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Functional Magnetic Resonance Imaging of Opioid Withdrawal in Healthy Human Volunteers

NCT ID: NCT01006707

Last Updated: 2017-11-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2013-07-31

Brief Summary

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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. However, we do not know how withdrawal affects the brain. We know that a medication named Ondansetron can help ease or prevent symptoms associated with opioid withdrawal. Through imaging of the brain by fMRI, we hope to see how opioid withdrawal, with and without the administration of ondansetron, affects brain activity.

Detailed Description

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During the study, each participant attended three separate lab-based acute opioid withdrawal sessions. The first session was undertaken in a mock MRI scanner and was designed to determine if participants could tolerate withdrawal in the scanning environment. Participants who were able to successfully and safely tolerate opioid withdrawal while in the scanner were approved to continue with the following study sessions. Participants were then pretreated intravenously (IV) with either 0.9% normal saline placebo or 8mg ondansetron. Later, participants in all sessions received IV naloxone (10mg/70kg) to precipitate opioid withdrawal. Participants were assigned to ondansetron or placebo pretreatment conditions in a randomized, double-blinded, and counter-balanced order. Objective Opioid Withdrawal Scale (OOWS) and Subjective Opioid Withdrawal Scale (SOWS) were assessed throughout the study to quantify withdrawal. Study timeline progressed as follows: T=-165, 8mg ondansetron or placebo infusion, T=-135, Morphine infusion (10mg/70kg), T=-41 preparation for MRI, T=-21, start MRI, T=-13, baseline OOWS/SOWS, T=-9, start of fMRI, T=0 Naloxone induced withdrawal, T=5, OOWS, T=15, OOWS, T=20, Retrospective OOWS.

Conditions

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Substance-Related Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Ondansetron, then Placebo

Some participants received ondansetron pretreatment during the second session, and then placebo during the third session.

Group Type OTHER

Ondansetron

Intervention Type DRUG

In this cross-over study, the blinded patient will receive saline placebo in one session and ondansetron in the other. The order is decided with a randomization table. If ondansetron is randomly chosen, an 8mg IV Bolus will be given at the start of the study for 30 minutes by the unblinded investigator.

Placebo, then Ondansetron

Some participants received placebo pretreatment during the second session, and then ondansetron pretreatment during the third session.

Group Type OTHER

Ondansetron

Intervention Type DRUG

In this cross-over study, the blinded patient will receive saline placebo in one session and ondansetron in the other. The order is decided with a randomization table. If ondansetron is randomly chosen, an 8mg IV Bolus will be given at the start of the study for 30 minutes by the unblinded investigator.

Interventions

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Ondansetron

In this cross-over study, the blinded patient will receive saline placebo in one session and ondansetron in the other. The order is decided with a randomization table. If ondansetron is randomly chosen, an 8mg IV Bolus will be given at the start of the study for 30 minutes by the unblinded investigator.

Intervention Type DRUG

Other Intervention Names

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Zofran

Eligibility Criteria

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Inclusion Criteria

* Patients will be healthy male volunteers, ages 18-35.

Exclusion Criteria

* Females were excluded due to menstrual cycle modulation of opioid response.
* We will exclude individuals with Raynaud's disease or a history of coronary artery disease.
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Larry Fu-nien Chu

Associate Professor of Anesthesia

Responsibility Role PRINCIPAL_INVESTIGATOR

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

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 14751453 (View on PubMed)

Compton P, Athanasos P, Elashoff D. Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study. J Pain. 2003 Nov;4(9):511-9. doi: 10.1016/j.jpain.2003.08.003.

Reference Type BACKGROUND
PMID: 14636819 (View on PubMed)

Stein EA, Pankiewicz J, Harsch HH, Cho JK, Fuller SA, Hoffmann RG, Hawkins M, Rao SM, Bandettini PA, Bloom AS. Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. Am J Psychiatry. 1998 Aug;155(8):1009-15. doi: 10.1176/ajp.155.8.1009.

Reference Type BACKGROUND
PMID: 9699686 (View on PubMed)

Krystal JH, Woods SW, Kosten TR, Rosen MI, Seibyl JP, van Dyck CC, Price LH, Zubal IG, Hoffer PB, Charney DS. Opiate dependence and withdrawal: preliminary assessment using single photon emission computerized tomography (SPECT). Am J Drug Alcohol Abuse. 1995 Feb;21(1):47-63. doi: 10.3109/00952999509095229.

Reference Type BACKGROUND
PMID: 7762544 (View on PubMed)

Williams TM, Daglish MR, Lingford-Hughes A, Taylor LG, Hammers A, Brooks DJ, Grasby P, Myles JS, Nutt DJ. Brain opioid receptor binding in early abstinence from opioid dependence: positron emission tomography study. Br J Psychiatry. 2007 Jul;191:63-9. doi: 10.1192/bjp.bp.106.031120.

Reference Type BACKGROUND
PMID: 17602127 (View on PubMed)

Hui SC, Sevilla EL, Ogle CW. Prevention by the 5-HT3 receptor antagonist, ondansetron, of morphine-dependence and tolerance in the rat. Br J Pharmacol. 1996 Jun;118(4):1044-50. doi: 10.1111/j.1476-5381.1996.tb15504.x.

Reference Type BACKGROUND
PMID: 8799580 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9537805 (View on PubMed)

Lowe AS, Williams SC, Symms MR, Stolerman IP, Shoaib M. Functional magnetic resonance neuroimaging of drug dependence: naloxone-precipitated morphine withdrawal. Neuroimage. 2002 Oct;17(2):902-10.

Reference Type BACKGROUND
PMID: 12377164 (View on PubMed)

Chu LF, Lin JC, Clemenson A, Encisco E, Sun J, Hoang D, Alva H, Erlendson M, Clark JD, Younger JW. Acute opioid withdrawal is associated with increased neural activity in reward-processing centers in healthy men: A functional magnetic resonance imaging study. Drug Alcohol Depend. 2015 Aug 1;153:314-22. doi: 10.1016/j.drugalcdep.2015.04.019. Epub 2015 May 27.

Reference Type RESULT
PMID: 26059463 (View on PubMed)

Other Identifiers

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SU-10212009-4200

Identifier Type: -

Identifier Source: org_study_id