Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal
NCT ID: NCT00661674
Last Updated: 2017-06-05
Study Results
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View full resultsBasic Information
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COMPLETED
NA
10 participants
INTERVENTIONAL
2008-04-30
2008-08-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
CROSSOVER
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
TREATMENT
TRIPLE
Study Groups
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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Interventions
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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
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
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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Ages 18-35
* No allergies to morphine or palonosetron
* No history of addiction or substance abuse
Exclusion Criteria
* Younger than 18 or older than 35
* History of substance abuse
* Raynaud's disease or coronary artery disease
* Allergies to morphine or palonosetron
18 Years
35 Years
MALE
Yes
Sponsors
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Stanford University
OTHER
Responsible Party
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Larry Fu-nien Chu
Professor of Anesthesia
Principal Investigators
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Dr Larry Fu-nien Chu
Role: PRINCIPAL_INVESTIGATOR
Stanford University
Locations
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Stanford University School of Medicine
Stanford, California, United States
Countries
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References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Smith HS, Laufer A. Opioid induced nausea and vomiting. Eur J Pharmacol. 2014 Jan 5;722:67-78. doi: 10.1016/j.ejphar.2013.09.074. Epub 2013 Oct 21.
Mazurkiewicz-Kwilecki IM, Bielkiewicz B. The effects of chronic morphine treatment on histamine concentration and histidine decarboxylase activity in rat brain. Prog Neuropsychopharmacol. 1978;2(1):93-9. doi: 10.1016/0364-7722(78)90027-9. No abstract available.
Wong CL, Roberts MB. The possible role of brain histamine and H1 and H2 receptors in the development of morphine tolerance and physical dependence in mice. Agents Actions. 1975 Dec;5(5):476-83. doi: 10.1007/BF01972684.
Wong CL, Roberts MB. The effects of L-histidine and of specific histamine receptor agonists, on the expression of morphine tolerance and physical dependence in mice. Agents Actions. 1976 Sep;6(5):569-76. doi: 10.1007/BF01971571.
Hoehe M. Influence of the menstrual cycle on neuroendocrine and behavioral responses to an opiate agonist in humans: preliminary results. Psychoneuroendocrinology. 1988;13(4):339-44. doi: 10.1016/0306-4530(88)90059-5.
Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987;13(3):293-308. doi: 10.3109/00952998709001515.
Alsaadi SM, McAuley JH, Hush JM, Lo S, Lin CW, Williams CM, Maher CG. Poor sleep quality is strongly associated with subsequent pain intensity in patients with acute low back pain. Arthritis Rheumatol. 2014 May;66(5):1388-94. doi: 10.1002/art.38329.
Schuh-Hofer S, Wodarski R, Pfau DB, Caspani O, Magerl W, Kennedy JD, Treede RD. One night of total sleep deprivation promotes a state of generalized hyperalgesia: a surrogate pain model to study the relationship of insomnia and pain. Pain. 2013 Sep;154(9):1613-1621. doi: 10.1016/j.pain.2013.04.046. Epub 2013 May 11.
De Leon A. Palonosetron (Aloxi): a second-generation 5-HT(3) receptor antagonist for chemotherapy-induced nausea and vomiting. Proc (Bayl Univ Med Cent). 2006 Oct;19(4):413-6. doi: 10.1080/08998280.2006.11928210.
Boon JH, Hopkins D. Hydroxyzine premedication--does it provide better anxiolysis than a placebo? S Afr Med J. 1996 Jun;86(6):661-4.
Roychoudhury M, Kulkarni SK. Prevention of morphine discontinuation phenomenon in mice by ondansetron, a selective 5-HT3 antagonist. Methods Find Exp Clin Pharmacol. 1996 Dec;18(10):677-83.
Cui R, Suemaru K, Li B, Kohnomi S, Araki H. Tropisetron attenuates naloxone-induced place aversion in single-dose morphine-treated rats: role of alpha7 nicotinic receptors. Eur J Pharmacol. 2009 May 1;609(1-3):74-7. doi: 10.1016/j.ejphar.2008.12.051. Epub 2009 Jan 17.
Araki H, Kawakami KY, Jin C, Suemaru K, Kitamura Y, Nagata M, Futagami K, Shibata K, Kawasaki H, Gomita Y. Nicotine attenuates place aversion induced by naloxone in single-dose, morphine-treated rats. Psychopharmacology (Berl). 2004 Feb;171(4):398-404. doi: 10.1007/s00213-003-1595-7. Epub 2003 Sep 10.
Motoshima S, Suemaru K, Kawasaki Y, Jin C, Kawasaki H, Gomita Y, Araki H. Effects of alpha4beta2 and alpha7 nicotinic acetylcholine receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats. Eur J Pharmacol. 2005 Sep 5;519(1-2):91-5. doi: 10.1016/j.ejphar.2005.06.050.
Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science. 1991 Oct 18;254(5030):432-7. doi: 10.1126/science.1718042.
Albertson TE, Chenoweth J, Ford J, Owen K, Sutter ME. Is it prime time for alpha2-adrenocepter agonists in the treatment of withdrawal syndromes? J Med Toxicol. 2014 Dec;10(4):369-81. doi: 10.1007/s13181-014-0430-3.
Walsh SL, Strain EC, Bigelow GE. Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans. Addiction. 2003 Apr;98(4):427-39. doi: 10.1046/j.1360-0443.2003.00372.x.
Erlendson MJ, D'Arcy N, Encisco EM, Yu JJ, Rincon-Cruz L, Peltz G, Clark JD, Chu LF. Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study. Am J Drug Alcohol Abuse. 2017 Jan;43(1):78-86. doi: 10.1080/00952990.2016.1210614. Epub 2016 Aug 11.
Other Identifiers
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SU-04152008-1099
Identifier Type: -
Identifier Source: org_study_id
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