Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00369798
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2006-08-25
Brief Title:
Antidepressant Effects on cAMP Specific Phosphodiesterase PDE4 in Depressed Patients
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Antidepressant Effects on cAMP Specific Phosphodiesterase PDE 4 in Depressed Patients
Status:
COMPLETED
Status Verified Date:
2016-10-12
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:
The primary purpose of this protocol is to compare PDE4 levels before and after starting a selective serotonin reuptake inhibitor SSRI sertraline citalopram or escitalopram in unmedicated depressed patients The secondary purpose is to compare PDE4 levels between unmedicated depressed patients and healthy subjects
Detailed Description:
Although direct pharmacological effects of antidepressant should manifest rapidly before significant symptom relief appears typically antidepressant treatment needs to be continued for 2 to 4 weeks This delayed onset of clinical effects indicates involvement of adaptive changes in antidepressant effects Rodent studies have consistently shown upregulation of the 3 5-cyclic adenosine monophosphate cAMP system induced by different types of chronic but not acute antidepressant treatment including serotonin and norepinephrine uptake inhibitors monoamine oxidase inhibitors tricyclic antidepressants lithium and electroconvulsions cAMP is synthesized from adenosine 5-triphosphate ATP by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases PDEs Type 4 PDE PDE4 is selective to cAMP in the brain Among components of the cAMP pathway PDE4 appears to be critical for antidepressant effects because an inhibitor of PDE4 4-3-cyclopenotoxyl-4-methoxyphenyl-2-pyrrolidone rolipram showed antidepressant effects both in animals and humans and various forms of antidepressant treatment induced increase in PDE4 in rodents However without imaging the cAMP pathway before and after antidepressant treatment in depressives it is not possible to study adaptive changes in the signal transduction system and its role in the symptom relief
Recently R-11Crolipram has been successfully used to image PDE4 in animals and humans We have confirmed that PDE4 levels can be measured reliably by performing R-11Crolipram positron emission tomography PET with multiple arterial sampling even in rats The primary purpose of this protocol is to compare PDE4 levels before and after starting a selective serotonin reuptake inhibitor SSRI sertraline citalopram or escitalopram in unmedicated depressed patients The secondary purpose is to compare PDE4 levels between unmedicated depressed patients and healthy subjects Baseline scans of patients will be used for this second comparison For the first time these comparisons have become possible with the new PET agent R-11Crolipram The findings will advance understanding on the role of cAMP signal transduction system in the pathology of depression and the mechanisms of antidepressant effects
Recently R-11Crolipram has been successfully used to image PDE4 in animals and humans We have confirmed that PDE4 levels can be measured reliably by performing R-11Crolipram positron emission tomography PET with multiple arterial sampling even in rats The primary purpose of this protocol is to compare PDE4 levels before and after starting a selective serotonin reuptake inhibitor SSRI sertraline citalopram or escitalopram in unmedicated depressed patients The secondary purpose is to compare PDE4 levels between unmedicated depressed patients and healthy subjects Baseline scans of patients will be used for this second comparison For the first time these comparisons have become possible with the new PET agent R-11Crolipram The findings will advance understanding on the role of cAMP signal transduction system in the pathology of depression and the mechanisms of antidepressant effects
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 |
|---|---|---|---|
| 06-M-0215 | None | None | None |