Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00082030
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2004-04-28
Brief Title:
Function of Catecholamines in the Brain During Depression
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Neural Correlates of Depressive Symptoms and Reward Related Mechanisms Following AMPT Depletion in Remitted Depressed Patients Off Treatment and Healthy Controls
Status:
COMPLETED
Status Verified Date:
2011-11-18
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will explore brain function related to depressive symptoms and will examine DNA for genes that may be involved in depressive disorders particularly genes that regulate synthesis and metabolism of the brain neurotransmitter catecholamine It will compare findings in patients with major depressive disorders who are in remission with those in normal healthy volunteers
Patients with remitted major depressive disorders and healthy normal volunteers between 18 and 60 years of age may be eligible for this study Candidates are screened with a psychiatric and medical history physical examination electrocardiogram and blood and urine tests Participants undergo the following tests and procedures in up to eight visits to the NIH Clinical Center
Memory Tasks and Problem Solving and Brain Imaging
Subjects are tested with measurements of intelligence or memory ability They also undergo magnetic resonance imaging MRI a test that uses a magnetic field and radio waves to produce images of the brain For this procedure the patient lies on a table that is moved into the scanner a narrow cylinder and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process The MRI lasts about 60 minutes
Catecholamine Depletion Study
For this study subjects take capsules containing either AMPT a drug that temporarily reduces brain catecholamine activity or a placebo lactose capsules which do not affect brain catecholamine activity at 9 am 2 pm and 7 pm on one visit and return the next day to take additional capsules at 7 am and noon In addition to the study medication subjects keep a low-monoamine diet eg no chocolate cheese smoked meats and various other foods that will be enumerated and do not smoke drink alcohol or take in food or drink containing caffeine After taking all the study capsules the subjects have positron emission tomography PET and functional MRI fMRI scans as follows
fMRI While lying in the MRI scanner the subject performs a monetary reward task that is somewhat like playing a computer video game for money The amount of cash the subject can win depends on his or her performance It is possible to lose money that was previously won if performance declines This portion of the study provides information on how the brain processes reward and about the role of catecholamines in this process
PET The subject is injected in the arm with a glucose solution that has a radioactive substance attached that can be detected by the PET scanner During the scan the subject looks at photographs of faces on a computer screen and is asked to tell the gender of the persons This test shows brain blood flow and measures brain glucose sugar metabolism which reflects brain activity At the end of the scan subjects are asked about their mood and general well being They return to the Clinical Center the following day for and evaluation of their emotional state
The catecholamine depletion study is repeated a second time 14 days or more after the first Subjects who received AMPT capsules for the first study take lactose capsules for the second study and vice-versa
Patients with remitted major depressive disorders and healthy normal volunteers between 18 and 60 years of age may be eligible for this study Candidates are screened with a psychiatric and medical history physical examination electrocardiogram and blood and urine tests Participants undergo the following tests and procedures in up to eight visits to the NIH Clinical Center
Memory Tasks and Problem Solving and Brain Imaging
Subjects are tested with measurements of intelligence or memory ability They also undergo magnetic resonance imaging MRI a test that uses a magnetic field and radio waves to produce images of the brain For this procedure the patient lies on a table that is moved into the scanner a narrow cylinder and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process The MRI lasts about 60 minutes
Catecholamine Depletion Study
For this study subjects take capsules containing either AMPT a drug that temporarily reduces brain catecholamine activity or a placebo lactose capsules which do not affect brain catecholamine activity at 9 am 2 pm and 7 pm on one visit and return the next day to take additional capsules at 7 am and noon In addition to the study medication subjects keep a low-monoamine diet eg no chocolate cheese smoked meats and various other foods that will be enumerated and do not smoke drink alcohol or take in food or drink containing caffeine After taking all the study capsules the subjects have positron emission tomography PET and functional MRI fMRI scans as follows
fMRI While lying in the MRI scanner the subject performs a monetary reward task that is somewhat like playing a computer video game for money The amount of cash the subject can win depends on his or her performance It is possible to lose money that was previously won if performance declines This portion of the study provides information on how the brain processes reward and about the role of catecholamines in this process
PET The subject is injected in the arm with a glucose solution that has a radioactive substance attached that can be detected by the PET scanner During the scan the subject looks at photographs of faces on a computer screen and is asked to tell the gender of the persons This test shows brain blood flow and measures brain glucose sugar metabolism which reflects brain activity At the end of the scan subjects are asked about their mood and general well being They return to the Clinical Center the following day for and evaluation of their emotional state
The catecholamine depletion study is repeated a second time 14 days or more after the first Subjects who received AMPT capsules for the first study take lactose capsules for the second study and vice-versa
Detailed Description:
The depressive and anhedonic response precipitated by CD raises the possibility that dysfunction of the dopamine system is a stable sometimes latent characteristic of MDD Following this line of reasoning central catecholamine dysfunction as evinced by CD may be equally salient in a subset of unaffected relatives who are at genetic risk for developing the disorder
We plan to extend the phase I project to unaffected relatives of BD and MDD patients in order to evaluate sensitivity to CD as an endophenotype of MDD and BD In order to maximize our statistical power we will be recruiting equal numbers healthy low and high-risk relatives Here risk is defined on the basis of chronological age see below for more detail
Furthermore it has recently become feasible to conduct genome-wide association studies and quantify the burden of risk alleles carried by an individual Certainly the identity of these risk alleles remains unknown or unproven Nevertheless Francis McMahons group with whom we are collaborating have identified upwards of 20 common risk variants in two independent samples Individuals carrying 19 or more of these risk alleles were found to be 4 times more likely to be cases than controls This approach may provide us with another method of quantifying genetic risk
The endophenotypic status of sensitivity to CD will be evaluated with psychometric instruments FDG PET and an fMRI-coupled appetitive learning task We now have access to a high resolution PET scanner High Resolution Research Tomograph that will enable us to study hitherto irresolvable structures of importance such as the habenula and peri-aqueductal gray matter PAG in addition to previously implicated regions such as the ventral striatum and OFC Analysis of the metabolic activity of these regions under sham and CD conditions in both remitted MDD and relatives of BD and MDD patients is of great theoretical import So to is identifying regions of the brain involved in reward response that are selectively impacted by CD a question that we hope to answer through the use of the fMRI-coupled appetitive learning task
We plan to extend the phase I project to unaffected relatives of BD and MDD patients in order to evaluate sensitivity to CD as an endophenotype of MDD and BD In order to maximize our statistical power we will be recruiting equal numbers healthy low and high-risk relatives Here risk is defined on the basis of chronological age see below for more detail
Furthermore it has recently become feasible to conduct genome-wide association studies and quantify the burden of risk alleles carried by an individual Certainly the identity of these risk alleles remains unknown or unproven Nevertheless Francis McMahons group with whom we are collaborating have identified upwards of 20 common risk variants in two independent samples Individuals carrying 19 or more of these risk alleles were found to be 4 times more likely to be cases than controls This approach may provide us with another method of quantifying genetic risk
The endophenotypic status of sensitivity to CD will be evaluated with psychometric instruments FDG PET and an fMRI-coupled appetitive learning task We now have access to a high resolution PET scanner High Resolution Research Tomograph that will enable us to study hitherto irresolvable structures of importance such as the habenula and peri-aqueductal gray matter PAG in addition to previously implicated regions such as the ventral striatum and OFC Analysis of the metabolic activity of these regions under sham and CD conditions in both remitted MDD and relatives of BD and MDD patients is of great theoretical import So to is identifying regions of the brain involved in reward response that are selectively impacted by CD a question that we hope to answer through the use of the fMRI-coupled appetitive learning task
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-M-0160 | None | None | None |