Clinical trial NCT01006707: Functional Magnetic Resonance Imaging of Opioid Withdrawal in Healthy Human Volunteers
Official title: fMRI Imaging of Opioid Withdrawal in Healthy Human Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Substance-Related Disorders
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2009-11-03
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration
timeFrame: 36 minutes
Secondary outcomes:
measure: Objective Opioid Withdrawal Scale Score 5 Minutes Following Ondansetron or Placebo Administration
timeFrame: 5 Minutes Following Ondansetron or Placebo Administration
measure: Objective Opioid Withdrawal Scale Score 15 Minutes Following Ondansetron or Placebo Administration
timeFrame: 15 Minutes Following Ondansetron or Placebo Administration
measure: Subjective Opioid Withdrawal Scale (SOWS) Score 20 Minutes Following Ondansetron or Placebo Administration
timeFrame: 20 minutes following Ondansetron or Placebo administration
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Dr Larry Fu-nien Chu
role: PRINCIPAL_INVESTIGATOR
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citation: 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.