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Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Larry Fu-nien Chu, Stanford University
ClinicalTrials.gov Identifier:
NCT00661674
First received: April 15, 2008
Last updated: April 25, 2017
Last verified: April 2017
  Purpose
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).

Condition Intervention
Substance-Related Disorders Drug: Palonosetron Drug: Hydroxyzine Other: Placebo

Study Type: Interventional
Study Design: 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: Participant, Care Provider, Outcomes Assessor
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Larry Fu-nien Chu, Stanford University:

Primary Outcome 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 Outcome 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



Enrollment: 10
Study Start Date: April 2008
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
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

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
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

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
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

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
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

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
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

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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00661674

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Dr Larry Fu-nien Chu Stanford University
  More Information

Publications:

Study Data/Documents: Published Manuscript  This link exits the ClinicalTrials.gov site
Identifier: PMID: 27712113
Link to the manuscript which was published in The American Journal of Drug and Alcohol Abuse

Responsible Party: Larry Fu-nien Chu, Professor of Anesthesia, Stanford University
ClinicalTrials.gov Identifier: NCT00661674     History of Changes
Other Study ID Numbers: SU-04152008-1099
Study First Received: April 15, 2008
Results First Received: February 8, 2016
Last Updated: April 25, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Larry Fu-nien Chu, Stanford University:
Palonosetron
Hydroxyzine
Acute opioid withdrawal

Additional relevant MeSH terms:
Substance-Related Disorders
Substance Withdrawal Syndrome
Chemically-Induced Disorders
Mental Disorders
Analgesics, Opioid
Palonosetron
Hydroxyzine
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipruritics
Dermatologic Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents

ClinicalTrials.gov processed this record on June 22, 2017