Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal

Overview

Opioid medications are commonly used for pain relief. When given over time, physical dependence can occur. This results in unpleasant side effects–such as agitation and nausea–if opioid medications are suddenly stopped. We are interested in knowing if a medication named Ondansetron can help ease or prevent symptoms associated with opioid withdrawal. We are also interested in knowing if a similar (but more potent FDA-approved drug, palonosetron) can more effectively treat withdrawal symptoms with or without combination with an antihistamine called hydroxyzine (vistaril).

Full Title of Study: “Examination of Palonosetron and Hydroxyzine Pre-treatment as a Possible Method to Reduce the Objective Signs of Experimentally-induced Acute Opioid Withdrawal in Humans: a Double-blind, Randomized, Placebo-controlled Crossover Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Outcomes Assessor)
  • Study Primary Completion Date: August 2008

Detailed Description

We hope to learn if Palonosetron and/or combination with hydroxyzine can be used to prevent or attenuate the signs and symptoms of opioid withdrawal. If we find that it can help prevent these symptoms, it may become a new treatment that can aid patients suffering from these symptoms.

Interventions

  • Drug: Palonosetron
    • Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO
  • Drug: Hydroxyzine
    • Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO
  • Other: Placebo
    • Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO

Arms, Groups and Cohorts

  • Experimental: Sequence 1: Placebo, Combo, Palonosetron
    • At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Placebo Week 2: Palonosetron + Hydroxyzine Combo Week 3: Palonosetron
  • Experimental: Sequence 2: Palonosetron, Combo, Placebo
    • At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron Week 2: Palonosetron + Hydroxyzine Combo Week 3: Placebo
  • Experimental: Sequence 3: Combo, Placebo, Palonosetron
    • At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron + Hydroxyzine Combo Week 2: Placebo Week 3: Palonosetron
  • Experimental: Sequence 4: Placebo, Palonosetron, Combo
    • At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Placebo Week 2: Palonosetron only Week 3: Palonosetron + Hydroxyzine Combo
  • Experimental: Sequence 5: Combo, Palonosetron, Placebo
    • At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron + Hydroxyzine Combo Week 2: Palonosetron only Week 3: Placebo
  • Experimental: Sequence 6: Palonosetron, Placebo, Combo
    • At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron only Week 2: Placebo Week 3:Palonosetron + Hydroxyzine Combo

Clinical Trial Outcome Measures

Primary Measures

  • OOWS Score
    • Time Frame: Change from baseline in OOWS score at 180 minutes (15 minutes post naloxone administration)
    • The OOWS is a 13-item instrument documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. Maximum score possible = 13, minimum score possible = 0. T=15 minutes post naloxone administration coordinates with T = 180 (min) for the entire study session. OOWS scores at T=180 is the primary outcome measure of the study compared with baseline OOWS scores at T=-30 (30 minutes prior to study medication administration). Reported time frames are in relation to time past since administration of study medications. Mean post-Naloxone OOWS scores (+/- SEM) were determined for pretreatment groups

Secondary Measures

  • SOWS Score
    • Time Frame: Change from baseline in SOWS score at 180 minutes (15 minutes post naloxone administration)
    • The SOWS score is composed of 16 subjective symptoms rated on a scale of 0 to 4 (0=not at all, 4=extremely) based on what subjects were experiencing at the time of testing. 15 minutes post naloxone administration coordinates with T = 180 (min) for the entire study session. The highest score possible (64) would indicate that the individual was experiencing every symptom of opioid withdrawal to the fullest extent possible while the lowest score (0) would indicate that the individual was not experiencing any symptoms of opioid withdrawal. Mean post-naloxone SOWS scores (+/- SEM) were computed for pretreatment groups: Placebo, palonosetron, and palonosetron with hydroxyzine

Participating in This Clinical Trial

Inclusion Criteria

  • Healthy males – Ages 18-35 – No allergies to morphine or palonosetron – No history of addiction or substance abuse Exclusion Criteria:
  • Female – Younger than 18 or older than 35 – History of substance abuse – Raynaud's disease or coronary artery disease – Allergies to morphine or palonosetron
  • Gender Eligibility: Male

    Minimum Age: 18 Years

    Maximum Age: 35 Years

    Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

    Investigator Details

    • Lead Sponsor
      • Stanford University
    • Provider of Information About this Clinical Study
      • Principal Investigator: Larry Fu-nien Chu, Professor of Anesthesia – Stanford University
    • Overall Official(s)
      • Dr Larry Fu-nien Chu, Principal Investigator, Stanford University

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