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Functional Magnetic Resonance Imaging of Opioid Withdrawal in Healthy Human Volunteers

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01006707
First Posted: November 3, 2009
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Larry Fu-nien Chu, Stanford University
  Purpose
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.

Condition Intervention
Substance-Related Disorders Drug: Ondansetron

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: fMRI Imaging of Opioid Withdrawal in Healthy Human Volunteers

Resource links provided by NLM:


Further study details as provided by Larry Fu-nien Chu, Stanford University:

Primary Outcome Measures:
  • Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration [ Time Frame: 36 minutes ]
    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.


Secondary Outcome Measures:
  • Objective Opioid Withdrawal Scale Score 5 Minutes Following Ondansetron or Placebo Administration [ Time Frame: 5 Minutes Following Ondansetron or Placebo Administration ]
    The OOWS consists of 13 observable physical symptoms that are assessed over a five-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 a low of 0 to a high of 13. A score of 0 would suggest that no objective signs of withdrawal were observed while a score of 13 would suggest that every observable sign of withdrawal was observed.

  • Objective Opioid Withdrawal Scale Score 15 Minutes Following Ondansetron or Placebo Administration [ Time Frame: 15 Minutes Following Ondansetron or Placebo Administration ]
    The OOWS consists of 13 observable physical symptoms that are assessed over a five-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 a low of 0 to a high of 13. A score of 0 would suggest that no objective signs of withdrawal were observed while a score of 13 would suggest that every observable sign of withdrawal was observed.

  • Subjective Opioid Withdrawal Scale (SOWS) Score 20 Minutes Following Ondansetron or Placebo Administration [ Time Frame: 20 minutes following Ondansetron or Placebo administration ]
    The SOWS consists of 16 physical and emotional symptoms that are 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 a low of 0 to a high of 64. A score of 0 would suggest that the individual is experiencing no symptoms of withdrawal while a score of 64 would suggest that the individual is experiencing all 16 symptoms of withdrawal to the fullest extent possible.


Enrollment: 15
Study Start Date: November 2010
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Ondansetron, then Placebo
Some participants received ondansetron pretreatment during the second session, and then placebo during the third session.
Drug: 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.
Other Name: Zofran
Placebo, then Ondansetron
Some participants received placebo pretreatment during the second session, and then ondansetron pretreatment during the third session.
Drug: 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.
Other Name: Zofran

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01006707


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Dr Larry Fu-nien Chu Stanford University
  More Information

Publications:

Responsible Party: Larry Fu-nien Chu, Associate Professor of Anesthesia, Stanford University
ClinicalTrials.gov Identifier: NCT01006707     History of Changes
Other Study ID Numbers: SU-10212009-4200
First Submitted: October 30, 2009
First Posted: November 3, 2009
Results First Submitted: February 8, 2016
Results First Posted: November 17, 2017
Last Update Posted: November 17, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ondansetron
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents