AzTrials
AzTrials

Substance-Related DisordersNCT00661674

Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal

A study testing Palonosetron and Hydroxyzine in people with Substance-Related Disorders, run by Stanford University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 35 years, men onlyHealthy volunteers can take part
Conditions the study is for
Substance-Related Disorders
What is being tested?
Palonosetron and Hydroxyzine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
10 participants
Where
1 siteUnited States
Study dates
Apr 2008to Aug 2008
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

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

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).

Read the 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.

Being tested
Palonosetron, Hydroxyzine, Placebo
Keywords
Palonosetron, Hydroxyzine, Acute opioid withdrawal
Medical subject headings
Substance-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PalonosetronDrug

    Also called Aloxi

    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

  • HydroxyzineDrug

    Also called Vistaril, Atarax

    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

  • PlaceboOther

    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 groups in NCT00661674
Study groupRoleWhat they receive
Sequence 1: Placebo, Combo, PalonosetronExperimentalAt 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
Receives: Drug: Palonosetron; Drug: Hydroxyzine; Other: Placebo
Sequence 2: Palonosetron, Combo, PlaceboExperimentalAt 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
Receives: Drug: Palonosetron; Drug: Hydroxyzine; Other: Placebo
Sequence 3: Combo, Placebo, PalonosetronExperimentalAt 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
Receives: Drug: Palonosetron; Drug: Hydroxyzine; Other: Placebo
Sequence 4: Placebo, Palonosetron, ComboExperimentalAt 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
Receives: Drug: Palonosetron; Drug: Hydroxyzine; Other: Placebo
Sequence 5: Combo, Palonosetron, PlaceboExperimentalAt 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
Receives: Drug: Palonosetron; Drug: Hydroxyzine; Other: Placebo
Sequence 6: Palonosetron, Placebo, ComboExperimentalAt 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
Receives: Drug: Palonosetron; Drug: Hydroxyzine; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (1)

  1. SOWS Score

    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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionAug 2008
  4. Study completionAug 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
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 blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00661674
Sponsor's protocol ID
SU-04152008-1099
Status last verified
Apr 2017
First submitted
15 Apr 2008
Last updated
5 Jun 2017
Data monitoring committee
No
Individual data sharing
No

Publications

  • Committee on Advancing Pain Research Care and Education, Board on Health Sciences Policy, Institute of Medicine. A call for cultural transformation of attitudes toward pain and its prevention and management. J Pain Palliat Care Pharmacother. 2011;25(4):365-9. doi: 10.3109/15360288.2011.621516.

    PubMed 22126167

  • Kuehn BM. Opioid prescriptions soar: increase in legitimate use as well as abuse. JAMA. 2007 Jan 17;297(3):249-51. doi: 10.1001/jama.297.3.249. No abstract available.

    PubMed 17227967

  • Manchikanti L, Helm S 2nd, Fellows B, Janata JW, Pampati V, Grider JS, Boswell MV. Opioid epidemic in the United States. Pain Physician. 2012 Jul;15(3 Suppl):ES9-38.

    PubMed 22786464

  • Kobinger W, Walland A. Investigations into the mechanism of the hypotensive effect of 2-(2,6-dichlorphenylamino)-2-imidazoline-HCl. Eur J Pharmacol. 1967 Dec;2(3):155-62. doi: 10.1016/0014-2999(67)90080-5. No abstract available.

    PubMed 5626889

  • Chu LF, Liang DY, Li X, Sahbaie P, D'arcy N, Liao G, Peltz G, David Clark J. From mouse to man: the 5-HT3 receptor modulates physical dependence on opioid narcotics. Pharmacogenet Genomics. 2009 Mar;19(3):193-205. doi: 10.1097/FPC.0b013e328322e73d.

    PubMed 19214139

  • Costall B, Jones BJ, Kelly ME, Naylor RJ, Onaivi ES, Tyers MB. Sites of action of ondansetron to inhibit withdrawal from drugs of abuse. Pharmacol Biochem Behav. 1990 May;36(1):97-104. doi: 10.1016/0091-3057(90)90132-2.

    PubMed 2140900

  • Gulati A, Bhargava HN. Brain and spinal cord 5-HT2 receptors of morphine-tolerant-dependent and -abstinent rats. Eur J Pharmacol. 1989 Aug 22;167(2):185-92. doi: 10.1016/0014-2999(89)90578-5.

    PubMed 2591474

  • Tao R, Ma Z, Auerbach SB. Alteration in regulation of serotonin release in rat dorsal raphe nucleus after prolonged exposure to morphine. J Pharmacol Exp Ther. 1998 Jul;286(1):481-8.

    PubMed 9655893

  • Ingram SL, Vaughan CW, Bagley EE, Connor M, Christie MJ. Enhanced opioid efficacy in opioid dependence is caused by an altered signal transduction pathway. J Neurosci. 1998 Dec 15;18(24):10269-76. doi: 10.1523/JNEUROSCI.18-24-10269.1998.

    PubMed 9852564

  • Tao R, Auerbach SB. Involvement of the dorsal raphe but not median raphe nucleus in morphine-induced increases in serotonin release in the rat forebrain. Neuroscience. 1995 Sep;68(2):553-61. doi: 10.1016/0306-4522(95)00154-b.

    PubMed 7477965

  • Pinelli A, Trivulzio S, Tomasoni L. Effects of ondansetron administration on opioid withdrawal syndrome observed in rats. Eur J Pharmacol. 1997 Dec 11;340(2-3):111-9. doi: 10.1016/s0014-2999(97)01349-6.

    PubMed 9537805

  • Smith HS, Cox LR, Smith EJ. 5-HT3 receptor antagonists for the treatment of nausea/vomiting. Ann Palliat Med. 2012 Jul;1(2):115-20. doi: 10.3978/j.issn.2224-5820.2012.07.07.

    PubMed 25841471

  • Compton P, Miotto K, Elashoff D. Precipitated opioid withdrawal across acute physical dependence induction methods. Pharmacol Biochem Behav. 2004 Feb;77(2):263-8. doi: 10.1016/j.pbb.2003.10.017.

    PubMed 14751453

  • Grunberg SM, Koeller JM. Palonosetron: a unique 5-HT3-receptor antagonist for the prevention of chemotherapy-induced emesis. Expert Opin Pharmacother. 2003 Dec;4(12):2297-303. doi: 10.1517/14656566.4.12.2297.

    PubMed 14640928

  • Mustian KM, Devine K, Ryan JL, Janelsins MC, Sprod LK, Peppone LJ, Candelario GD, Mohile SG, Morrow GR. Treatment of Nausea and Vomiting During Chemotherapy. US Oncol Hematol. 2011;7(2):91-97. doi: 10.17925/ohr.2011.07.2.91.

    PubMed 24466408

Questions about this trial

What is this clinical trial studying?

A study testing Palonosetron and Hydroxyzine in people with Substance-Related Disorders, run by Stanford University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

OOWS Score (time frame: Change from baseline in OOWS score at 180 minutes (15 minutes post naloxone administration)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00661674, which also lists 33 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in