Clinical trial NCT03777956: The Effect of Lacosamide in Peripheral Neuropathic Pain
Official title: The Effect of Lacosamide in Peripheral Neuropathic Pain: a Randomized, Double-blind, Placebo Controlled, Phenotype-stratified Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neuropathic Pain
Neuropathy;Peripheral
Neuropathy, Painful
Neuropathy, Diabetic
Neuropathy
Lead sponsor: Danish Pain Research Center
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
First posted: 2018-12-19
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to compare the change in pain intensity during treatment with a sodium-channel blocker (lacosamide) in patients with peripheral neuropathic pain with and without the irritable nociceptor phenotype.

Detailed description: The main purpose of this study is to compare the change in pain intensity during treatment with a sodium-channel blocker (lacosamide) in patients with peripheral neuropathic pain with and without the irritable nociceptor phenotype. As this is a mechanistic study, the main purpose is to compare the change in pain intensity in patients who receive an expected sufficiently effective dose of lacosamide. As supportive evidence for a drug-specific predictive biomarker, the purpose is also to compare the change in pain intensity during lacosamide vs. placebo for the two phenotypes.

We hypothesize that the sodium-channel blocker lacosamide will be more effective in patients with the irritable nociceptor than those without the non-irritable nociceptor phenotype, and that lacosamide is more effective than placebo in patients with the irritable nociceptor phenotype.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years.
2. Probable or definite peripheral neuropathic pain for at least 3 months (Finnerup et al. 2016)
3. Average pain intensity of at least 4 and not above 9 on a 0-10 NRS during the 7-day baseline week (Dworkin et al. 2012).
4. Written informed consent.

Exclusion Criteria:

1. Other causes of pain in the same area, or other concomitant pain that cannot be distinguished from the neuropathic pain
2. Patient who cannot cooperate or are unable to complete the project and patients who do not speak Danish.
3. Known and current cardiac conduction disturbance (2⁰ or 3⁰ atrioventricular (AV) block, prolonged QTc interval \> 450 ms, heart rate \<50 or \>110 bpm, a QRS interval \>120ms (ECG required)), significant cardiac, renal or liver disease or other severe illness. In patients treated with pregabalin also PQ interval \> 0,2s and cardiac disease. Sitting diastolic blood pressure below 50 mmHg or above 105 mmHg.
4. Major depressive episode within 6 months, recurrent depressive disorder or other significant psychiatric disease, alcohol, illicit drug or drug abuse.
5. Pregnancy or lactation
6. Woman of childbearing potential, unless they use and acceptable effective contraception measure as defined in the Clinical Trials Facilitation Group (CTFG) during the study and at least 2 weeks after, or if their male partner is vasectomized and their sole partners. Negative pregnancy test is required.
7. Known allergy to lacosamide or excipients.
8. Concomitant pain treatment with tricyclic antidepressants, topical analgesics (lidocaine, capsaicin), lamotrigine, oxcarbazepine, cannabinoids or strong opioids that cannot be discontinued. Other treatment for neuropathic pain are allowed in a stable dose (from 14 days before randomization to completion of the trial), if they cannot be tapered off completely.
9. Concomitant treatment with products known to be associated with PQ (PR) prolongation other than pregabalin.
10. Patients inappropriate for placebo
11. Planned surgery
12. Use of sodium channel blockers within at least five half-lives and investigational drugs within 30 days.
13. Patients on controlled sodium diet, unless the amount of sodium in the capsules is acceptable for their diet.
14. The score "yes" on item 4 or item 5 of the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS), if the ideation occurred in the past 6 months, or "yes on any item of the Suicidal Behaviour section, except for the "Non-suicidal Self Injurious Behaviour" if this behaviour occurred in the past 2 years.

Primary outcomes:
measure: Pain intensity
timeFrame: 12 weeks
Secondary outcomes:
measure: Pain relief
timeFrame: 12 weeks
measure: Use of escape medicine (paracetamol) during treatment period.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Danish Pain Research Center, Aarhus University Hospital
Study officials:
affiliation: Danish Pain Research Center
name: Nanna B Finnerup, Professor
role: STUDY_DIRECTOR
References:
citation: Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.
citation: Dworkin RH, Turk DC, Peirce-Sandner S, Burke LB, Farrar JT, Gilron I, Jensen MP, Katz NP, Raja SN, Rappaport BA, Rowbotham MC, Backonja MM, Baron R, Bellamy N, Bhagwagar Z, Costello A, Cowan P, Fang WC, Hertz S, Jay GW, Junor R, Kerns RD, Kerwin R, Kopecky EA, Lissin D, Malamut R, Markman JD, McDermott MP, Munera C, Porter L, Rauschkolb C, Rice ASC, Sampaio C, Skljarevski V, Sommerville K, Stacey BR, Steigerwald I, Tobias J, Trentacosti AM, Wasan AD, Wells GA, Williams J, Witter J, Ziegler D. Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations. Pain. 2012 Jun;153(6):1148-1158. doi: 10.1016/j.pain.2012.03.003. Epub 2012 Apr 9.
citation: Carmland ME, Kreutzfeldt M, Holbech JV, Andersen NT, Jensen TS, Bach FW, Sindrup SH, Finnerup NB. Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial. Trials. 2019 Oct 11;20(1):588. doi: 10.1186/s13063-019-3695-7.