Trial Outcomes & Findings for Functional Magnetic Resonance Imaging of Opioid Withdrawal in Healthy Human Volunteers (NCT NCT01006707)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

15 participants

Primary outcome timeframe

36 minutes

Results posted on

2017-11-17

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Run-in Participants received pretreatment with placebo to match ondansetron in Study Session 1 prior to randomization to cross-over treatment arms in Study Sessions 2 and 3.	Ondansetron, Then Placebo Participants received pretreatment with ondansetron (8mg IV Bolus) in Study Session 2 then placebo to match ondansetron in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.	Placebo, Then Ondansetron Participants received pretreatment with placebo to match ondansetron in Study Session 2 then ondansetron (8mg IV Bolus) in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.
Study Session 1 STARTED	15	0	0
Study Session 1 COMPLETED	10	0	0
Study Session 1 NOT COMPLETED	5	0	0
Study Session 2 STARTED	0	4	6
Study Session 2 COMPLETED	0	4	6
Study Session 2 NOT COMPLETED	0	0	0
Study Session 3 STARTED	0	4	6
Study Session 3 COMPLETED	0	4	6
Study Session 3 NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Run-in Participants received pretreatment with placebo to match ondansetron in Study Session 1 prior to randomization to cross-over treatment arms in Study Sessions 2 and 3.	Ondansetron, Then Placebo Participants received pretreatment with ondansetron (8mg IV Bolus) in Study Session 2 then placebo to match ondansetron in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.	Placebo, Then Ondansetron Participants received pretreatment with placebo to match ondansetron in Study Session 2 then ondansetron (8mg IV Bolus) in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.
Study Session 1 Lost to Follow-up	2	0	0
Study Session 1 Could not tolerate withdrawal in scanner	3	0	0

Baseline Characteristics

Functional Magnetic Resonance Imaging of Opioid Withdrawal in Healthy Human Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=10 Participants All participants received placebo during Study Session 1 (placebo run-in), then were randomized to receive pretreatment with ondansetron (8mg IV Bolus) in Study Session 2 then placebo to match ondansetron in Study Session 3, or pretreatment with placebo to match ondansetron in Study Session 2 then ondansetron (8mg IV Bolus) in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.
Age, Continuous	27.1 years STANDARD_DEVIATION 4.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants
Weight	74.33 kilograms STANDARD_DEVIATION 4.4 • n=5 Participants
Height	177.9 centimeters STANDARD_DEVIATION 4.8 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Ondansetron n=10 Participants All participants received pretreatment with ondansetron (8mg IV Bolus) and with placebo to match ondansetron. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.	Placebo Participants received pretreatment with placebo to match ondansetron in Study Session 2 then ondansetron (8mg IV Bolus) in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.
Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration Left inferior frontal gyrus, orbital (OOWS)	0.519 correlation coefficient	—
Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration Right inferior frontal gyrus, orbital (OOWS)	0.562 correlation coefficient	—
Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration Right superior frontal gyrus, medial (SOWS)	0.478 correlation coefficient	—
Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration Right inferior frontal gyrus, orbital (SOWS)	0.486 correlation coefficient	—
Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration Left superior temporal gyrus (OOWS)	-0.612 correlation coefficient	—
Brain Regions With Increases or Decreases in Amplitude of Low Frequency Fluctuations (ALFF) Associated With Ondansetron Administration Left caudate head (SOWS)	0.475 correlation coefficient	—

SECONDARY outcome

Timeframe: 5 Minutes Following Ondansetron or Placebo Administration

Population: Participants completing the protocol were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	All Ondansetron n=10 Participants All participants received pretreatment with ondansetron (8mg IV Bolus) and with placebo to match ondansetron. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.	Placebo n=10 Participants Participants received pretreatment with placebo to match ondansetron in Study Session 2 then ondansetron (8mg IV Bolus) in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.
Objective Opioid Withdrawal Scale Score 5 Minutes Following Ondansetron or Placebo Administration	1 units on a scale Standard Deviation 0.5	2 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: 15 Minutes Following Ondansetron or Placebo Administration

Population: Participants completing the protocol were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	All Ondansetron n=10 Participants All participants received pretreatment with ondansetron (8mg IV Bolus) and with placebo to match ondansetron. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.	Placebo n=10 Participants Participants received pretreatment with placebo to match ondansetron in Study Session 2 then ondansetron (8mg IV Bolus) in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.
Objective Opioid Withdrawal Scale Score 15 Minutes Following Ondansetron or Placebo Administration	2.7 units on a scale Standard Deviation 1.1	2.2 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: 20 minutes following Ondansetron or Placebo administration

Population: Participants completing the protocol were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	All Ondansetron n=10 Participants All participants received pretreatment with ondansetron (8mg IV Bolus) and with placebo to match ondansetron. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.	Placebo n=10 Participants Participants received pretreatment with placebo to match ondansetron in Study Session 2 then ondansetron (8mg IV Bolus) in Study Session 3. Bolus was be given at the start of the study for 30 minutes by the unblinded investigator.
Subjective Opioid Withdrawal Scale (SOWS) Score 20 Minutes Following Ondansetron or Placebo Administration	5.7 units on a scale Standard Deviation 4.5	8.1 units on a scale Standard Deviation 7.2

Adverse Events

Ondansetron

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Larry Chu

Stanford University School of Medicine

Phone: (650) 723-6632

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place