Lacosamide for Chronic Pancreatitis

(STTEPP Trial)

Recruiting at 3 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests lacosamide, a drug typically used for epilepsy, to determine its effectiveness for chronic abdominal pain in individuals with chronic pancreatitis. The goal is to assess its safety and compatibility with opioids, which are commonly used to manage this pain but can worsen it over time, a condition known as opioid-induced hyperalgesia. Suitable participants have experienced ongoing abdominal pain from chronic pancreatitis and have used opioids for this pain for at least four weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that lacosamide is likely to be safe for humans?

Research has shown that the FDA has approved lacosamide for treating epilepsy, indicating a known safety record. In other studies, patients have used lacosamide without serious problems. Some reported side effects include dizziness, nausea, and headaches, but these were usually mild.

However, it is important to note that lacosamide can increase the risk of suicidal thoughts or behavior, similar to other drugs in its category. Researchers are also studying its safety when used with opioids. This trial aims to assess how well patients tolerate lacosamide when combined with opioids for chronic pancreatitis pain. As this trial is in an early stage, researchers are closely monitoring safety and will adjust doses if needed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about lacosamide for chronic pancreatitis because it offers a unique approach compared to standard treatments like enzyme supplements and pain management therapies. Unlike current options that primarily address symptoms, lacosamide works by modulating voltage-gated sodium channels, which may directly influence nerve pain associated with the condition. This novel mechanism could provide more targeted pain relief, potentially reducing the need for opioids and improving quality of life for patients with chronic pancreatitis.

What evidence suggests that lacosamide might be an effective treatment for chronic pancreatitis?

Previous studies have shown that lacosamide effectively manages nerve-related pain. Although approved for treating seizures, researchers are now investigating its use for chronic pancreatitis, which causes long-term abdominal pain. In this trial, participants will receive lacosamide in a dose escalation format to evaluate its effectiveness in reducing this pain, particularly when combined with opioids. Early signs suggest it might also alleviate opioid-induced hyperalgesia, a condition where opioids worsen pain over time. While specific data for chronic pancreatitis remains limited, the mechanism of lacosamide provides researchers with reason to believe it could be beneficial. ^{3 6 7 8 9}

Who Is on the Research Team?

Aynur Unalp-Arida, MD, PhD

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

Citations

1. researchprotocols.org researchprotocols.org/2024/1/e50513/

Safety, Tolerability, and Dose-Limiting Toxicity of ... Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical ...

2. fda.gov fda.gov/media/170701/download

Clinical Review: Motpoly XR (Lacosamide) adverse consequences, including severe trauma, depression, anxiety, and sudden death. ... This 505(b)(2) application provides no efficacy data and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38451604/

Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide ... In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP.

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05603702?draw=2&rank=1

STTEPP: Safety, Tolerability and Dose Limiting Toxicity of ... 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10958339/

Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide ... In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/216185s000lbl.pdf

Motpoly™ XR - accessdata.fda.gov MOTPOLY XR use is not recommended in patients with severe hepatic impairment. Concomitant Strong CYP3A4 and CYP2C9 Inhibitors. Dose reduction may be necessary ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/022253s046s048,022254s036s038,022255s027s030lbl.pdf

VIMPAT® (lacosamide) - accessdata.fda.gov The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/lacosamide-oral-route/description/drg-20072409

Lacosamide (oral route) - Side effects & dosage Safety and efficacy have not been established. Appropriate studies have not been performed on the relationship of age to the effects of Vimpat® ...

9. goodrx.com goodrx.com/motpoly-xr/what-is?srsltid=AfmBOopsfIa1yEaZIfIQipPtBP4U95xiZeNMzms6jZ8jHUZVZ0-BKolw

Motpoly XR (lacosamide): Uses, Side Effects, Dosage & ... What are the risks and warnings for Motpoly XR (lacosamide)? · Suicidal thoughts or behavior · Difficulty with speech, concentration, and movement.