Clinical trial NCT04603066: Tariquidar-ondansetron Combination in Neuropathic Pain
Official title: Administration of Ondansetron With P-glycoprotein Inhibitor Tariquidar in Patients With Neuropathic Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neuropathic Pain
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2020-10-26
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Prospective, randomized, double blind, crossover study
Primary purpose: TREATMENT

Brief summary: Prospective, randomized, double-blind, placebo controlled, cross-over proof of concept study.

To determine the pharmacokinetics and tolerability of co-administration of 5-HT3R antagonist ondansetron with a P-glycoprotein inhibitor tariquidar, in patients with neuropathic pain.

Detailed description: The investigators hypothesize that co-administration of a 5-HT3 receptor antagonist ondansetron (single 16mg dose) with p-glycoprotein inhibitor tariquidar (single 4mg/kg dose) vs placebo in a cross-over prospective randomized study, will:

1. Be tolerable in patients with neuropathic pain.
2. Increase the cerebrospinal fluid (CSF) to plasma ratio of ondansetron after intravenous administration, compare to ondansetron alone
3. Result in a greater reduction in pain intensity than with ondansetron alone.

Eligibility criteria: Inclusion Criteria:

1. Age 18-65;
2. Documented diagnosis of neuropathic pain due to damage or disease affecting the peripheral nervous system;
3. At least Probable neuropathic pain grading1;
4. Pain duration \>3 months;
5. Average pain intensity ≥4 on 0-10 numerical rating scale (NRS).

Exclusion Criteria:

1. Current pregnancy or lactation;
2. Moderate-severe kidney or liver dysfunction;
3. Active cardiac arrhythmias (non-sinus rhythm), Long QT syndrome, or QTc interval \>450msec;
4. Congestive heart failure
5. Abnormal troponin values at screening visit;
6. Current treatment with MAO inhibitors, mirtazapine, SSRI antidepressants, or SNRI medications duloxetine or venlafaxine;
7. Current treatment with tapentadol, tramadol, or fentanyl;
8. Current treatment with P-glycoprotein substrate drugs with narrow therapeutic window, e.g. digoxin;
9. Current treatment with tricyclic antidepressant medications (e.g. amitriptyline, desipramine, imipramine) at a dose \>25mg/day;
10. Ongoing use of any of the following medications with known effects on Pgp function: carbamazepine, phenytoin, phenobarbital, cyclosporine, clarithromycin, erythromycin, ritonavir, verapamil, rifampicin, St. John's wort;
11. Current treatment with QT-prolonging drugs, and drugs known to have a significant interaction with ondansetron or other P-glycoprotein substrates (see section 2.3.3.);
12. Current treatment with anticoagulant drugs;

Primary outcomes:
measure: Concertation-time Profile of Ondansetron in Plasma
timeFrame: up to 8 weeks following consent
measure: Cerebrospinal Fluid to Plasma Concentration Ratio of Ondansetron
timeFrame: up to 8 weeks following consent
measure: Cerebrospinal Fluid Penetration of Ondansetron - Area Under the Curve (AUC)
timeFrame: up to 8 weeks following consent
Secondary outcomes:
measure: Change in Pain Intensity
timeFrame: up to 8 weeks following consent
measure: Conditioned Pain Modulation (CPM) Magnitude (ΔCPM)
timeFrame: up to 8 weeks following consent
measure: Correlation between CPM Magnitude (ΔCPM) and Change in Pain Intensity
timeFrame: up to 8 weeks following consent
measure: Change in Neuropathic Pain Symptom Score
timeFrame: up to 8 weeks following consent
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine/Barnes-Jewish Hospital
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Simon Haroutounian, PhD
role: PRINCIPAL_INVESTIGATOR
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: Yawn BP, Wollan PC, Weingarten TN, Watson JC, Hooten WM, Melton LJ 3rd. The prevalence of neuropathic pain: clinical evaluation compared with screening tools in a community population. Pain Med. 2009 Apr;10(3):586-93. doi: 10.1111/j.1526-4637.2009.00588.x. Epub 2009 Mar 17.
citation: Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Curr Pain Headache Rep. 2012 Jun;16(3):191-8. doi: 10.1007/s11916-012-0256-0.