Mitochondrial Dysfunction in the Pathophysiology and Treatment of Bipolar Disorder

NCT00327756 | Withdrawn Phase 2

• 2 other identifiers: 06016206-M-0162
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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 Parkinson's 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. ...

Conditions

Bipolar Affective Disorder; Depression

Keywords

Depression; Magnetic Resonance Spectroscopy; Mitochondrial Enhancer; Manic Depressive; Bioenergetics; Bipolar Disorder; Manic Depression

Outcome Measures

Primary Outcomes (1)

• Compare brain lactate levels between healthy controls and subjects with bipolar depression and assess in subjects w/bipolar depression the effect of of CoQ10 admin compared to placebo on the brain lactate signal obtained w/MRS w/photic stimulation.

  8 weeks

Secondary Outcomes (1)

• To determine the antidepressant efficacy of CoQ10 compared to placebo in depressed subjects w/bipolar disorder by using the mean change in MADRS total score pre- and post-study.

  8-weeks

Interventions

Coenzyme Q10 DRUG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, 18 to 65 years of age.
• Female subjects of childbearing potential must be using a medically accepted means of contraception.
• Each subject must understand the nature of the study and must sign an informed consent document.
• Subjects must fulfill the criteria for Bipolar disorder depressed without psychotic features including rapid cycling as defined in DSM-IV based on clinical assessment and confirmed by structured diagnostic interview SCID-P.
• Subjects must have an initial score at Visit 1 and Visit 2 of at least 16 on the MADRS
• In bipolar II disorder, subjects must have experienced, in the opinion of the investigator, at least two previous hypomanic and two major depressive episodes as defined in DSM-IV.
• Current major depressive episode at least 4 weeks in duration.

You may not qualify if:

• Subjects who are currently on a mood stabilizer for maintenance treatment and are benefiting from it.
• Current diagnosis of primary anxiety disorder necessitating treatment (subjects with OCD will be excluded).
• Presence of psychotic features
• Participation in a clinical trial of another investigational drug within 1 month prior to study entry (Visit 1).
• Female subjects who are either pregnant or nursing.
• Serious, unstable illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinology, neurological, immunologic, or hematological disease.
• Subjects diagnosed with a mitochondrial disorder.
• Subjects taking other putative mitochondrial enhancers (e.g., vitamin E, carnitine, creatine, Vit complex B, pramipexole; see Appendix B) by the time of randomization (Visit 2).
• Subjects taking Statins
• Subjects with Diabetes Mellitus (Type I and Type II)
• Subjects with a history of clotting disorders or needing anticoagulants e.g. warfarin.
• Subjects with history of deep vein thrombosis or the following risk factors for DVTs, smoking and/or contraceptives (30 days before Visit 2).
• Subjects with uncorrected hypothyroidism or hyperthyroidism.
• Subjects with one or more seizures.
• Documented history of hypersensitivity or intolerance to CoQ10.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Arias-Mendoza F. In vivo magnetic resonance spectroscopy in the evaluation of mitochondrial disorders. Mitochondrion. 2004 Sep;4(5-6):491-501. doi: 10.1016/j.mito.2004.07.034. Epub 2004 Sep 30.

  PMID: 16120408 BACKGROUND

• Baker SK, Tarnopolsky MA. Targeting cellular energy production in neurological disorders. Expert Opin Investig Drugs. 2003 Oct;12(10):1655-79. doi: 10.1517/13543784.12.10.1655.

  PMID: 14519086 BACKGROUND

• Bertolino A, Frye M, Callicott JH, Mattay VS, Rakow R, Shelton-Repella J, Post R, Weinberger DR. Neuronal pathology in the hippocampal area of patients with bipolar disorder: a study with proton magnetic resonance spectroscopic imaging. Biol Psychiatry. 2003 May 15;53(10):906-13. doi: 10.1016/s0006-3223(02)01911-x.

  PMID: 12742678 BACKGROUND

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

coenzyme Q10

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 18, 2006
• First Posted: May 19, 2006
• Study Start: May 1, 2006
• Primary Completion: May 1, 2009
• Last Updated: November 23, 2011

Record last verified: 2009-05

Locations

US (1)