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Chronic PainPhase 1STTEPPNCT05603702

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

A Phase 1 study testing Lacosamide in people with Chronic Pain and Chronic Pain Syndrome, run by Indiana University at 5 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lacosamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
5 sitesUnited States
Study dates
17 Mar 2023to 31 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • written informed consent and HIPAA authorization for release of personal health information;
  • ≥ 18 years old at the time of informed consent;
  • suspected (YELLOW 2 or 3) or definite diagnosis of CP, as per CPDPC PROCEED study definition 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;
  • ongoing symptoms of abdominal pain even with opioid use (VAS and BPI average score ≥4, at enrollment);
  • ECOG Performance Status of 0-2;(Oken et al., 1982)
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  • 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.

Who cannot join

  • 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);
Show all 16Show fewer
  • 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 30 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • Ohio State University

    Columbus, Ohio, 43210

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Stanford University

    Stanford, California, 94305

Other trials in United States

About this study

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).

Read the 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.

Being tested
Lacosamide
Keywords
Pancreatitis, Pancreatitis, chronic, Chronic pain, Pain, Pancreatic Diseases, Digestive System Diseases
Medical subject headings
Chronic Pain, Pancreatitis, Chronic, Hyperalgesia, Opioid-Related Disorders, Pancreatitis, Pain, Pancreatic Diseases, Digestive System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LacosamideDrug

    Also called VIMPAT

    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

Study groups in NCT05603702
Study groupRoleWhat they receive
Dose Escalation LevelExperimentalIn 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.
Receives: Drug: Lacosamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity of lacosamide in combination with opioids in CP patients will be measured by the number of grade 3 or4 toxicities reported via the CTCAE v5.0, between Day 1 through 21 day follow up.

    Dose-limiting toxicity of combination lacosamide and opioids. Patients will be examined and graded for subjective/objective evidence of developing grade 3 or 4 toxicities according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

    Measured: Day 1, 21 day follow up

  2. Tolerability of lacosamide in combination with opioids in CP patients will be evaluated by the percentage of compliance in taking lacosamide pills as directed between Day 1 and Day 7.

    Tolerability will be assessed by compliance with the intervention. Subjects will be evaluated for completing the 7-day trial. The percent of subjects taking 100%, 75%, 50% and <50% of tablets will be recorded.

    Measured: Day 1, Day 7

  3. Feasibility of performance of a pilot study adding lacosamide to opioid therapy in CP patients based on recruitment rate: measured by the proportion of eligible patients who continue from the screening visit to the enrollment visit.

    Recruitment rate (proportion of eligible patients approached who agree to participate)

    Measured: Screening visit, Enrollment visit

  4. Feasibility of performance of a pilot study adding lacosamide to opioid therapy in CP patients based on retention rate measured by the change from the screening visit to the 21 day follow-up visit.

    Dropout rate, including qualitative assessment of barriers to retention.

    Measured: Screening visit, 21 day follow-up

Secondary outcomes (4)
  1. Efficacy of adding lacosamide to opioid therapy for the treatment of abdominal pain due to CP by a 50% decrease in the VAS score from the Screening visit to the Follow-up visit day 8..

    Visual Analog Score (VAS) - a 50% decrease in score from Screening visit to Follow-up visit day 8.

    The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain."

    Measured: Screening visit, Day 8

  2. Efficacy of adding lacosamide to opioid therapy for the treatment of abdominal pain due to CP by a 50% decrease in BPI-SF average pain score from the Screening visit to the Day 8 visit.

    Brief Pain Inventory (BPI), short form average score - a 50% decrease in total score from Screening visit to Follow-up visit day 8 The BPI-SF is a validated self-reported tool that evaluates pain severity and pain interference with daily activities at the time of assessment. Possible scores for pain severity range from 0 to 10 (higher scores reflect more severe pain)

    Measured: Screening visit, Day 8

  3. Efficacy of adding lacosamide to opioid therapy for the treatment of abdominal pain due to CP by a 50% decrease in total score of the Compat-SF pain severity from the Screening visit to Follow-up visit day 8.

    Compat-SF total score - a 50% decrease in total score from Screening visit to Follow-up visit day 8 The COMPAT-SF is a validated self-reported tool specifically designed for patients with pancreatic disease. Scores for pain severity (average, worst, and least) range from 0 to 10 (higher corresponds to more pain); scores for pain triggers (including food, exercise, and thermal changes) are scored on a scale from never to always (never, rarely, sometimes, very often, always); scores for pain symptom characteristics (cramping, shooting, stabbing) are scored on a scale from 0 (none) to 10 (worst possible).

    Measured: Screening visit, Day 8

  4. Efficacy of adding lacosamide to opioid therapy for the treatment of abdominal pain due to CP by a 25% decrease in morphine milligram equivalents (MME) of opioid use from the Screening visit to Follow-up visit day 8.

    Opioid use will decrease by 25% from screening visit to Follow-up visit day 8. Patients will be asked to track all opioids taken on a drug diary from the screening visit through day 8 of study intervention. MME will be calculated to compare level of MME from screening visit to day 8.

    Measured: Screening visit, Day 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2022
  2. Study start17 Mar 2023
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
1. Patients in the first cohort are treated at dose level 1. 2. Once a cohort of three patients has been recruited at a given dose level, recruitment will temporarily be held until all three patients have been evaluated for delayed adverse events, at 21 ±3 days following completion of drug therapy. 3. To assign a dose to the next cohort of patients, conduct dose escalation/de-escalation according to BOIN design rules. 4. Repeat step 2 until the maximum sample size of 24 is reached or stop the trial if the number of patients treated at the current dose reaches 15.
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05603702
Sponsor's protocol ID
SHHBRBAPSM35
Other IDs
1R01DK132709-01
Acronym
STTEPP
Status last verified
May 2026
First submitted
18 Oct 2022
Last updated
3 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified patient data may be shared with investigators from outside institutions for ancillary studies upon request. Requests should be made to study principal investigator at efogel@iu.edu.

Publications

  • Agarwal D, Udoji MA, Trescot A. Genetic Testing for Opioid Pain Management: A Primer. Pain Ther. 2017 Jun;6(1):93-105. doi: 10.1007/s40122-017-0069-2. Epub 2017 Apr 13.

    PubMed 28409480
  • Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006 Mar;104(3):570-87. doi: 10.1097/00000542-200603000-00025.

    PubMed 16508405
  • Bannister K. Opioid-induced hyperalgesia: where are we now? Curr Opin Support Palliat Care. 2015 Jun;9(2):116-21. doi: 10.1097/SPC.0000000000000137.

    PubMed 25872113
  • Bannister K, Bee LA, Dickenson AH. Preclinical and early clinical investigations related to monoaminergic pain modulation. Neurotherapeutics. 2009 Oct;6(4):703-12. doi: 10.1016/j.nurt.2009.07.009.

    PubMed 19789074
  • Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007 Jul;48(7):1308-17. doi: 10.1111/j.1528-1167.2007.01188.x.

    PubMed 17635557
  • Cawello W. Clinical pharmacokinetic and pharmacodynamic profile of lacosamide. Clin Pharmacokinet. 2015 Sep;54(9):901-14. doi: 10.1007/s40262-015-0276-0.

    PubMed 25957198
  • Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016 Mar 18;65(1):1-49. doi: 10.15585/mmwr.rr6501e1.

    PubMed 26987082
  • Colvin LA, Fallon MT. Opioid-induced hyperalgesia: a clinical challenge. Br J Anaesth. 2010 Feb;104(2):125-7. doi: 10.1093/bja/aep392. No abstract available.

    PubMed 20086062
  • Cote GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR, Brand RE, Banks PA, Lewis MD, Disario JA, Gardner TB, Gelrud A, Amann ST, Baillie J, Money ME, O'Connell M, Whitcomb DC, Sherman S; North American Pancreatitis Study Group. Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis. Clin Gastroenterol Hepatol. 2011 Mar;9(3):266-73; quiz e27. doi: 10.1016/j.cgh.2010.10.015. Epub 2010 Oct 26.

    PubMed 21029787
  • Cote GA, Durkalski-Mauldin VL, Serrano J, Klintworth E, Williams AW, Cruz-Monserrate Z, Arain M, Buxbaum JL, Conwell DL, Fogel EL, Freeman ML, Gardner TB, van Geenen E, Groce JR, Jonnalagadda SS, Keswani RN, Menon S, Moffatt DC, Papachristou GI, Ross A, Tarnasky PR, Wang AY, Wilcox CM, Hamilton F, Yadav D; SHARP Consortium. SpHincterotomy for Acute Recurrent Pancreatitis Randomized Trial: Rationale, Methodology, and Potential Implications. Pancreas. 2019 Sep;48(8):1061-1067. doi: 10.1097/MPA.0000000000001370.

    PubMed 31404020
  • Cotton PB, Durkalski V, Romagnuolo J, Pauls Q, Fogel E, Tarnasky P, Aliperti G, Freeman M, Kozarek R, Jamidar P, Wilcox M, Serrano J, Brawman-Mintzer O, Elta G, Mauldin P, Thornhill A, Hawes R, Wood-Williams A, Orrell K, Drossman D, Robuck P. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014 May;311(20):2101-9. doi: 10.1001/jama.2014.5220.

    PubMed 24867013
  • Dean L. Lacosamide Therapy and CYP2C19 Genotype. 2018 Apr 18. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. MINI Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK493589/

    PubMed 29671994
  • Deuis JR, Dekan Z, Wingerd JS, Smith JJ, Munasinghe NR, Bhola RF, Imlach WL, Herzig V, Armstrong DA, Rosengren KJ, Bosmans F, Waxman SG, Dib-Hajj SD, Escoubas P, Minett MS, Christie MJ, King GF, Alewood PF, Lewis RJ, Wood JN, Vetter I. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 Jan 20;7:40883. doi: 10.1038/srep40883.

    PubMed 28106092
  • Due MR, Piekarz AD, Wilson N, Feldman P, Ripsch MS, Chavez S, Yin H, Khanna R, White FA. Neuroexcitatory effects of morphine-3-glucuronide are dependent on Toll-like receptor 4 signaling. J Neuroinflammation. 2012 Aug 16;9:200. doi: 10.1186/1742-2094-9-200.

    PubMed 22898544
  • Due MR, Yang XF, Allette YM, Randolph AL, Ripsch MS, Wilson SM, Dustrude ET, Khanna R, White FA. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain. PLoS One. 2014 Sep 15;9(9):e107399. doi: 10.1371/journal.pone.0107399. eCollection 2014.

    PubMed 25221944

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lacosamide in people with Chronic Pain and Chronic Pain Syndrome, run by Indiana University at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity of lacosamide in combination with opioids in CP patients will be measured by the number of grade 3 or4 toxicities reported via the CTCAE v5.0, between Day 1 through 21 day follow up. (time frame: Day 1, 21 day follow up). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05603702, which also lists 56 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.

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