Ignite Creation Date:
2024-05-05 @ 4:49 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00327756
Status:
WITHDRAWN
Last Update Posted:
2011-11-23
First Post:
2006-05-18
Brief Title:
Mitochondrial Dysfunction in the Pathophysiology and Treatment of Bipolar Disorder
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
An Investigation Examining the Evidence for Mitochondrial Dysfunction in the Pathophysiology and Treatment of Bipolar Disorder
Status:
WITHDRAWN
Status Verified Date:
2009-05
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 examine whether mitochondrial function is impaired in patients with bipolar disorder Mitrochondria are small organelles inside the cell that are responsible for energy production Recent studies in animals and humans suggest that abnormalities of mitrochondria may be involved in bipolar depression The study will also examine whether the food supplement Coenzyme Q10 CoQ10 improves mitochondrial function and symptoms such as depressed mood low energy anxiety or slowness in thinking and movements in bipolar patients CoQ10 has been used to increase cell energy production and as an antioxidant It has had some benefit in patients with Parkinsons disease and migraine and in prolonging survival in patients with cancer and heart failure
Patients 18-65 years of age with bipolar disorder who are currently in a depressive episode of at least 4 weeks duration may be eligible for this study The study has four phases as follows
Phase I Medication Withdrawal
Patients taper off all psychotropic medications usually over 1 to 2 weeks
Phase II Baseline Evaluation
After being off all medication for about 2 weeks patients undergo the following procedures
Magnetic resonance imaging MRI and magnetic resonance spectroscopy MRS The two procedures are performed in an MRI scanner Both tests use a strong magnetic field and radio waves to obtain images that provide information on brain anatomy and chemistry
Blood tests to assess mitochondrial function isolated from blood cells
Skin biopsy for tests of mitochondria A small sample of skin tissue 5 x 5 millimeters is surgically removed
Phase III Administration of CoQ10 or Placebo
Participants are randomly assigned to take either CoQ10 or placebo an inactive look-alike substance twice a day by mouth While taking the study medication patients have the following procedures periodically
Rating scales for anxiety and depression and adverse events
Check of vital signs
Blood and urine sample collections
Phase IV Study Completion
At the end of the 8 weeks of treatment patients have a physical examination and electrocardiogram and the procedures in phase II are repeated Participants may then receive short-term treatment up to 12 weeks with medications for bipolar depression followed by referred to a community physician for long-term treatment
Patients 18-65 years of age with bipolar disorder who are currently in a depressive episode of at least 4 weeks duration may be eligible for this study The study has four phases as follows
Phase I Medication Withdrawal
Patients taper off all psychotropic medications usually over 1 to 2 weeks
Phase II Baseline Evaluation
After being off all medication for about 2 weeks patients undergo the following procedures
Magnetic resonance imaging MRI and magnetic resonance spectroscopy MRS The two procedures are performed in an MRI scanner Both tests use a strong magnetic field and radio waves to obtain images that provide information on brain anatomy and chemistry
Blood tests to assess mitochondrial function isolated from blood cells
Skin biopsy for tests of mitochondria A small sample of skin tissue 5 x 5 millimeters is surgically removed
Phase III Administration of CoQ10 or Placebo
Participants are randomly assigned to take either CoQ10 or placebo an inactive look-alike substance twice a day by mouth While taking the study medication patients have the following procedures periodically
Rating scales for anxiety and depression and adverse events
Check of vital signs
Blood and urine sample collections
Phase IV Study Completion
At the end of the 8 weeks of treatment patients have a physical examination and electrocardiogram and the procedures in phase II are repeated Participants may then receive short-term treatment up to 12 weeks with medications for bipolar depression followed by referred to a community physician for long-term treatment
Detailed Description:
Bipolar affective disorder is a common severe chronic and often life-threatening illness The depressive phase contributes to the majority of morbidity and mortality in this illness Impairments in physical and social functioning resulting from depression are often as severe as other chronic medical illnesses Few of the treatments in use have resulted from an understanding of the pathophysiology of bipolar disorder Undoubtedly a greater understanding of the pathophysiology of bipolar disorder will lead to improved treatments
Current theories of depression suggest that mood disorders are associated with impairments of cellular resilience and structural plasticity possibly a result of abnormal cellular energy metabolism Studies with Magnetic Resonance Spectroscopy MRS in bipolar subjects show reduced brain intracellular pH and reduced ATP Cellular energy generated by mitochondrial oxidative phosphorylation from glucose via the electron transport chain is stored as ATP which provide neurons and glia with energy required to maintain their function Mitochondrial dysfunction and its inability to compensate for increase in ATP demand might lead to impaired cellular resilience believed to be involved in the pathophysiology of bipolar disorder Abnormal regulation of nuclear genes coding for mitochondrial proteins in the hippocampus of bipolar subjects provides further evidence of mitochondrial dysfunction in bipolar disorder
Coenzyme Q10 CoQ10 is an essential cofactor in the mitochondrial electron transport chain necessary for cellular energy generation Exogenous administration of CoQ10 attenuates ATP depletion and has anti-oxidant properties In light of the above evidence we hypothesize that bipolar disorder is associated with mitochondrial dysfunction as evidenced by impaired brain energy metabolism and that administration of CoQ10 a mitochondrial enhancer will restore mitochondrial function To accomplish these objectives we will compare mitochondrial functions in bipolar depressed subjects to 26 healthy controls matched for age gender and BMI Measures of mitochondrial function will include brain lactate levels a product of anaerobic glycolysis with H MRS 2 assays of mitochondrial function in cultured fibroblasts and platelets and 3 gene expression of mitochondrial and nuclear genes using a cDNA Microarray Further subjects with bipolar depression ages 18 to 65 will be randomized to either CoQ10 300-1200 mgday or placebo in a double-blind placebo controlled trial for a period of 8 weeks Measures of mitochondrial function will be compared between subjects randomized to placebo or CoQ10 at baseline and at the end of the 8-week trial
Current theories of depression suggest that mood disorders are associated with impairments of cellular resilience and structural plasticity possibly a result of abnormal cellular energy metabolism Studies with Magnetic Resonance Spectroscopy MRS in bipolar subjects show reduced brain intracellular pH and reduced ATP Cellular energy generated by mitochondrial oxidative phosphorylation from glucose via the electron transport chain is stored as ATP which provide neurons and glia with energy required to maintain their function Mitochondrial dysfunction and its inability to compensate for increase in ATP demand might lead to impaired cellular resilience believed to be involved in the pathophysiology of bipolar disorder Abnormal regulation of nuclear genes coding for mitochondrial proteins in the hippocampus of bipolar subjects provides further evidence of mitochondrial dysfunction in bipolar disorder
Coenzyme Q10 CoQ10 is an essential cofactor in the mitochondrial electron transport chain necessary for cellular energy generation Exogenous administration of CoQ10 attenuates ATP depletion and has anti-oxidant properties In light of the above evidence we hypothesize that bipolar disorder is associated with mitochondrial dysfunction as evidenced by impaired brain energy metabolism and that administration of CoQ10 a mitochondrial enhancer will restore mitochondrial function To accomplish these objectives we will compare mitochondrial functions in bipolar depressed subjects to 26 healthy controls matched for age gender and BMI Measures of mitochondrial function will include brain lactate levels a product of anaerobic glycolysis with H MRS 2 assays of mitochondrial function in cultured fibroblasts and platelets and 3 gene expression of mitochondrial and nuclear genes using a cDNA Microarray Further subjects with bipolar depression ages 18 to 65 will be randomized to either CoQ10 300-1200 mgday or placebo in a double-blind placebo controlled trial for a period of 8 weeks Measures of mitochondrial function will be compared between subjects randomized to placebo or CoQ10 at baseline and at the end of the 8-week trial
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-0162 | None | None | None |