Drug AbuseNCT00951314
Brain Glutamate Receptors and Cocaine Dependence
An observational study of Drug Abuse and Cocaine Dependence, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial summary
Objective: Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. Read more about this study
- Who is it for?
- Ages 20 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Abuse, Cocaine Dependence
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jul 2009to 19 Mar 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Cocaine dependent participants must meet DSM-IV criteria for cocaine dependence at the time of participation.
- Control participants who provide appropriate matches for cocaine-dependent participants will be recruited on the following characteristics: age, and when possible, parental socio-economic status and/or years of parental education.
Who cannot join
- Control Participants:
- Psychiatric disease: DSM-IV criteria will be used (American Psychiatric Association, 1994). No subject with a current axis I diagnosis (except for nicotine dependence) will be allowed. Claustrophobia is also exclusionary.
- History of Drug Abuse: Volunteers reporting current or having a significant history of illicit drug abuse will be excluded from the study. Subjects may use moderate amounts of alcohol and caffeine and smoke an occasional marijuana cigarette, but must not be dependent on alcohol, caffeine or marijuana. No alcohol or marijuana for at least 24 hours prior to scanning. No smoking after midnight on the night before a scan.
- Current or Past Medication Use: Volunteers may not currently use chronic (daily for more than 10 to 14 days in the last month) prescription or over the counter medications, (including, but not limited to, anti-hypertensive, anti-allergy, pain). Over the counter or prescription medications may be used on an occasional basis (for treatment of self-limited conditions, such as occasional headache, musculoskeletal discomfort, allergic symptoms or pain). All medications will be discontinued at least 5 days before the experimental session.
- CNS disease: History of known structural brain abnormalities (e.g., neoplasm, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), history of head trauma (defined as documented loss of consciousness > 5 min), history of seizures as an adult, sleep apnea, tic disorder.
- Cardiovascular, pulmonary, or systemic disease: Repeated (measured on three separate occasions) diastolic blood pressure >90 mm Hg, or systolic blood pressure >135 mm Hg, known arrhythmia, symptomatic or known coronary artery disease; history of endocarditis, cerebral embolism, obstructive pulmonary disease, Factive tuberculosis, known endocrine disease (derangements in adrenal, thyroid, bone or reproductive function), known chronic renal or hepatic dysfunction, HIV seropositive, known current autoimmune disease involving the CNS.
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- Miscellaneous exclusionary criteria: Body weight greater than 300 lbs. Hematocrit < 39.0 for males or < 36.0 for females. Participants are also excluded if veins are inaccessible.
- Radiation exposure: Any subject who has participated in any research studies in which he/she received a radiation exposure that would result in combination with the present study, in a total effective radiation exposure (from research studies) exceeding 5.0 rem in a year.
- Novocain allergy or lack of bilateral ulner and radial arterial patency in subjects receiving arterial catheter as assessed by an Allen s test or Dopler test artery patency for all subjects to be catheterized.
- Presence in body of metallic implants or materials that could be moved by the magnet of the MRI scanner: pacemakers, surgical implants, aneurism clips, dental braces, bullet(s) or other metallic materials. A history of working with metal with consequent possible metal fragments in the body.
- Inability to lie flat for a few hours for the PET scans
- Women who are pregnant or lactating and children under the age of 18 will be excluded to avoid unnecessary exposure to radiation to these populations.
- Cocaine Dependent Subjects:
- In addition to the exclusion criteria listed above with the exception of item i. b), subjects in this group will be excluded if:
- They are actively seeking or engaged in substance abuse treatment. Justification: Videos viewed during this study may produce drug craving, producing a significant risk of relapse in a dependent individual attempting to remain abstinent. Any participant seeking treatment will be referred to treatment, since delaying entry into treatment to participate in a study unnecessarily increases exposure to the risks associated with active cocaine dependence. Assessment tool(s): Clinical interview at screening and repeat questioning at time of consent.
- They are dependent on other substances except nicotine or cocaine at the time of participation. Use of other abused substances will be allowed as long as they are not currently dependent on any drug except nicotine and cocaine. Justification: Dependence on other substances may result in unique CNS deficits that would increase the noise in our data. Further, other dependence may contaminate neural processes examined. Nicotine dependence will be allowed since nicotine use is not associated with a drug high in normal usage and the prevalence of nicotine dependence in cocaine using individuals may make it impractical to exclude them. Assessment tool(s): Substance Use Disorders module of the SCID with confirmation by clinical interview and negative urine drug screen. Positive screens for cocaine are allowed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute on Drug Abuse, Biomedical Research Center (BRC)
Baltimore, Maryland, 21224
About this study
Official title: Cocaine Dependence, Metabotropic Glutamate Receptor Subtype 5 (mGluR5) Density, Genetics and Craving
Objective:
Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. Cocaine addiction may be mediated by neuroadaptations in reward-related learning and memory processes in the mesocorticolimbic dopamine system and glutamatergic corticolimbic circuitry. Metabotropic glutamate subtype 5 receptors (mGluR5) likely play essential roles in mediating some of the actions of drugs of abuse. Animal studies have shown that mGluR5 knock-out or blockade reduces self-administration of cocaine and cocaine-induced hyper-locomotion. However, to what extent mGluR5 are involved in the pathophysiology of cocaine addiction in humans is currently unknown, partly due to the lack of suitable methods to reliably quantify mGluR5 in the living human brain.
Read more
This protocol aims to determine whether the density of mGluR5 in brain is altered in participants with cocaine addiction compared to healthy controls using positron emission tomography (PET) and the recently developed radiotracer for mGluR5, [18F]SP203. We also aim to determine whether this density is related to genotype, history of cocaine use, and/or craving for cocaine.
Study Population:
The study populations will consist of healthy adults with no history of substance abuse and a matched group of healthy current primary cocaine dependent male and female participants (20-50 years old.; N=40/group).
Design:
Density of mGluR5 will be measured in cocaine dependent participants and healthy adults volunteers with PET and (18F)SP203, a radioligand with specificity for mGluR5. All participants will undergo genotyping to identify normal or variant mGluR5 gene associated with drug abuse. The intensity of craving for cocaine will be assessed while watching a video about cocaine use.
Outcome measures:
Density of mGluR5 will be compared between cocaine dependent participants and healthy controls. In addition, correlation among the genetic polymorphism, the craving response, and the density of mGluR5 will be determined.
Read the detailed description
Objective:
Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. Cocaine addiction may be mediated by neuroadaptations in reward-related learning and memory processes in the mesocorticolimbic dopamine system and glutamatergic corticolimbic circuitry. Metabotropic glutamate subtype 5 receptors (mGluR5) likely play essential roles in mediating some of the actions of drugs of abuse. Animal studies have shown that mGluR5 knock-out or blockade reduces self-administration of cocaine and cocaine-induced hyper-locomotion. However, to what extent mGluR5 are involved in the pathophysiology of cocaine addiction in humans is currently unknown, partly due to the lack of suitable methods to reliably quantify mGluR5 in the living human brain.
This protocol aims to determine whether the density of mGluR5 in brain is altered in participants with cocaine addiction compared to healthy controls using positron emission tomography (PET) and the recently developed radiotracer for mGluR5, [18F]SP203. We also aim to determine whether this density is related to genotype, history of cocaine use, and/or craving for cocaine.
Study Population:
The study populations will consist of healthy adults with no history of substance abuse and a matched group of healthy current primary cocaine dependent male and female participants (20-55 years old.; N=40/group).
Design:
Density of mGluR5 will be measured in cocaine dependent participants and healthy adults volunteers with PET and (18(F)SP203, a radioligand with specificity for mGluR5. All participants will undergo genotyping to identify normal or variant mGluR5 gene associated with drug abuse. The intensity of craving for cocaine will be assessed while watching a video about cocaine use.
Outcome measures:
Density of mGluR5 will be compared between cocaine dependent participants and healthy controls. In addition, correlation among the genetic polymorphism, the craving response, and the density of mGluR5 will be determined.
- Conditions
- Drug Abuse, Cocaine Dependence
- Keywords
- Genetic Polymorphisms, Metabotropic Glutamate Receptors, Positron Emission Tomograhy (PET), Cocaine Dependence, Cue-Induced Craving, Drug Abuse
- Medical subject headings
- Substance-Related Disorders, Cocaine-Related Disorders
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine if cocaine dependent participants have a different mGluR5 density than healthy controls
Secondary outcomes (1)
Determine if mGluR5 density in ventral striatum in cocaine dependent participants is associated with craving.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2009 (estimated)
- Study start14 Jul 2009
- Study completion19 Mar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Drug AbuseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Investigators
- Alane Kimes, Ph.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00951314
- Sponsor's protocol ID
- 090188
- Other IDs
- 09-DA-0188
- Status last verified
- 19 Mar 2013
- First submitted
- 1 Aug 2009
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Ametamey SM, Kessler LJ, Honer M, Wyss MT, Buck A, Hintermann S, Auberson YP, Gasparini F, Schubiger PA. Radiosynthesis and preclinical evaluation of 11C-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5. J Nucl Med. 2006 Apr;47(4):698-705.
PubMed 16595505Ametamey SM, Treyer V, Streffer J, Wyss MT, Schmidt M, Blagoev M, Hintermann S, Auberson Y, Gasparini F, Fischer UC, Buck A. Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688. J Nucl Med. 2007 Feb;48(2):247-52.
PubMed 17268022Backstrom P, Hyytia P. Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking. Neuropsychopharmacology. 2006 Apr;31(4):778-86. doi: 10.1038/sj.npp.1300845.
PubMed 16123768
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cocaine Dependence, Metabotropic Glutamate Receptor Subtype 5 (mGluR5) Density, Genetics and Craving
- ClinicalTrials.gov ID
- NCT00951314
- Acronym / sponsor ID
- 090188
- Conditions
- Drug Abuse, Cocaine Dependence
- Keywords
- Genetic Polymorphisms, Metabotropic Glutamate Receptors, Positron Emission Tomograhy (PET), Cocaine Dependence, Cue-Induced Craving, Drug Abuse
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 14 Jul 2009
- Study completion
- 19 Mar 2013
- First posted
- 4 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objective:
Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. Cocaine addiction may be mediated by neuroadaptations in reward-related learning and memory processes in the mesocorticolimbic dopamine system and glutamatergic corticolimbic circuitry. Metabotropic glutamate subtype 5 receptors (mGluR5) likely play essential roles in mediating some of the actions of drugs of abuse. Animal studies have shown that mGluR5 knock-out or blockade reduces self-administration of cocaine and cocaine-induced hyper-locomotion. However, to what extent mGluR5 are involved in the pathophysiology of cocaine addiction in humans is currently unknown, partly due to the lack of suitable methods to reliably quantify mGluR5 in the living human brain.
This protocol aims to determine whether the density of mGluR5 in brain is altered in participants with cocaine addiction compared to healthy controls using positron emission tomography (PET) and the recently developed radiotracer for mGluR5, [18F]SP203. We also aim to determine whether this density is related to genotype, history of cocaine use, and/or craving for cocaine.
Study Population:
The study populations will consist of healthy adults with no history of substance abuse and a matched group of healthy current primary cocaine dependent male and female participants (20-50 years old.; N=40/group).
Design:
Density of mGluR5 will be measured in cocaine dependent participants and healthy adults volunteers with PET and (18F)SP203, a radioligand with specificity for mGluR5. All participants will undergo genotyping to identify normal or variant mGluR5 gene associated with drug abuse. The intensity of craving for cocaine will be assessed while watching a video about cocaine use.
Outcome measures:
Density of mGluR5 will be compared between cocaine dependent participants and healthy controls. In addition, correlation among the genetic polymorphism, the craving response, and the density of mGluR5 will be determined.
Detailed description
Objective:
Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. Cocaine addiction may be mediated by neuroadaptations in reward-related learning and memory processes in the mesocorticolimbic dopamine system and glutamatergic corticolimbic circuitry. Metabotropic glutamate subtype 5 receptors (mGluR5) likely play essential roles in mediating some of the actions of drugs of abuse. Animal studies have shown that mGluR5 knock-out or blockade reduces self-administration of cocaine and cocaine-induced hyper-locomotion. However, to what extent mGluR5 are involved in the pathophysiology of cocaine addiction in humans is currently unknown, partly due to the lack of suitable methods to reliably quantify mGluR5 in the living human brain.
This protocol aims to determine whether the density of mGluR5 in brain is altered in participants with cocaine addiction compared to healthy controls using positron emission tomography (PET) and the recently developed radiotracer for mGluR5, [18F]SP203. We also aim to determine whether this density is related to genotype, history of cocaine use, and/or craving for cocaine.
Study Population:
The study populations will consist of healthy adults with no history of substance abuse and a matched group of healthy current primary cocaine dependent male and female participants (20-55 years old.; N=40/group).
Design:
Density of mGluR5 will be measured in cocaine dependent participants and healthy adults volunteers with PET and (18(F)SP203, a radioligand with specificity for mGluR5. All participants will undergo genotyping to identify normal or variant mGluR5 gene associated with drug abuse. The intensity of craving for cocaine will be assessed while watching a video about cocaine use.
Outcome measures:
Density of mGluR5 will be compared between cocaine dependent participants and healthy controls. In addition, correlation among the genetic polymorphism, the craving response, and the density of mGluR5 will be determined.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 20 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Cocaine dependent participants must meet DSM-IV criteria for cocaine dependence at the time of participation.
- Control participants who provide appropriate matches for cocaine-dependent participants will be recruited on the following characteristics: age, and when possible, parental socio-economic status and/or years of parental education.
Key exclusion criteria (16 listed)
- Psychiatric disease: DSM-IV criteria will be used (American Psychiatric Association, 1994). No subject with a current axis I diagnosis (except for nicotine dependence) will be allowed. Claustrophobia is also exclusionary.
- History of Drug Abuse: Volunteers reporting current or having a significant history of illicit drug abuse will be excluded from the study. Subjects may use moderate amounts of alcohol and caffeine and smoke an occasional marijuana cigarette, but must not be dependent on alcohol, caffeine or marijuana. No alcohol or marijuana for at least 24 hours prior to scanning. No smoking after midnight on the night before a scan.
- Current or Past Medication Use: Volunteers may not currently use chronic (daily for more than 10 to 14 days in the last month) prescription or over the counter medications, (including, but not limited to, anti-hypertensive, anti-allergy, pain). Over the counter or prescription medications may be used on an occasional basis (for treatment of self-limited conditions, such as occasional headache, musculoskeletal discomfort, allergic symptoms or pain). All medications will be discontinued at least 5 days before the experimental session.
- CNS disease: History of known structural brain abnormalities (e.g., neoplasm, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), history of head trauma (defined as documented loss of consciousness > 5 min), history of seizures as an adult, sleep apnea, tic disorder.
- Cardiovascular, pulmonary, or systemic disease: Repeated (measured on three separate occasions) diastolic blood pressure >90 mm Hg, or systolic blood pressure >135 mm Hg, known arrhythmia, symptomatic or known coronary artery disease; history of endocarditis, cerebral embolism, obstructive pulmonary disease, Factive tuberculosis, known endocrine disease (derangements in adrenal, thyroid, bone or reproductive function), known chronic renal or hepatic dysfunction, HIV seropositive, known current autoimmune disease involving the CNS.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Determine if cocaine dependent participants have a different mGluR5 density than healthy controls
1 secondary outcome
Determine if mGluR5 density in ventral striatum in cocaine dependent participants is associated with craving.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 16595505Ametamey SM, Kessler LJ, Honer M, Wyss MT, Buck A, Hintermann S, Auberson YP, Gasparini F, Schubiger PA. Radiosynthesis and preclinical evaluation of 11C-ABP688 as a probe for imaging the metabotropic glutamate receptor subtype 5. J Nucl Med. 2006 Apr;47(4):698-705.
- Background: PubMed 17268022Ametamey SM, Treyer V, Streffer J, Wyss MT, Schmidt M, Blagoev M, Hintermann S, Auberson Y, Gasparini F, Fischer UC, Buck A. Human PET studies of metabotropic glutamate receptor subtype 5 with 11C-ABP688. J Nucl Med. 2007 Feb;48(2):247-52.
- Background: PubMed 16123768Backstrom P, Hyytia P. Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking. Neuropsychopharmacology. 2006 Apr;31(4):778-86. doi: 10.1038/sj.npp.1300845.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alane Kimes, Ph.D. principal investigator
National Institute on Drug Abuse (NIDA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Drug Abuse and Cocaine Dependence, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine if cocaine dependent participants have a different mGluR5 density than healthy controls. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00951314, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018; AzTrials last refreshed its copy on 7 Nov 2026.