Trial Outcomes & Findings for Genetic Effects on Dopamine Response to an Opiate (NCT NCT01878006)

NCT ID: NCT01878006

Last Updated: 2021-04-01

Results Overview

Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 15 participants
• Primary outcome timeframe: 90 minutes following injection
• Results posted on: 2021-04-01

Participant Flow

15 subjects were consented for the trial, but 10 subjects were found eligible to start the study.

Participant milestones

Measure	First Morphine, Then Placebo All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline over 20-30 s	First Placebo, Then Morphine All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline over 20-30 s
Study Session 1 STARTED	5	5
Study Session 1 COMPLETED	5	5
Study Session 1 NOT COMPLETED	0	0
Study Session 2 STARTED	5	5
Study Session 2 COMPLETED	5	5
Study Session 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Genetic Effects on Dopamine Response to an Opiate

Baseline characteristics by cohort

Measure	All Study Participants n=10 Participants All participants who started the study.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	10 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants
Race (NIH/OMB) White	7 Participants n=93 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: 90 minutes following injection

Population: The analyses included only those subjects who completed both PET sessions (active and placebo)

Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

Outcome measures

Measure	Morphine n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s	Placebo n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s
11C Raclopride Binding Potential in Caudate	3.25 mCi/ml Standard Deviation 0.4	3.45 mCi/ml Standard Deviation 0.5

PRIMARY outcome

Timeframe: 90 minutes following injection

Population: The analyses included only those subjects who completed both PET sessions (active and placebo)

Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

Outcome measures

Measure	Morphine n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s	Placebo n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s
11C Raclopride Binding Potential in Nucleus Accumbens	2.68 mCi/ml Standard Deviation 0.5	2.84 mCi/ml Standard Deviation 0.4

PRIMARY outcome

Timeframe: 90 minutes following injection

Population: The analyses included only those subjects who completed both PET sessions (active and placebo)

Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

Outcome measures

Measure	Morphine n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s	Placebo n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s
11C Raclopride Binding Potential in Putamen	3.9 mCi/ml Standard Deviation 0.4	4.11 mCi/ml Standard Deviation 0.6

PRIMARY outcome

Timeframe: 90 minutes following injection

Population: The analyses included only those subjects who completed both PET sessions (active and placebo)

Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.

Outcome measures

Measure	Morphine n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s	Placebo n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s
11C Raclopride Binding Potential in Ventral Pallidum	2.68 mCi/ml Standard Deviation 0.4	2.94 mCi/ml Standard Deviation 0.5

SECONDARY outcome

Timeframe: 60 minutes following injection

Population: The analyses included only those subjects who completed both PET sessions (active and placebo)

Area under the curve of the subjective perception-time course - Feel Drug. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve (AUC) for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared. AUC is computed using the trapezoidal rule and has a range of values from 0 to 5500, where 0 reflects no subjective perception at any time point and 5500 reflects maximal subjective perception (score of 100) at all time points after drug administration.

Outcome measures

Measure	Morphine n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s	Placebo n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s
Subjective Perception of Morphine Effect - Feel Drug	3942.8 Units on a scale * min Standard Deviation 856.1	176 Units on a scale * min Standard Deviation 553.1

SECONDARY outcome

Timeframe: 60 minutes following injection

Population: The analyses included only those subjects who completed both PET sessions (active and placebo)

Area under the curve of the subjective perception-time course - Feel High. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve (AUC) for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared. AUC is computed using the trapezoidal rule and has a range of values from 0 to 5500, where 0 reflects no subjective perception at any time point and 5500 reflects maximal subjective perception (score of 100) at all time points after drug administration.

Outcome measures

Measure	Morphine n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s	Placebo n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s
Subjective Perception of Morphine Effect - Feel High	3729.4 Units on a scale * min Standard Deviation 1132.1	175 Units on a scale * min Standard Deviation 553.4

SECONDARY outcome

Timeframe: 60 minutes following injection

Population: The analyses included only those subjects who completed both PET sessions (active and placebo)

Area under the curve of the subjective perception-time course - Like Drug. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve (AUC) for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared. AUC is computed using the trapezoidal rule and has a range of values from 0 to 5500, where 0 reflects no subjective perception at any time point and 5500 reflects maximal subjective perception (score of 100) at all time points after drug administration.

Outcome measures

Measure	Morphine n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s	Placebo n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s
Subjective Perception of Morphine Effect - Like Drug	3078.9 Units on a scale * min Standard Deviation 1881.14	2628.5 Units on a scale * min Standard Deviation 952.1

SECONDARY outcome

Timeframe: 60 minutes following injection

Population: The analyses included only those subjects who completed both PET sessions (active and placebo)

Area under the curve of the subjective perception-time course - Want More. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve (AUC) for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared. AUC is computed using the trapezoidal rule and has a range of values from 0 to 5500, where 0 reflects no subjective perception at any time point and 5500 reflects maximal subjective perception (score of 100) at all time points after drug administration.

Outcome measures

Measure	Morphine n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s	Placebo n=10 Participants All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline (placebo) over 20-30 s
Subjective Perception of Morphine Effect - Want More	1601.1 Units on a scale * min Standard Deviation 1352.4	1277 Units on a scale * min Standard Deviation 1674.6

Adverse Events

Morphine

Serious events: 0 serious events

Other events: 6 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

Measure	Morphine n=10 participants at risk All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline over 20-30 s	Placebo n=10 participants at risk All participants received in counterbalanced order an IV infusion of morphine (10 mg/70 kg) or an equivalent volume of normal saline over 20-30 s
Cardiac disorders Dizziness	40.0% 4/10 • 2 months	0.00% 0/10 • 2 months
Gastrointestinal disorders dyspepsia	10.0% 1/10 • 2 months	0.00% 0/10 • 2 months
Gastrointestinal disorders Nausea	30.0% 3/10 • 2 months	0.00% 0/10 • 2 months
Nervous system disorders Sedation	30.0% 3/10 • 2 months	0.00% 0/10 • 2 months
Nervous system disorders Tremor	10.0% 1/10 • 2 months	0.00% 0/10 • 2 months
Skin and subcutaneous tissue disorders Flushing	40.0% 4/10 • 2 months	0.00% 0/10 • 2 months

Additional Information

Ramchandani, Vijay

National Institute on Alcohol Abuse and Alcoholism

Phone: +1 301 402 8527

Email: vijayr@mail.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place