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NCT Number: NCT04603066

Tariquidar-ondansetron Combination in Neuropathic Pain

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.

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Key information

Conditions

Neuropathic Pain Nervous System Diseases Neuralgia Neurologic Manifestations Neuromuscular Diseases Pain Pathological Conditions, Signs and Symptoms Peripheral Nervous System Diseases Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Washington University School of Medicine/Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

About this study

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:

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Current pregnancy or lactation;
  • Moderate-severe kidney or liver dysfunction;
  • Active cardiac arrhythmias (non-sinus rhythm), Long QT syndrome, or QTc interval >450msec;
  • Congestive heart failure
  • Abnormal troponin values at screening visit;
  • Current treatment with MAO inhibitors, mirtazapine, SSRI antidepressants, or SNRI medications duloxetine or venlafaxine;
  • Current treatment with tapentadol, tramadol, or fentanyl;
  • Current treatment with P-glycoprotein substrate drugs with narrow therapeutic window, e.g. digoxin;
  • Current treatment with tricyclic antidepressant medications (e.g. amitriptyline, desipramine, imipramine) at a dose >25mg/day;
  • 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;
  • 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.);
  • Current treatment with anticoagulant drugs;

Treatment and study plan

Ondansetron 16 mg with Tariquidar

Drug

In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.

Other names: Ondansetron/Tariquidar

Ondansetron 16 mg with Placebo

Drug

In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.

Other names: Ondansetron/ Placebo

Primary outcomes

  1. Concertation-time Profile of Ondansetron in Plasma, Measured by the Area Under the Concentration-time Curve (AUC)

    Time frame: Measurements over 240 minutes, extrapolated to infinity

    AUCinf for Ondansetron concentration in plasma based on venous blood sampling for plasma concentrations of ondansetron obtained at 0, 15, 30, 60, 90, 120, 180, and 240 minutes from the beginning of ondansetron infusion.

  2. Cerebrospinal Fluid to Plasma Concentration Ratio of Ondansetron

    Time frame: anytime between 0-240 minutes

    The level of ondansetron in plasma and CSF (cerebrospinal fluid) in samples, taken around the same time, was measured, and the ratio of the two values was calculated. This ratio (partition coefficient, Kp) of ondansetron, compared between the two sessions, with placebo vs tariquidar

Secondary outcomes

  1. % Change in Pain Intensity

    Time frame: baseline to 90 minutes after ondansetron IV infusion

    Change in spontaneous pain intensity (measured on a 0-10 numerical rating scale; 0=no pain, 10=worst imaginable pain) from baseline to 90 minutes after ondansetron IV infusion, compared between two sessions with and without tariquidar. Values are presented as a percentage change from baseline.

  2. Conditioned Pain Modulation (CPM) Magnitude (ΔCPM)

    Time frame: Baseline and 90 minutes after the end of ondansetron infusion

    Conditioned Pain Modulation (CPM) is a psychophysical test to assess the efficiency of descending pain inhibition. CPM is calculated as difference in heat pain threshold with and without pain conditioning - i.e. immersion of a hand in cold water. Conditioned Pain Modulation (CPM) Negative CPM values represent efficient pain modulation/inhibition.

    This test was administered at baseline, and again 90-min after the end of ondansetron infusion. CPM values can range from -100 to 100, CPM<0 (i.e. decreased pain to heat stimulus following conditioning) implies descending pain inhibition.

    CPM Magnitude (ΔCPM) is the calculated by subtracting the measurement of CPM at baseline [possible range of CPM scores 0-100] from the measurement of CPM 90 min after the intervention [possible range of CPM scores 0-100]. A larger negative ΔCPM value indicates increased pain modulation efficiency following treatment, and therefore, a desired outcome.

  3. Correlation Between CPM Magnitude (ΔCPM) and Change in Pain Intensity

    Time frame: 0-240 min from infusion

    The association between baseline Conditioned Pain Modulation (CPM) magnitude (ΔCPM) and the % pain reduction from baseline will be determined by bivariate regression.

  4. Change in Neuropathic Pain Symptom Inventory (NPSI) Score

    Time frame: baseline to 70 min after infusion

    Changes in the Neuropathic Pain Symptom Inventory (NPSI) total score will be compared between treatment sessions.

    NPSI is a questionnaire used to assess and quantify neuropathic pain by asking patients to rate the severity of different pain sensations on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable. The version administered in the study consists of seven questions, each rated on a scale from 0 to 10, with the total score being the sum of all ratings.

    The possible range of the NPSI score of the version administered in the study is 70, and, since we measure the difference in scores, the changes in the NPSI score of the version administered in the study is -70 to 70. Higher NPSI scores indicate more severe neuropathic pain symptoms. Since the analysis is conducted on changes in NPSI scores from baseline, a more negative value corresponds to a greater reduction in neuropathic pain symptoms following treatment.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Registry information

Official study title

Administration of Ondansetron With P-glycoprotein Inhibitor Tariquidar in Patients With Neuropathic Pain

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Oct 26, 2020
Registry last updated
Aug 14, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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