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Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal

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ClinicalTrials.gov Identifier: NCT00661674
Recruitment Status : Completed
First Posted : April 18, 2008
Results First Posted : June 5, 2017
Last Update Posted : June 5, 2017
Sponsor:
Information provided by (Responsible Party):
Larry Fu-nien Chu, Stanford University

Tracking Information
First Submitted Date  ICMJE April 15, 2008
First Posted Date  ICMJE April 18, 2008
Results First Submitted Date  ICMJE February 8, 2016
Results First Posted Date  ICMJE June 5, 2017
Last Update Posted Date June 5, 2017
Study Start Date  ICMJE April 2008
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 25, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2008)
OOWS Score
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2017)
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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2008)
SOWS Score
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal
Official Title  ICMJE 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
Brief Summary 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).
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

There were three treatment arms to the study: Placebo, Palonosetron, and Palonosetron + Hydroxyzine (Combo). Participants were not randomized in between these arms, all participants completed each arm of the study in a cross-over study methodology (Placebo, Palonosetron, Palonosetron + Hydroxyzene (combo). Participants were individually randomized into the order in which they participated in each arm.

Per sequence each individual participant underwent the following randomization schedule:

Participant 1: Placebo, Combo, Palonosetron Participant 2: Palonosetron, Combo, Placebo Participant 3: Palonosetron, Combo, Placebo Participant 4: Combo, Placebo, Palonosetron Participant 5: Placebo, Palonosetron, Combo Participant 6: Combo, Palonosetron, Placebo Participant 7: Combo, Placebo, Palonosetron Participant 8: Combo, Palonosetron, Placebo Participant 9: Palonosetron, Placebo, Combo Participant 10: Placebo, Combo, Palonosetron

Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Substance-Related Disorders
Intervention  ICMJE
  • 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
    Other Name: Aloxi
  • 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 Name: Vistaril, Atarax
  • 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
Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: Palonosetron
    • Drug: Hydroxyzine
    • Other: Placebo
  • 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

    Interventions:
    • Drug: Palonosetron
    • Drug: Hydroxyzine
    • Other: 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

    Interventions:
    • Drug: Palonosetron
    • Drug: Hydroxyzine
    • Other: Placebo
  • 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

    Interventions:
    • Drug: Palonosetron
    • Drug: Hydroxyzine
    • Other: Placebo
  • 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

    Interventions:
    • Drug: Palonosetron
    • Drug: Hydroxyzine
    • Other: 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

    Interventions:
    • Drug: Palonosetron
    • Drug: Hydroxyzine
    • Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 5, 2012)
10
Original Enrollment  ICMJE
 (submitted: April 17, 2008)
14
Actual Study Completion Date  ICMJE August 2008
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00661674
Other Study ID Numbers  ICMJE SU-04152008-1099
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Larry Fu-nien Chu, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dr Larry Fu-nien Chu Stanford University
PRS Account Stanford University
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP