day in two divided doses. The maximum daily dose of lacosamide will be 400mg/day.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

In a study of 63 patients undergoing endoscopic pancreatography, the long-acting somatostatin analogue octreotide acetate significantly reduced the rise in serum amylase and lipase levels compared to a control group, indicating its efficacy in preventing enzyme elevation after the procedure.

Specifically, only 3 out of 29 treated patients experienced pathological increases in amylase, compared to 15 out of 34 in the control group, demonstrating a significant protective effect (p < 0.01) from octreotide administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of long-acting somatostatin analogue on enzyme changes after endoscopic pancreatography. Tulassay, Z., Papp, J.[2019]

Pancreatic enzyme replacement therapy is effective for managing malabsorption and chronic pain in patients with chronic pancreatitis.

For optimal treatment, high-protease enzyme preparations are recommended for pain relief, while high-lipase preparations are best for addressing steatorrhea (fat malabsorption).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzymatic therapy in patients with chronic pancreatitis. Greenberger, NJ.[2019]

Chronic feeding of camostate to rats leads to significant pancreatic growth, which is linked to increased levels of endogenous cholecystokinin due to the inhibition of trypsin in the duodenum.

The use of L-364,718, a potent cholecystokinin receptor antagonist, completely abolished the pancreatic growth induced by camostate, suggesting that cholecystokinin is crucial for this effect and may also be important for maintaining normal pancreatic growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of L-364,718, a new cholecystokinin receptor antagonist, on camostate-induced growth of the rat pancreas. Wisner, JR., McLaughlin, RE., Rich, KA., et al.[2021]

In a study of 17 patients with chronic pancreatitis, pancitrate 25,000 was effective in reducing stomach pain for 16 out of 17 patients, demonstrating its efficacy in pain management.

The treatment also helped normalize stool in 8 out of 13 patients and decreased levels of creato- and steatorea, indicating its effectiveness in addressing pancreatic secretion deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Enzyme preparations in conservative treatment of chronic pancreatitis]. Okhlobystin, AV., Bayarmaa, N.[2006]

In a study of 65 pancreas transplants over 30 months, the use of Sandostatin (a long-acting somatostatin analogue) in 23 patients significantly reduced serum, urine, and peritoneal fluid amylase levels, indicating its efficacy in managing exocrine complications like hyperamylasemia and pancreatitis.

Sandostatin therapy was associated with an 83% pancreas allograft survival rate, demonstrating its potential for graft salvage with low morbidity, although it also led to decreased levels of cyclosporine, which is important for transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective use of Sandostatin in vascularized pancreas transplantation. Stratta, RJ., Taylor, RJ., Lowell, JA., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

The effect of long-acting somatostatin analogue on enzyme changes after endoscopic pancreatography. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Enzymatic therapy in patients with chronic pancreatitis. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of L-364,718, a new cholecystokinin receptor antagonist, on camostate-induced growth of the rat pancreas. [2021]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Enzyme preparations in conservative treatment of chronic pancreatitis]. [2006]

5. United States pubmed.ncbi.nlm.nih.gov

Selective use of Sandostatin in vascularized pancreas transplantation. [2019]