Clinical trial NCT01549652
Conditions: Opioid Withdrawal Physical Dependence
Sponsor: Stanford University
Start date: 2011-04-01; Completion date: 2016-10-01
Enrollment: 133 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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. 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.

Arms: arm 1: Chronic back pain patients will titrate onto sustained release oral morphine for 30 days, and then will be randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (Naloxone 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants will return to their titrated morphine dose for one week and then return for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants will then taper back to their original dose of morphine for one week. arm 2: Chronic back pain patients will titrate onto sustained release oral morphine for 30 days; during morphine treatment, participants will be randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants will return to the lab to undergo naloxone-induced withdrawal in clinic (Naloxone 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants will then taper back to their original dose of morphine for one week.
Interventions: intervention 1: Ondansetron intervention 2: Placebo intervention 3: Morphine intervention 4: Naloxone 0.4 mg/70 kg intervention 5: Naloxone 0.8 mg/70 kg
Intervention descriptions: intervention 1: Ondansetron 8 mg oral tablet intervention 2: Placebo to Match Ondansetron intervention 3: Sustained release oral morphine, beginning at 30 mg/d, titrated up by 15 mg/d every 2 days until adequate analgesia is achieved intervention 4: Naloxone 0.4 mg/70 kg intravenous intervention 5: Naloxone 0.8 mg/70 kg intravenous

Protocol documents: