Trial Outcomes & Findings for 5HT3 Antagonists to Treat Opioid Withdrawal and to Prevent the Progression of Physical Dependence (NCT NCT01549652)
NCT ID: NCT01549652
Last Updated: 2019-01-07
Results Overview
Originally developed by Handelsman, the Objective Opioid Withdrawal Scale (OOWS) score is a well-characterized measure of opioid withdrawal in humans, calculated as the sum of a 13-item physician assessment documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. The minimum score of 0 means the patient is not showing any signs of opioid withdrawal. The maximum score of 13 signifies all signs of opioid withdrawal to the largest extent possible. Immediately prior to ondansetron or placebo administration a baseline OOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an OOWS score was taken. If deemed necessary by the clinician, participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an OOWS score was taken. Change from the baseline OOWS score to the score assessed following the last naloxone dose is reported.
COMPLETED
NA
133 participants
Baseline; 15 minutes following last naloxone dose
2019-01-07
Participant Flow
Chronic back pain patients were recruited from the San Francisco Bay Area via recruitment posters, newspaper advertisements, and radio and television announcements.
No enrolled participants were excluded from the study after enrollment and before assignment to groups.
Participant milestones
| Measure |
Prevention of Opioid Withdrawal-Ondansetron
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
Data regarding how many participants received ondansetron first versus placebo first are not accessible.
|
Prevention of Opioid Withdrawal-Placebo
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
Data regarding how many participants received ondansetron first versus placebo first are not accessible.
|
Prevention of Physical Dependence - Ondansetron
Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week.
|
Prevention of Physical Dependence - Placebo
Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
27
|
30
|
40
|
36
|
|
Overall Study
COMPLETED
|
15
|
18
|
23
|
25
|
|
Overall Study
NOT COMPLETED
|
12
|
12
|
17
|
11
|
Reasons for withdrawal
| Measure |
Prevention of Opioid Withdrawal-Ondansetron
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
Data regarding how many participants received ondansetron first versus placebo first are not accessible.
|
Prevention of Opioid Withdrawal-Placebo
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
Data regarding how many participants received ondansetron first versus placebo first are not accessible.
|
Prevention of Physical Dependence - Ondansetron
Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week.
|
Prevention of Physical Dependence - Placebo
Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week.
|
|---|---|---|---|---|
|
Overall Study
Did Not Receive Allocated Intervention
|
0
|
0
|
2
|
0
|
|
Overall Study
Study Drug Titration Failure
|
5
|
6
|
0
|
0
|
|
Overall Study
Withdrawal Effect
|
0
|
2
|
0
|
0
|
|
Overall Study
Did Not Return Due to Withdrawal Effect
|
5
|
1
|
0
|
0
|
|
Overall Study
Problem with Infusion
|
1
|
0
|
0
|
0
|
|
Overall Study
Titration Non-Compliance
|
1
|
3
|
4
|
5
|
|
Overall Study
Titration Side Effects
|
0
|
0
|
6
|
3
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
5
|
3
|
Baseline Characteristics
5HT3 Antagonists to Treat Opioid Withdrawal and to Prevent the Progression of Physical Dependence
Baseline characteristics by cohort
| Measure |
Prevention of Opioid Withdrawal
n=33 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
Data regarding how many participants received ondansetron first versus placebo first are not accessible.
|
Prevention of Physical Dependence-Ondansetron
n=23 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week.
|
Prevention of Physical Dependence-Placebo
n=25 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week.
|
Total
n=81 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
18-65 years
|
33 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
81 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
46 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline; 15 minutes following last naloxone dosePopulation: Participants in the Prevention of Opioid Withdrawal Arm were analyzed.
Originally developed by Handelsman, the Objective Opioid Withdrawal Scale (OOWS) score is a well-characterized measure of opioid withdrawal in humans, calculated as the sum of a 13-item physician assessment documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. The minimum score of 0 means the patient is not showing any signs of opioid withdrawal. The maximum score of 13 signifies all signs of opioid withdrawal to the largest extent possible. Immediately prior to ondansetron or placebo administration a baseline OOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an OOWS score was taken. If deemed necessary by the clinician, participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an OOWS score was taken. Change from the baseline OOWS score to the score assessed following the last naloxone dose is reported.
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=33 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Change in Objective Opioid Withdrawal Score (OOWS) From Baseline (Prevention of Opioid Withdrawal)
Change in OOWS (Ondansetron)
|
3.6 units on a scale
Standard Deviation 2.2
|
|
Change in Objective Opioid Withdrawal Score (OOWS) From Baseline (Prevention of Opioid Withdrawal)
Change in OOWS (Placebo)
|
3.6 units on a scale
Standard Deviation 2.4
|
PRIMARY outcome
Timeframe: Baseline; 15 minutes following last naloxone dosePopulation: Participants in the Prevention of Physical Dependence Arm were analyzed.
Originally developed by Handelsman, the OOWS score is a well-characterized measure of opioid withdrawal in humans, calculated as the sum of a 13-item physician assessment documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. The maximum score is 13 and suggests the patient is showing all signs of opioid withdrawal to the largest extent possible. The minimum score of 0 suggests the patient is not showing any signs of opioid withdrawal. Immediately prior to ondansetron or placebo administration a baseline OOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an OOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an OOWS score was taken. Change from the baseline OOWS score to the score assessed following the last naloxone dose is reported.
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=48 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Change in Objective Opioid Withdrawal Score From Baseline (Prevention of Physical Dependence)
Change in OOWS (Ondansetron)
|
4.5 units on a scale
Standard Deviation 2.5
|
|
Change in Objective Opioid Withdrawal Score From Baseline (Prevention of Physical Dependence)
Change in OOWS (Placebo)
|
4.2 units on a scale
Standard Deviation 2.4
|
SECONDARY outcome
Timeframe: Baseline; 15 minutes following last naloxone dosePopulation: Participants in the Prevention of Opioid Withdrawal Arm were analyzed.
The Subjective Opioid Withdrawal Score (SOWS) score is calculated as the sum of 16 subjective patient-reported symptom scores 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. A maximum score of 64 would suggest the patient is experiencing the symptoms of withdrawal to the maximum extent possible while the lowest score of 0 would suggest the patient is not experiencing any of the symptoms of withdrawal. Immediately prior to ondansetron or placebo administration a baseline SOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an SOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an SOWS score was taken. Change from the baseline SOWS score to the score assessed following the last naloxone dose is reported
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=33 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Change in Subjective Opioid Withdrawal Score (SOWS) From Baseline (Prevention of Opioid Withdrawal)
Change in SOWS (Ondansetron)
|
12.5 units on a scale
Standard Deviation 11.2
|
|
Change in Subjective Opioid Withdrawal Score (SOWS) From Baseline (Prevention of Opioid Withdrawal)
Change in SOWS (Placebo)
|
12.2 units on a scale
Standard Deviation 10.7
|
SECONDARY outcome
Timeframe: 2 study days 1 month apart (at the start of each study visit)Population: Participants in the Prevention of Opioid Withdrawal Arm were analyzed.
The Beck Depression Inventory (a 21-item self-report multiple-choice inventory) yields a single summed score between 0 and 63; higher scores indicate more severe depression. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit).
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=33 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Beck Depression Inventory Score (BDIS) Change From Baseline (Prevention of Opioid Withdrawal)
|
-0.44 units on a scale
Standard Deviation 3.36
|
SECONDARY outcome
Timeframe: Baseline; 15 minutes following last naloxone dosePopulation: Participants in the Prevention of Opioid Withdrawal Arm were analyzed.
Profile of Mood States (POMS) is a 65-question survey of how participants have been feeling over the past week, assessing tension, depression, anger, fatigue, confusion and vigor. Each question is on a 5-point scale: 0 (not at all) to 4 (extremely). Overall score range: 0 to 200 (lower scores corresponding to fewer symptoms), calculated by adding total scores for tension, depression, anger, fatigue and confusing, and subtracting that total score from the total score for vigor. Immediately prior to ondansetron or placebo administration a baseline POMS score was taken. 30 minutes later participants received naloxone, then 15 minutes later a POMS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an POMS score was taken. Change from the baseline POMS score to the score assessed following the last naloxone dose is reported.
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=33 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Profile of Mood States (POMS) Change in Score From Baseline (Prevention of Opioid Withdrawal)
Change in POMS Score (Ondansetron)
|
29.3 units on a scale
Standard Deviation 31.3
|
|
Profile of Mood States (POMS) Change in Score From Baseline (Prevention of Opioid Withdrawal)
Change in POMS Score (Placebo)
|
28.3 units on a scale
Standard Deviation 37.1
|
SECONDARY outcome
Timeframe: 2 study days 1 month apart (at the start of each study visit)Population: Participants in the Prevention of Opioid Withdrawal Arm were analyzed.
The VAS is a 0 to 100 millimeter scale where 0 corresponds to no pain and 100 to extreme pain, used by participants to indicated their level of pain over the last two weeks. Change is from baseline score for average level of pain (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit).
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=33 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Change in Pain Visual Analog Scale (VAS) From Baseline (Prevention of Opioid Withdrawal)
|
-2.68 units on a scale
Standard Deviation 2.23
|
SECONDARY outcome
Timeframe: 2 study days 1 month apart (at the start of each study visit)Population: Participants in the Prevention of Opioid Withdrawal Arm were analyzed.
The Roland-Morris Disability Index is a 24-question instrument used to assess level of disability from lower back pain. Scores range from 0-24 with lower scores corresponding to fewer symptoms. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit).
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=33 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Change in Roland-Morris Disability Index (RMDI) From Baseline (Prevention of Opioid Withdrawal)
|
-2.59 units on a scale
Standard Deviation 4.56
|
SECONDARY outcome
Timeframe: Baseline; 15 minutes following last naloxone dosePopulation: Participants in the Prevention of Physical Dependence Arm were analyzed.
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. A maximum score of 64 would suggest the patient is experiencing the symptoms of withdrawal to the maximum extent possible while the lowest score of 0 would suggest the patient is not experiencing any of the symptoms of withdrawal. Immediately prior to ondansetron or placebo administration a baseline SOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an SOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an SOWS score was taken. Change from the baseline SOWS score to the score assessed following the last naloxone dose is reported
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=48 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Change in Subjective Opioid Withdrawal Score From Baseline (Prevention of Physical Dependence)
Change in SOWS (Ondansetron)
|
16.4 units on a scale
Standard Deviation 13.1
|
|
Change in Subjective Opioid Withdrawal Score From Baseline (Prevention of Physical Dependence)
Change in SOWS (Placebo)
|
12.0 units on a scale
Standard Deviation 10.0
|
SECONDARY outcome
Timeframe: 2 study days 1 month apart (at the start of each study visit)Population: Participants in the Prevention of Physical Dependence Arm were analyzed.
The Beck Depression Inventory (a 21-item self-report multiple-choice inventory) yields a single summed score between 0 and 63; higher scores indicate more severe depression. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit).
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=48 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Beck Depression Inventory Score (BDIS) Change From Baseline (Prevention of Physical Dependence)
Change in BDIS (Ondansetron)
|
-0.6 units on a scale
Standard Deviation 2.6
|
|
Beck Depression Inventory Score (BDIS) Change From Baseline (Prevention of Physical Dependence)
Change in BDIS (Placebo)
|
0.2 units on a scale
Standard Deviation 3.1
|
SECONDARY outcome
Timeframe: Baseline; 15 minutes following last naloxone dosePopulation: Participants in the Prevention of Physical Dependence Arm were analyzed.
(Profile of Mood States) POMS is a 65-question survey of how participants have been feeling over the past week, assessing tension, depression, anger, fatigue, confusion and vigor. Each question is on a 5-point scale: 0 (not at all) to 4 (extremely). Overall score range: 0 to 200 (lower scores corresponding to fewer symptoms), calculated by adding total scores for tension, depression, anger, fatigue and confusing, and subtracting that total score from the total score for vigor. Immediately prior to ondansetron or placebo administration a baseline POMS score was taken. 30 minutes later participants received naloxone, then 15 minutes later a POMS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an POMS score was taken. Change from the baseline POMS score to the score assessed following the last naloxone dose is reported.
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=48 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Profile of Mood States (POMS) Change in Score From Baseline (Prevention of Physical Dependence)
Change in POMS (Ondansetron)
|
36.1 units on a scale
Standard Deviation 27.6
|
|
Profile of Mood States (POMS) Change in Score From Baseline (Prevention of Physical Dependence)
Change in POMS (Placebo)
|
29.2 units on a scale
Standard Deviation 26.3
|
SECONDARY outcome
Timeframe: 2 study days 1 month apart (at the start of each study visit)Population: Participants in the Prevention of Physical Dependence Arm were analyzed.
The VAS is a 0 to 100 millimeter scale where 0 corresponds to no pain and 100 to extreme pain, used by participants to indicated their level of pain over the last two weeks. Change is from baseline score for average level of pain (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit).
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=48 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Change in Pain Visual Analog Scale (VAS) From Baseline (Prevention of Physical Dependence)
Change in VAS Score (Ondansetron)
|
-2.9 units on a scale
Standard Deviation 1.4
|
|
Change in Pain Visual Analog Scale (VAS) From Baseline (Prevention of Physical Dependence)
Change in VAS Score (Placebo)
|
-2.8 units on a scale
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: 2 study days 1 month apart (at the start of each study visit)Population: Participants in the Prevention of Physical Dependence Arm were analyzed.
The Roland-Morris Disability Index is a 24-question instrument used to assess level of disability from lower back pain. Scores range from 0-24 with lower scores corresponding to fewer symptoms. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit).
Outcome measures
| Measure |
Prevention of Opioid Withdrawal
n=48 Participants
Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 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 returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week.
|
|---|---|
|
Change in Roland-Morris Disability (RMDI) Index From Baseline (Prevention of Physical Dependence)
Change in RMDI (Ondansetron)
|
-4.6 units on a scale
Standard Deviation 4.2
|
|
Change in Roland-Morris Disability (RMDI) Index From Baseline (Prevention of Physical Dependence)
Change in RMDI (Placebo)
|
-2.0 units on a scale
Standard Deviation 3.1
|
Adverse Events
Prevention of Opioid Withdrawal
Prevention of Physical Dependence
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. Larry F. Chu
Stanford University School of Medicine Department of Anesthesiology
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place