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

NCT05603702 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: SHHBRBAPSM351R01DK132709-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief 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).

Conditions

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

Keywords

Pancreatitis; Pancreatitis, chronic; Chronic pain; Pain; Pancreatic Diseases; Digestive System Diseases

Outcome Measures

Primary Outcomes (4)

• 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.

  Day 1, 21 day follow up

• 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.

  Day 1, Day 7

• 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)

  Screening visit, Enrollment visit

• 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.

  Screening visit, 21 day follow-up

Secondary Outcomes (4)

• 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..

  Screening visit, Day 8

• 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.

  Screening visit, Day 8

• 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.

  Screening visit, Day 8

• 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.

  Screening visit, Day 8

Study Arms (1)

Dose Escalation Level

EXPERIMENTAL

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.

Drug: Lacosamide

Interventions

Lacosamide DRUG

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

Also known as: VIMPAT

Dose Escalation Level

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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 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.
• 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.

Sponsors & Collaborators

• Indiana University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (5)

Stanford University

Stanford, California, 94305, United States

COMPLETED

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Related Publications (56)

• 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.

  PMID: 28409480 RESULT

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

  PMID: 16508405 RESULT

• 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.

  PMID: 25872113 RESULT

• 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.

  PMID: 19789074 RESULT

• 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.

  PMID: 17635557 RESULT

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

  PMID: 25957198 RESULT

• 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.

  PMID: 26987082 RESULT

• 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.

  PMID: 20086062 RESULT

• 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.

  PMID: 21029787 RESULT

• 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.

  PMID: 31404020 RESULT

• 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.

  PMID: 24867013 RESULT

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

  PMID: 29671994 RESULT

• 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.

  PMID: 28106092 RESULT

• 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.

  PMID: 22898544 RESULT

• 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.

  PMID: 25221944 RESULT

• Elmunzer BJ, Scheiman JM, Lehman GA, Chak A, Mosler P, Higgins PD, Hayward RA, Romagnuolo J, Elta GH, Sherman S, Waljee AK, Repaka A, Atkinson MR, Cote GA, Kwon RS, McHenry L, Piraka CR, Wamsteker EJ, Watkins JL, Korsnes SJ, Schmidt SE, Turner SM, Nicholson S, Fogel EL; U.S. Cooperative for Outcomes Research in Endoscopy (USCORE). A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012 Apr 12;366(15):1414-22. doi: 10.1056/NEJMoa1111103.

  PMID: 22494121 RESULT

• Fogel EL, Lehman GA, Tarnasky P, Cote GA, Schmidt SE, Waljee AK, Higgins PDR, Watkins JL, Sherman S, Kwon RSY, Elta GH, Easler JJ, Pleskow DK, Scheiman JM, El Hajj II, Guda NM, Gromski MA, McHenry L Jr, Arol S, Korsnes S, Suarez AL, Spitzer R, Miller M, Hofbauer M, Elmunzer BJ; US Cooperative for Outcomes Research in Endoscopy (USCORE). Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol. 2020 Feb;5(2):132-141. doi: 10.1016/S2468-1253(19)30337-1. Epub 2019 Nov 25.

  PMID: 31780277 RESULT

• Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005 Mar 31;352(13):1324-34. doi: 10.1056/NEJMoa042580.

  PMID: 15800228 RESULT

• Goodman CW, Brett AS. Gabapentin and Pregabalin for Pain - Is Increased Prescribing a Cause for Concern? N Engl J Med. 2017 Aug 3;377(5):411-414. doi: 10.1056/NEJMp1704633. No abstract available.

  PMID: 28767350 RESULT

• Hall TC, Garcea G, Webb MA, Al-Leswas D, Metcalfe MS, Dennison AR. The socio-economic impact of chronic pancreatitis: a systematic review. J Eval Clin Pract. 2014 Jun;20(3):203-7. doi: 10.1111/jep.12117. Epub 2014 Mar 24.

  PMID: 24661411 RESULT

• Haugan F, Rygh LJ, Tjolsen A. Ketamine blocks enhancement of spinal long-term potentiation in chronic opioid treated rats. Acta Anaesthesiol Scand. 2008 May;52(5):681-7. doi: 10.1111/j.1399-6576.2008.01637.x.

  PMID: 18419722 RESULT

• Hearn L, Derry S, Moore RA. Lacosamide for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012 Feb 15;2012(2):CD009318. doi: 10.1002/14651858.CD009318.pub2.

  PMID: 22336864 RESULT

• Hewitt DJ. The use of NMDA-receptor antagonists in the treatment of chronic pain. Clin J Pain. 2000 Jun;16(2 Suppl):S73-9. doi: 10.1097/00002508-200006001-00013.

  PMID: 10870744 RESULT

• Ibrahim SA, Albany Z, Albany C. Significant response to lacosamide in a patient with severe chemotherapy-induced peripheral neuropathy. J Community Support Oncol. 2015 May;13(5):202-4. doi: 10.12788/jcso.0136.

  PMID: 26029937 RESULT

• Isensee J, Krahe L, Moeller K, Pereira V, Sexton JE, Sun X, Emery E, Wood JN, Hucho T. Synergistic regulation of serotonin and opioid signaling contributes to pain insensitivity in Nav1.7 knockout mice. Sci Signal. 2017 Jan 10;10(461):eaah4874. doi: 10.1126/scisignal.aah4874.

  PMID: 28074005 RESULT

• Jo S, Bean BP. Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States. Mol Pharmacol. 2017 Apr;91(4):277-286. doi: 10.1124/mol.116.106401. Epub 2017 Jan 24.

  PMID: 28119481 RESULT

• Li X, Angst MS, Clark JD. A murine model of opioid-induced hyperalgesia. Brain Res Mol Brain Res. 2001 Jan 31;86(1-2):56-62. doi: 10.1016/s0169-328x(00)00260-6.

  PMID: 11165371 RESULT

• Liang D, Shi X, Qiao Y, Angst MS, Yeomans DC, Clark JD. Chronic morphine administration enhances nociceptive sensitivity and local cytokine production after incision. Mol Pain. 2008 Feb 22;4:7. doi: 10.1186/1744-8069-4-7.

  PMID: 18294378 RESULT

• Minville V, Fourcade O, Girolami JP, Tack I. Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine. Br J Anaesth. 2010 Feb;104(2):231-8. doi: 10.1093/bja/aep363. Epub 2009 Dec 22.

  PMID: 20031953 RESULT

• Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007938. doi: 10.1002/14651858.CD007938.pub2.

  PMID: 21412914 RESULT

• Mullady DK, Yadav D, Amann ST, O'Connell MR, Barmada MM, Elta GH, Scheiman JM, Wamsteker EJ, Chey WD, Korneffel ML, Weinman BM, Slivka A, Sherman S, Hawes RH, Brand RE, Burton FR, Lewis MD, Gardner TB, Gelrud A, DiSario J, Baillie J, Banks PA, Whitcomb DC, Anderson MA; NAPS2 Consortium. Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study. Gut. 2011 Jan;60(1):77-84. doi: 10.1136/gut.2010.213835.

  PMID: 21148579 RESULT

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

  PMID: 7165009 RESULT

• Park KD, Yang XF, Dustrude ET, Wang Y, Ripsch MS, White FA, Khanna R, Kohn H. Chimeric agents derived from the functionalized amino acid, lacosamide, and the alpha-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosamide and safinamide. ACS Chem Neurosci. 2015 Feb 18;6(2):316-30. doi: 10.1021/cn5002182. Epub 2014 Dec 9.

  PMID: 25418676 RESULT

• Rao RD, Michalak JC, Sloan JA, Loprinzi CL, Soori GS, Nikcevich DA, Warner DO, Novotny P, Kutteh LA, Wong GY; North Central Cancer Treatment Group. Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3). Cancer. 2007 Nov 1;110(9):2110-8. doi: 10.1002/cncr.23008.

  PMID: 17853395 RESULT

• Rauck RL, Shaibani A, Biton V, Simpson J, Koch B. Lacosamide in painful diabetic peripheral neuropathy: a phase 2 double-blind placebo-controlled study. Clin J Pain. 2007 Feb;23(2):150-8. doi: 10.1097/01.ajp.0000210957.39621.b2.

  PMID: 17237664 RESULT

• Sarner M, Cotton PB. Classification of pancreatitis. Gut. 1984 Jul;25(7):756-9. doi: 10.1136/gut.25.7.756.

  PMID: 6735257 RESULT

• Serrano J, Andersen DK, Forsmark CE, Pandol SJ, Feng Z, Srivastava S, Rinaudo JAS; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer: From Concept to Reality. Pancreas. 2018 Nov/Dec;47(10):1208-1212. doi: 10.1097/MPA.0000000000001167.

  PMID: 30325859 RESULT

• Shaibani A, Biton V, Rauck R, Koch B, Simpson J. Long-term oral lacosamide in painful diabetic neuropathy: a two-year open-label extension trial. Eur J Pain. 2009 May;13(5):458-63. doi: 10.1016/j.ejpain.2008.05.016. Epub 2008 Jul 10.

  PMID: 18619874 RESULT

• Shaibani A, Fares S, Selam JL, Arslanian A, Simpson J, Sen D, Bongardt S. Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial. J Pain. 2009 Aug;10(8):818-28. doi: 10.1016/j.jpain.2009.01.322. Epub 2009 May 5.

  PMID: 19409861 RESULT

• Sheets PL, Heers C, Stoehr T, Cummins TR. Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. J Pharmacol Exp Ther. 2008 Jul;326(1):89-99. doi: 10.1124/jpet.107.133413. Epub 2008 Mar 31.

  PMID: 18378801 RESULT

• Stohr T, Kupferberg HJ, Stables JP, Choi D, Harris RH, Kohn H, Walton N, White HS. Lacosamide, a novel anti-convulsant drug, shows efficacy with a wide safety margin in rodent models for epilepsy. Epilepsy Res. 2007 May;74(2-3):147-54. doi: 10.1016/j.eplepsyres.2007.03.004. Epub 2007 Apr 12.

  PMID: 17433624 RESULT

• Sutton KG, Martin DJ, Pinnock RD, Lee K, Scott RH. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol. 2002 Jan;135(1):257-65. doi: 10.1038/sj.bjp.0704439.

  PMID: 11786502 RESULT

• Tirkes T, Yadav D, Conwell DL, Territo PR, Zhao X, Venkatesh SK, Kolipaka A, Li L, Pisegna JR, Pandol SJ, Park WG, Topazian M, Serrano J, Fogel EL; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Magnetic resonance imaging as a non-invasive method for the assessment of pancreatic fibrosis (MINIMAP): a comprehensive study design from the consortium for the study of chronic pancreatitis, diabetes, and pancreatic cancer. Abdom Radiol (NY). 2019 Aug;44(8):2809-2821. doi: 10.1007/s00261-019-02049-5.

  PMID: 31089778 RESULT

• Vardanyan A, Wang R, Vanderah TW, Ossipov MH, Lai J, Porreca F, King T. TRPV1 receptor in expression of opioid-induced hyperalgesia. J Pain. 2009 Mar;10(3):243-52. doi: 10.1016/j.jpain.2008.07.004. Epub 2008 Sep 6.

  PMID: 18774343 RESULT

• Venier J, Herrick R, Norris C, Liu S, Zhang L, Yuan Y Bayesian Optimal Interval (BOIN) Phase I Design (PID-862): Version 1.0.4. In. Houston, TX: The University of Texas MD Anderson Cancer Center.

  RESULT

• Vera-Portocarrero LP, Zhang ET, King T, Ossipov MH, Vanderah TW, Lai J, Porreca F. Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain. 2007 May;129(1-2):35-45. doi: 10.1016/j.pain.2006.09.033. Epub 2006 Nov 22.

  PMID: 17123731 RESULT

• Wang Y, Wilson SM, Brittain JM, Ripsch MS, Salome C, Park KD, White FA, Khanna R, Kohn H. Merging Structural Motifs of Functionalized Amino Acids and alpha-Aminoamides Results in Novel Anticonvulsant Compounds with Significant Effects on Slow and Fast Inactivation of Voltage-gated Sodium Channels and in the Treatment of Neuropathic Pain. ACS Chem Neurosci. 2011 Jun 15;2(6):317-322. doi: 10.1021/cn200024z.

  PMID: 21765969 RESULT

• Wehler M, Reulbach U, Nichterlein R, Lange K, Fischer B, Farnbacher M, Hahn EG, Schneider T. Health-related quality of life in chronic pancreatitis: a psychometric assessment. Scand J Gastroenterol. 2003 Oct;38(10):1083-9. doi: 10.1080/00365520310005956.

  PMID: 14621285 RESULT

• Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD005451. doi: 10.1002/14651858.CD005451.pub2.

  PMID: 21249671 RESULT

• Wonder C (2016) Multiple cause of death data on CDC WONDER. In. Atlanta, GA US Department of Health and Human Services.

  RESULT

• Xie JY, Herman DS, Stiller CO, Gardell LR, Ossipov MH, Lai J, Porreca F, Vanderah TW. Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance. J Neurosci. 2005 Jan 12;25(2):409-16. doi: 10.1523/JNEUROSCI.4054-04.2005.

  PMID: 15647484 RESULT

• Yadav D, Park WG, Fogel EL, Li L, Chari ST, Feng Z, Fisher WE, Forsmark CE, Jeon CY, Habtezion A, Hart PA, Hughes SJ, Othman MO, Rinaudo JAS, Pandol SJ, Tirkes T, Serrano J, Srivastava S, Van Den Eeden SK, Whitcomb DC, Topazian M, Conwell DL; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas. 2018 Nov/Dec;47(10):1229-1238. doi: 10.1097/MPA.0000000000001170.

  PMID: 30325862 RESULT

• Yang AL, Vadhavkar S, Singh G, Omary MB. Epidemiology of alcohol-related liver and pancreatic disease in the United States. Arch Intern Med. 2008 Mar 24;168(6):649-56. doi: 10.1001/archinte.168.6.649.

  PMID: 18362258 RESULT

• Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer Res. 2016 Sep 1;22(17):4291-301. doi: 10.1158/1078-0432.CCR-16-0592. Epub 2016 Jul 12.

  PMID: 27407096 RESULT

• Yuan Y, Lin R, Li D, Nie L, Warren KE. Time-to-Event Bayesian Optimal Interval Design to Accelerate Phase I Trials. Clin Cancer Res. 2018 Oct 15;24(20):4921-4930. doi: 10.1158/1078-0432.CCR-18-0246. Epub 2018 May 16.

  PMID: 29769209 RESULT

• Fogel EL, Easler JJ, Yuan Y, Yadav D, Conwell DL, Vege SS, Han SY, Park W, Patrick V, White FA. Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical Trial to Determine Safety and Identify Side Effects. JMIR Res Protoc. 2024 Mar 7;13:e50513. doi: 10.2196/50513.

  PMID: 38451604 DERIVED

MeSH Terms

Conditions

Chronic Pain; Pancreatitis, Chronic; Hyperalgesia; Opioid-Related Disorders; Pancreatitis; Pain; Pancreatic Diseases; Digestive System Diseases

Interventions

Lacosamide

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Chronic Disease; Disease Attributes; Pathologic Processes; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids

Study Officials

• Aynur Unalp-Arida, MD, PhD

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

  STUDY DIRECTOR

Central Study Contacts

Evan L Fogel, MD, MSc

CONTACT

317-944-2816; efogel@iu.edu

Fletcher A White, MS, PhD

CONTACT

317-274-5164; fawhite@iu.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Stuart Sherman Professor in Gastroenterology & Hepatology, Lehman, Bucksot and Sherman Section of Pancreatobiliary Endoscopy Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: November 3, 2022
• Study Start: March 17, 2023
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: March 5, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available at the close of the study and for 5 years subsequent.
• Access Criteria: Individual requests for data sharing can be made to: efogel@iu.edu

Locations

US (5)