Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00026585
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2001-11-10
Brief Title:
Examination of Tamoxifen in Acute Mania in Patients With Bipolar I Disorder
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Double-Blind Study Examining the Efficacy of the Protein Kinase C Inhibitor Tamoxifen in the Treatment of Acute Mania
Status:
COMPLETED
Status Verified Date:
2008-05-20
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 purpose of this study is to examine how the drug tamoxifen affects the brain in patients with bipolar I disorder
Bipolar Disorder BD is a severe chronic and often life-threatening illness for which safe and effective treatments are necessary The mood stabilizing effects of lithium and valproate have revolutionized the treatment of patients with BD However a significant percentage of patients do not respond fully to these drugs and the biochemical basis for the antimanic and mood-stabilizing actions of lithium and valproate is unclear Both drugs inhibit protein kinase C PKC There is a need to investigate the efficacy of a direct PKC inhibitor in the treatment of acute mania Tamoxifen is currently the only relatively selective PKC inhibitor available for human use
Participants in this study will be screened with a physical psychiatric and eye examination and blood and urine tests Eligible participants will be hospitalized at the Clinical Center for at least 4 weeks They will be tapered off all psychiatric medication and kept drug free for 2 to 7 days They will also be put on a low-monoamine low-caffeine diet Participants will be randomly assigned to receive either tamoxifen or placebo an inactive pill for 3 weeks During this time participants will have daily pulse and blood pressure measurements several electrocardiograms EKGs and blood draws Weight measurements will be taken at least twice during the study and caffeine or dextromethorphan will be given at the beginning and end of the study to test how tamoxifen affects the way the body eliminates other medications Participants will have a physical examination at the end of the study
At the end of this 4-week study some participants may continue the study and will receive tamoxifen for an additional 3 weeks At the conclusion of the study participants psychiatric status will be reassessed and long-term psychiatric treatment for their mood disorders will be arranged
Bipolar Disorder BD is a severe chronic and often life-threatening illness for which safe and effective treatments are necessary The mood stabilizing effects of lithium and valproate have revolutionized the treatment of patients with BD However a significant percentage of patients do not respond fully to these drugs and the biochemical basis for the antimanic and mood-stabilizing actions of lithium and valproate is unclear Both drugs inhibit protein kinase C PKC There is a need to investigate the efficacy of a direct PKC inhibitor in the treatment of acute mania Tamoxifen is currently the only relatively selective PKC inhibitor available for human use
Participants in this study will be screened with a physical psychiatric and eye examination and blood and urine tests Eligible participants will be hospitalized at the Clinical Center for at least 4 weeks They will be tapered off all psychiatric medication and kept drug free for 2 to 7 days They will also be put on a low-monoamine low-caffeine diet Participants will be randomly assigned to receive either tamoxifen or placebo an inactive pill for 3 weeks During this time participants will have daily pulse and blood pressure measurements several electrocardiograms EKGs and blood draws Weight measurements will be taken at least twice during the study and caffeine or dextromethorphan will be given at the beginning and end of the study to test how tamoxifen affects the way the body eliminates other medications Participants will have a physical examination at the end of the study
At the end of this 4-week study some participants may continue the study and will receive tamoxifen for an additional 3 weeks At the conclusion of the study participants psychiatric status will be reassessed and long-term psychiatric treatment for their mood disorders will be arranged
Detailed Description:
Bipolar Disorder BD is a common severe chronic and often life-threatening illness Suicide is the cause of death in 10-20 of individuals with BD The discovery of lithiums efficacy as a mood-stabilizing agent has since revolutionized the treatment of patients with BD However approximately 50 of patients do not respond fully to lithium and the biochemical basis for lithiums antimanic and mood-stabilizing actions remains to be fully elucidated Elucidation of the mechanisms by which lithium stabilizes an underlying dysregulation of limbic and limbic-associated function also offers the potential to delineate the underlying pathophysiology of BD however a major problem inherent in neuropharmacologic research is the difficulty in attributing therapeutic relevance to any observed biochemical finding One powerful approach is to identify common biochemical targets which are modified by drugs belonging to the same therapeutic class eg mood-stabilizing agents but possessing distinct chemical structures when administered in a therapeutically relevant paradigm ie effects which are observed upon chronic drug administration and yet persist beyond abrupt drug discontinuation In this context it is noteworthy that both valproic acid VPA and lithium with different chemical structures belong to the same therapeutic class and cause considerable inhibition of protein kinase C PKC The PKC signaling pathway is clearly a target for the actions of two structurally highly dissimilar antimanic agents -- lithium and VPA Do these effects of lithium and VPA on PKC signaling have any clinical relevance There is thus a clear need to investigate the potential efficacy of a direct PKC inhibitor in the treatment of acute mania There is currently only one relatively selective PKC inhibitor available for human use- Tamoxifen Tamoxifen TAM a synthetic nonsteroidal antiestrogen has been widely used in the treatment of breast cancer TAMs potent inhibitory effects on PKC are striking Recently our group conducted the first open-label study with TAM in acute mania In this study TAM resulted in a significant decrease in manic symptoms within a short period of time 3-7 days
The overarching goal of this proposal is to test the hypothesis that PKC inhibition is part of the mechanism of the therapeutic effect of mood stabilizing drugs The proposal derives from and builds on our published open-label study of TAM in acute mania Bebchuk et al 2000 However the efficacy of TAM monotherapy in acute mania has only been reported in an open-label study and has not yet been evaluated in a randomized double blind placebo-controlled study
Male or female patients ages 18 to 65 with a diagnosis of bipolar I disorder manic or mixed with or without psychotic features will be randomized to double-blind treatment to receive either TAM 20-140 mgday or placebo for a period of 3 weeks Following this acute period the patients will receive either open-label TAM or treatment as clinically indicated Approximately 50 patients with acute mania will be enrolled in the study Biochemical measures will be obtained during the study
The overarching goal of this proposal is to test the hypothesis that PKC inhibition is part of the mechanism of the therapeutic effect of mood stabilizing drugs The proposal derives from and builds on our published open-label study of TAM in acute mania Bebchuk et al 2000 However the efficacy of TAM monotherapy in acute mania has only been reported in an open-label study and has not yet been evaluated in a randomized double blind placebo-controlled study
Male or female patients ages 18 to 65 with a diagnosis of bipolar I disorder manic or mixed with or without psychotic features will be randomized to double-blind treatment to receive either TAM 20-140 mgday or placebo for a period of 3 weeks Following this acute period the patients will receive either open-label TAM or treatment as clinically indicated Approximately 50 patients with acute mania will be enrolled in the study Biochemical measures will be obtained during the study
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 |
|---|---|---|---|
| 02-M-0037 | None | None | None |