Functional Magnetic Resonance Imaging of Opioid Withdrawal in Healthy Human Volunteers

NCT01006707 | Completed Results

• 1 other identifier: SU-10212009-4200
• Study Type: interventional
• Target: 15
• 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. 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.

Conditions

Substance-Related Disorders

Outcome Measures

Primary Outcomes (1)

• Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration

  Changes are reporting using Spearman's correlation coefficient, using within-subject factors of time (pre-naloxone, post-naloxone) and pre-treatment (placebo, ondansetron). Changes in Objective Opioid Withdrawal Scale (OOWS) and Subjective Opioid Withdrawal Scale (SOWS) with correlation coefficient \>0.45 are reported. The OOWS consists of 13 observable physical symptoms assessed over a 5-minute observation period and scored as present (score of 1) or absent (score of 0). The total OOWS scores is determined by summing the scores of the 13 items. OOWS scores can range from 0 to 13; lower scores correspond to fewer symptoms. SOWS consists of 16 physical and emotional symptoms rated by the participant on a scale from 0 (not at all) to 4 (extremely), to indicate the extent to which the symptom describes how they are feeling at the time. The total SOWS score is determined by summing the scores of the 16 items. Scores range from 0 to 64; lower scores correspond to fewer symptoms.

  36 minutes

Secondary Outcomes (3)

• Objective Opioid Withdrawal Scale Score 5 Minutes Following Ondansetron or Placebo Administration

  5 Minutes Following Ondansetron or Placebo Administration

• Objective Opioid Withdrawal Scale Score 15 Minutes Following Ondansetron or Placebo Administration

  15 Minutes Following Ondansetron or Placebo Administration

• Subjective Opioid Withdrawal Scale (SOWS) Score 20 Minutes Following Ondansetron or Placebo Administration

  20 minutes following Ondansetron or Placebo administration

Study Arms (2)

Ondansetron, then Placebo

OTHER

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

Drug: Ondansetron

Placebo, then Ondansetron

OTHER

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

Drug: Ondansetron

Interventions

Ondansetron 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.

Also known as: Zofran

Ondansetron, then Placebo; Placebo, then Ondansetron

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (9)

• 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.

  PMID: 14751453 BACKGROUND

• 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.

  PMID: 14636819 BACKGROUND

• 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.

  PMID: 9699686 BACKGROUND

• 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.

  PMID: 7762544 BACKGROUND

• 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.

  PMID: 17602127 BACKGROUND

• 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.

  PMID: 8799580 BACKGROUND

• 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.

  PMID: 9537805 BACKGROUND

• 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.

  PMID: 12377164 BACKGROUND

• 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.

  PMID: 26059463 RESULT

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Ondansetron

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Opioid withdrawal model not necessarily generalizable to individuals with chronic pain and chronic opioid usage; short duration of scan; potential physiological noise in data; unable to obtain strong assessments of OOWS and SOWS during the scan.

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: No
• 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: Associate Professor of Anesthesia

Study Record Dates

• First Submitted: October 30, 2009
• First Posted: November 3, 2009
• Study Start: November 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: November 17, 2017
• Results First Posted: November 17, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)