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Genetic Effects on Dopamine Response to an Opiate

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ClinicalTrials.gov Identifier: NCT01878006
Recruitment Status : Completed
First Posted : June 14, 2013
Results First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Alcohol Abuse and Alcoholism (NIAAA) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Other
Conditions Polymorphism-Genetic
Pain
Addiction
Interventions Drug: Morphine
Drug: Placebo
Enrollment 15
Recruitment Details  
Pre-assignment Details 15 subjects were consented for the trial, but 10 subjects were found eligible to start the study.
Arm/Group Title First Morphine, Then Placebo First Placebo, Then Morphine
Hide Arm/Group Description 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 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
Period Title: Study Session 1
Started 5 5
Completed 5 5
Not Completed 0 0
Period Title: Study Session 2
Started 5 5
Completed 5 5
Not Completed 0 0
Arm/Group Title All Study Participants
Hide Arm/Group Description All participants who started the study.
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
<=18 years
0
   0.0%
Between 18 and 65 years
10
 100.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
0
   0.0%
Male
10
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
10
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
  20.0%
White
7
  70.0%
More than one race
1
  10.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title 11C Raclopride Binding Potential in Caudate
Hide Description 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) 33, with cerebellum as the reference region. 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.
Time Frame 90 minutes following injection
Hide Outcome Measure Data
Hide Analysis Population Description
The analyses included only those subjects who completed both PET sessions (active and placebo)
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: mCi/ml
3.25  (0.4) 3.45  (0.5)
2.Primary Outcome
Title 11C Raclopride Binding Potential in Nucleus Accumbens
Hide Description 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) 33, with cerebellum as the reference region. 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.
Time Frame 90 minutes following injection
Hide Outcome Measure Data
Hide Analysis Population Description
The analyses included only those subjects who completed both PET sessions (active and placebo)
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: mCi/ml
2.68  (0.5) 2.84  (0.4)
3.Primary Outcome
Title 11C Raclopride Binding Potential in Putamen
Hide Description 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) 33, with cerebellum as the reference region. 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.
Time Frame 90 minutes following injection
Hide Outcome Measure Data
Hide Analysis Population Description
The analyses included only those subjects who completed both PET sessions (active and placebo)
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: mCi/ml
3.9  (0.4) 4.11  (0.6)
4.Primary Outcome
Title 11C Raclopride Binding Potential in Ventral Pallidum
Hide Description 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) 33, with cerebellum as the reference region. 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.
Time Frame 90 minutes following injection
Hide Outcome Measure Data
Hide Analysis Population Description
The analyses included only those subjects who completed both PET sessions (active and placebo)
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: mCi/ml
2.68  (0.4) 2.94  (0.5)
5.Secondary Outcome
Title Subjective Perception of Morphine Effect - Feel Drug
Hide Description 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 for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.
Time Frame 60 minutes following injection
Hide Outcome Measure Data
Hide Analysis Population Description
The analyses included only those subjects who completed both PET sessions (active and placebo)
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale * min
3942.8  (856.1) 176  (553.1)
6.Secondary Outcome
Title Subjective Perception of Morphine Effect - Feel High
Hide Description 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 for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.
Time Frame 60 minutes following injection
Hide Outcome Measure Data
Hide Analysis Population Description
The analyses included only those subjects who completed both PET sessions (active and placebo)
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale * min
3729.4  (1132.1) 175  (553.4)
7.Secondary Outcome
Title Subjective Perception of Morphine Effect - Like Drug
Hide Description 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 for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.
Time Frame 60 minutes following injection
Hide Outcome Measure Data
Hide Analysis Population Description
The analyses included only those subjects who completed both PET sessions (active and placebo)
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale * min
3078.9  (1881.14) 2628.5  (952.1)
8.Secondary Outcome
Title Subjective Perception of Morphine Effect - Want More
Hide Description 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 for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.
Time Frame 60 minutes following injection
Hide Outcome Measure Data
Hide Analysis Population Description
The analyses included only those subjects who completed both PET sessions (active and placebo)
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale * min
1601.1  (1352.4) 1277  (1674.6)
Time Frame 2 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Morphine Placebo
Hide Arm/Group Description 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 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
All-Cause Mortality
Morphine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Morphine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Morphine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   6/10 (60.00%)   0/10 (0.00%) 
Cardiac disorders     
Dizziness   4/10 (40.00%)  0/10 (0.00%) 
Gastrointestinal disorders     
dyspepsia   1/10 (10.00%)  0/10 (0.00%) 
Nausea   3/10 (30.00%)  0/10 (0.00%) 
Nervous system disorders     
Sedation   3/10 (30.00%)  0/10 (0.00%) 
Tremor   1/10 (10.00%)  0/10 (0.00%) 
Skin and subcutaneous tissue disorders     
Flushing   4/10 (40.00%)  0/10 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Ramchandani, Vijay
Organization: National Institute on Alcohol Abuse and Alcoholism
Phone: +1 301 402 8527
EMail: vijayr@mail.nih.gov
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute on Alcohol Abuse and Alcoholism (NIAAA) )
ClinicalTrials.gov Identifier: NCT01878006     History of Changes
Other Study ID Numbers: 130061
13-AA-0061
First Submitted: June 12, 2013
First Posted: June 14, 2013
Results First Submitted: August 10, 2018
Results First Posted: October 23, 2018
Last Update Posted: October 23, 2018