Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal

NCT00661674 | Completed Results

• 1 other identifier: SU-04152008-1099
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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).

Conditions

Substance-Related Disorders

Keywords

Palonosetron; Hydroxyzine; Acute opioid withdrawal

Outcome Measures

Primary Outcomes (1)

• OOWS Score

  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

  Change from baseline in OOWS score at 180 minutes (15 minutes post naloxone administration)

Secondary Outcomes (1)

• SOWS Score

  Change from baseline in SOWS score at 180 minutes (15 minutes post naloxone administration)

Study Arms (6)

Sequence 1: Placebo, Combo, Palonosetron

EXPERIMENTAL

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; Drug: Hydroxyzine; Other: Placebo

Sequence 2: Palonosetron, Combo, Placebo

EXPERIMENTAL

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; Drug: Hydroxyzine; Other: Placebo

Sequence 3: Combo, Placebo, Palonosetron

EXPERIMENTAL

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; Drug: Hydroxyzine; Other: Placebo

Sequence 4: Placebo, Palonosetron, Combo

EXPERIMENTAL

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; Drug: Hydroxyzine; Other: Placebo

Sequence 5: Combo, Palonosetron, Placebo

EXPERIMENTAL

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; Drug: Hydroxyzine; Other: Placebo

Sequence 6: Palonosetron, Placebo, Combo

EXPERIMENTAL

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; Drug: Hydroxyzine; Other: Placebo

Interventions

Palonosetron DRUG

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

Also known as: Aloxi

Sequence 1: Placebo, Combo, Palonosetron; Sequence 2: Palonosetron, Combo, Placebo; Sequence 3: Combo, Placebo, Palonosetron; Sequence 4: Placebo, Palonosetron, Combo; Sequence 5: Combo, Palonosetron, Placebo; Sequence 6: Palonosetron, Placebo, Combo

Hydroxyzine DRUG

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

Also known as: Vistaril, Atarax

Sequence 1: Placebo, Combo, Palonosetron; Sequence 2: Palonosetron, Combo, Placebo; Sequence 3: Combo, Placebo, Palonosetron; Sequence 4: Placebo, Palonosetron, Combo; Sequence 5: Combo, Palonosetron, Placebo; Sequence 6: Palonosetron, Placebo, Combo

Placebo OTHER

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

Sequence 1: Placebo, Combo, Palonosetron; Sequence 2: Palonosetron, Combo, Placebo; Sequence 3: Combo, Placebo, Palonosetron; Sequence 4: Placebo, Palonosetron, Combo; Sequence 5: Combo, Palonosetron, Placebo; Sequence 6: Palonosetron, Placebo, Combo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males
• Ages 18-35
• No allergies to morphine or palonosetron
• No history of addiction or substance abuse

You may not qualify if:

• Female
• Younger than 18 or older than 35
• History of substance abuse
• Raynaud's disease or coronary artery disease
• Allergies to morphine or palonosetron

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

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MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Palonosetron; Hydroxyzine

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Results are not necessarily generalizable to patients with chronic opioid exposure.

Results Point of Contact

• Title: Dr. Larry Chu
• Organization: Stanford University School of Medicine

lchu@stanford.edu

(650) 723-6632

Study Officials

• Dr Larry Fu-nien Chu

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesia

Model Details: 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

Study Record Dates

• First Submitted: April 15, 2008
• First Posted: April 18, 2008
• Study Start: April 1, 2008
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: June 5, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)