5HT3 Antagonists to Treat Opioid Withdrawal and to Prevent the Progression of Physical Dependence
Condition: Opioid Withdrawal; Physical Dependence
MeSH terms: Substance Withdrawal Syndrome
Study type: Interventional

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. 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.
    

Detailed description: 
      This study will be split into two separate investigations, aim 1 and aim 2.

      Study aim 1 (Prevention of Opioid Withdrawal) will investigate whether ondansetron, a
      5HT3-receptor antagonist, can reduce or prevent withdrawal signs and symptoms in patients
      physically dependent on opioids to treat chronic back pain. In this aim, study participants
      will be titrated onto sustained release oral morphine for 30 days after which time they will
      return to the lab to undergo naloxone-induced withdrawal with either 8 mg ondansetron
      pre-treatment (30 min prior to naloxone-induced withdrawal) or placebo. Participants will
      then return to their titrated dose of oral morphine for one week before returning for the
      second study session in which they will receive the opposite pre-treatment (8 mg ondansetron
      or placebo) 30 minutes prior to naloxone-induced withdrawal. Objective opioid withdrawal
      score (OOWS), subjective opioid withdrawal score (SOWS) and Profile of Mood States (POMS)
      will be assessed at baseline and five or seven times during the study sessions at 30 and 37
      days post titration. Beck Depression Inventory, Roland-Morris Questionnaire and State-Trait
      Anxiety Inventory and VAS Pain Score will be assessed at baseline as well as at both study
      sessions (30 and 37 days post titration).

      Study aim 2 (Prevention of Physical Dependence) will investigate whether ondansetron, a 5HT3
      receptor antagonist, can prevent physical dependence in patients taking opioids chronically
      for controlling chronic back pain. Participants will taper onto sustained release oral
      morphine for 10 days then will maintain the effective dose for twenty days (total of 30 days)
      while simultaneously taking 8 mg ondansetron or placebo three times daily with morphine dose.
      After 30 days of morphine plus 8 mg ondansetron or placebo, study participants will return to
      the lab to undergo naloxone-induced withdrawal. OOWS, SOWS, POMS, pain visual analogue scale
      (VAS), Beck Depression Inventory and Roland Morris Disability Index will be administered at
      baseline and at the beginning of each study session (30 days post titration). Furthermore
      OOWS, SOWS and POMS will be administered twice during the first study session and at least
      five times during the second study session (Day 30): at the beginning of the session, after
      IV insertion, and after naloxone-induced opioid withdrawal.
    

Intervention name(s): Ondansetron; Placebo; Morphine; Naloxone 0.4 mg/70 kg; Naloxone 0.8 mg/70 kg
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Ondansetron 8 mg oral tablet; Placebo to Match Ondansetron; Sustained release oral morphine, beginning at 30 mg/d, titrated up by 15 mg/d every 2 days until adequate analgesia is achieved; Naloxone 0.4 mg/70 kg intravenous; Naloxone 0.8 mg/70 kg intravenous
Other intervention name(s): Zofran
Intervention MeSH terms: Morphine; Ondansetron; Naloxone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment