5HT3 Antagonists to Treat Opioid Withdrawal and to Prevent the Progression of Physical Dependence

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Stanford University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT01549652
First received: February 13, 2012
Last updated: March 8, 2012
Last verified: March 2012
  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. This study aims to test the use of the drug ondansetron to reduce the symptoms associated with opioid withdrawal and to prevent the progression of opioid physical dependence, thereby allowing future investigators to better test the role of physical dependence in the development of addiction and also possibly improving acceptance of abstinence-based programs for addiction.


Condition Intervention
Opioid Withdrawal
Physical Dependence
Drug: Ondansetron

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 5HT3 Antagonists to Treat Opioid Withdrawal and to Prevent the Progression of Physical Dependence

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Change in baseline of Objective Opioid Withdrawal Score [ Time Frame: Changes in baseline OOWS scores will be measured on 3 study days, over the span of 1.5 months. The baseline OOWs score is measured at T=-10 min., after Ondasetron/Placebo infusion at T=15 min., and after the Naloxone infusion at T=35 and T=45 min. ] [ Designated as safety issue: No ]
    Originally developed by Handelsman, the OOWS score is a well-characterized measure of opioid withdrawl in humans. The OOWS is a 13-item instrument documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period.


Secondary Outcome Measures:
  • Change in the Baseline of Subjective Opioid Withdrawal Score [ Time Frame: Changes in baseline SOWS scores will be measured on 3 study days, over the span of 1.5 months. The baseline SOWs score is measured at T=-10 min., after Ondasetron/Placebo infusion at T=15 min., and after the Naloxone infusion at T=35 and T=45 min. ] [ Designated as safety issue: No ]
    The SOWS score is composed of 16 subjective symptoms rated on a scale of 0 to 4 (0=not at all, 4=extremely) based on what subjects were experiencing at the time of testing.

  • Beck Depression Inventory [ Time Frame: Beck Depression Inventory is measured once at the start of each study visit, over the span of 1.5 months. ] [ Designated as safety issue: No ]
    The Beck Depression Inventory yields a single score between 0 and 63; higher scores indicate more severe depression.

  • Pain Inventory [ Time Frame: Pain inventory is measured once at the start of each study visit, over the span of 1.5 months. ] [ Designated as safety issue: No ]
    Patients will complete daily Brief Pain Inventories (Short Form), a 9-item multi-dimensional pain and functionality survey (Appendix).

  • Change in Baseline of Physical Vital Signs [ Time Frame: Changes in baseline of physical vital signs is measured over the span of 1.5 months on 3 study days. Baseline physical vital signs are measured at T=-10, after Ondasetron/Placebo infusion at T=15, and after the Naloxone infusion at T=35 and T=45. ] [ Designated as safety issue: No ]
    Heart rate, respiratory rate, and pupil diameter increases after precipitated OW will be measured. Heart rate will be monitored by EKG, and respiratory rate will be counted by direct observation over a period of thirty seconds. Pupil diameter will be measured using a research caliber digital automated pupillometer.

  • Serum Factors [ Time Frame: Serum factors are measured at the end of every study visit, over the span of 1.5 months. ] [ Designated as safety issue: No ]
    Serum cortisol and adrenocorticotropic hormone levels will also be tested as measures of withdrawal, as these have been shown to increase in the setting of opioid withdrawal and have even preceded physical signs of withdrawal according to a single case report. Blood without additives will be collected in a plain tube (5 mL) and serum (2 mL) will be sent to Stanford University laboratories for serum immunoassay of cortisol levels. Additional blood will be collected into a lavender top (EDTA) tube and sent to Stanford University laboratories for adrenocorticotropic hormone testing.

  • Pain Sensitivity [ Time Frame: Changes in baseline of pain sensitivity are measured over the span of 1.5 months on 3 study days. Baseline pain sensitivity is measured at T=-10, after the Ondasetron/Placebo infusion at T=15, and after the Naloxone infusion at T=35 and T=45 ] [ Designated as safety issue: No ]
    We will measure cold pressor pain as another measure of physical dependency that may change with ondansetron treatment.


Estimated Enrollment: 133
Study Start Date: April 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prevention of Physical Dependence Drug: Ondansetron

Prevention of Physical Dependence: After 1 month of oral morphine therapy, patients will go to the Stanford human opioid physiology lab for opioid withdrawal testing for Visit #1. Patients will be randomized in a double-blind fashion to treatment crossover assignments (placebo vs. 32 mg ondansetron) that will be conducted on 2 separate visits at least 1 week apart. Patients will continue to take oral morphine therapy until both study visits are complete.

Treatment of Opioid Withdrawal: Patients will be randomized into 2 groups: control arm (placebo) or prevention arm (8 mg ondansetron). Patients will go to the Stanford human opioid physiology lab for opioid withdrawal testing for Visit #1. After Visit #1, patients will undergo 1 month of oral morphine therapy. Patients will be instructed to take a treatment pill (placebo vs. ondansetron) with each dose of morphine. Then, patients will return to the Stanford human opioid physiology lab for Visit #2, which will be identical to Visit #1.

Other Name: Zofran
Experimental: Treatment of Opioid Withdrawal Drug: Ondansetron

Prevention of Physical Dependence: After 1 month of oral morphine therapy, patients will go to the Stanford human opioid physiology lab for opioid withdrawal testing for Visit #1. Patients will be randomized in a double-blind fashion to treatment crossover assignments (placebo vs. 32 mg ondansetron) that will be conducted on 2 separate visits at least 1 week apart. Patients will continue to take oral morphine therapy until both study visits are complete.

Treatment of Opioid Withdrawal: Patients will be randomized into 2 groups: control arm (placebo) or prevention arm (8 mg ondansetron). Patients will go to the Stanford human opioid physiology lab for opioid withdrawal testing for Visit #1. After Visit #1, patients will undergo 1 month of oral morphine therapy. Patients will be instructed to take a treatment pill (placebo vs. ondansetron) with each dose of morphine. Then, patients will return to the Stanford human opioid physiology lab for Visit #2, which will be identical to Visit #1.

Other Name: Zofran

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of chronic low-back pain and who may be taking up to 30 mg equivalent of morphine per day (such as Vicodin, Percocet, etc)
  • 18-60 years old
  • Eligible to escalate opioid therapy dose, as determined by the treating physician or PI
  • At low risk for addiction as determined by the PI and an addiction expert, Dr. Ian Carroll.

Exclusion Criteria:

  • History of cardiovascular disease
  • History of peripheral neuropathic pain, scleroderma, or other condition that would preclude cold water forearm immersion
  • History of addiction or chronic pain conditions other than low-back pain, d) history of cardiac arrhythmia
  • History of hepatic disease
  • Use of steroid or nerve-stimulating medications
  • Any condition precluding opioid use
  • Pregnancy
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01549652

Contacts
Contact: Larry F Chu, MD, MS (650) 724-2970 lchu@stanford.edu
Contact: John S Sun, BS (650)887-4677 johnjsun@gmail.com

Locations
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Larry Chu, MD, MS    650-724-2970    lchu@stanford.edu   
Contact: John Sun, BS    (650) 887 - 4677    johnjsun@gmail.com   
Principal Investigator: Larry F Chu, MD, MS         
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Larry F Chu, MD, MS Stanford University
  More Information

Publications:
Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT01549652     History of Changes
Other Study ID Numbers: 5HT3 19821, 1R01DA029078
Study First Received: February 13, 2012
Last Updated: March 8, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Narcotics
Substance Withdrawal Syndrome
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Ondansetron
Analgesics, Opioid
Serotonin 5-HT3 Receptor Antagonists
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Psychotropic Drugs
Anti-Anxiety Agents

ClinicalTrials.gov processed this record on July 31, 2014