CoQ10 in Geriatric Bipolar Depression

This study has been completed.
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Brent Forester, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT00720369
First received: July 18, 2008
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

We propose to study and compare measures of brain energy metabolism in geriatric bipolar individuals and healthy older adults. We would also like to investigate changes in brain energy metabolites and in vivo creatine kinase (CK) enzymatic activity associated with CoQ10 administration in older bipolar individuals.


Condition Intervention
Bipolar Depression
Drug: CoEnzyme Q10

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Oral Administration of CoQ10 and Phosphorus-31 Magnetization Transfer Magnetic Resonance Spectroscopy in Geriatric Bipolar Disorder and Healthy Older Adults

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • We Measured the Change in Rate Constant of Creatine Kinase in Individuals With Bipolar Depression Treated With CoQ 10 as Compared With Age and Gender Matched Controls. These Rate Constants Were Calculated Using Magnetic Resonance Imaging (MRI). [ Time Frame: 8 week trial ] [ Designated as safety issue: No ]
    The rate constant for creatine kinase is a measurement of the reaction rate ADP+PCr <---> ATP + Cr, which is catalyzed by the enzyme creatine kinase. The rate constant shows the direction and magnitude of the reaction at equilibrium. A higher rate constant indicates a higher rate constant of the CK enzyme, meaning, more efficient/rapid conversion of PCr to ATP through the creatine kinase enzymatic reaction in tissues with high and fluctuating energy demands such as brain and muscle tissue. As the value is a reaction rate, there are no associated units.


Secondary Outcome Measures:
  • We Measured Response to Treatment of Depression (Using the Montgomery Asberg Depression Rating Scale)in Older Adults With Bipolar Disorder After an 8 Week Trial of CoQ10. [ Time Frame: 8 week trial ] [ Designated as safety issue: No ]

    The Montgomery Asberg Depression Rating Scale (MADRS) is a 10 question questionnaire which assesses symptom severity of depression. The score is on a 0-60 scale with higher numbers indicating more severe depressive symptoms. The score is represented as a number of points.

    Clinical improvement following treatment with CoQ10 supplement was only tested in the Bipolar subject cohort, not in healthy controls, therefore outcome data only apply to the bipolar group.



Enrollment: 42
Study Start Date: July 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CoEnzyme Q10
Open Label Study
Drug: CoEnzyme Q10
CoEnzyme Q10 with dosage range from 400 mg to 1200 mg per day
No Intervention: Healthy Controls
Healthy controls completed all study procedures completed by the CoQ10 group but did not receive any study medication.

Detailed Description:

Hypotheses

  1. At baseline, the forward rate constant (kfor) of CK enzymatic activity in the frontal lobe of older subjects with bipolar depression will be significantly decreased relative to that of age-matched healthy controls.
  2. After 8 weeks of treatment, bipolar depression subjects will demonstrate an increase in the kfor of CK after 8 weeks of CoQ 10 treatment.
  3. Increases in the CK forward rate constant (kfor) will correlate with improvement in subjects' mood state as assessed by the Montgomery Asberg Depression Rating Scale (MADRS).
  4. Baseline measures of executive functioning and information processing speed (measured by performance on the Wisconsin Card Sorting Test (WCST), Trails A and B and Stroop tests) will be impaired in subjects with geriatric bipolar depression compared with healthy controls. These measures will improve with successful treatment with CoQ10 and correlate with increases in the CK forward rate constant (kfor).

Summary:

A review of literature suggests a distinct pattern of bioenergetic changes, possibly related to mitochondrial dysfunction and abnormal CK function, in older adults and in individuals with bipolar disorder. As opposed to rudimentary measurements of static metabolite concentrations, the novel use of MT-MRS in such individuals will offer insight into the enzyme kinetics of CK, specifically examining the rate at which ATP is formed from PCr. From previous investigations it would seem that the dietary-supplement, CoQ10, is able to improve the efficiency of mitochondrial function in subjects with altered bioenergetics. We propose to measure CK activity and PCr turnover rate before and after CoQ10 treatment, with the overall aim of understanding metabolic relationships between brain bioenergetic alterations and treatment with CoQ10 in geriatric bipolar depression.

  Eligibility

Ages Eligible for Study:   55 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 55 years or older
  • Meet DSM-IV diagnostic criteria for Bipolar Disorder, Current Episode Depressed
  • Montgomery Asberg Depression Rating Scale (MADRS) Score of >20
  • If the MADRS score is <20 but >16, a diagnosis of bipolar disorder, current episode depressed, based on the Structured Clinical Interview of DSM IV TR (SCID) and Dr. Forester's initial interview would allow the subject to be included in the study.
  • Young Mania Rating Scale (YMRS) Score of < 6
  • If the YMRS score is >6 subjects can still be admitted if subjects do not meet clinical criteria for mania or hypomania at the time of screening
  • Able to provide informed consent
  • Must speak English
  • Must be able to visit McLean Hospital for the screening visit and six study visits during the 8-week duration of the study
  • Subjects may be taking other medications for bipolar depression including antidepressants, mood stabilizers and antipsychotic mediations prior to Co-Q10 therapy, but may not have any dosage adjustments of these medications in the week before Co-Q10 is added.

Exclusion Criteria:

  • Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease
  • History of seizure disorder,
  • History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, unipolar major depressive disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months.
  • History of drug hypersensitivity or intolerance to Coenzyme Q10.
  • Use of medications that are excluded in this study (barbiturates; however, the use of non-benzodiazepine sedative hypnotics (such as zolpidem (Ambien)) may be used as needed except within 12 hours of the MRI scan)
  • Benzodiazepines may be used by subjects throughout the study as long as they are not taken within 12 hours of any MRI scan.
  • Subjects diagnosed with a mitochondrial disorder.
  • Subjects taking other putative mitochondrial enhancers (e.g., vitamin E, carnitine, creatine, Vitamin complex B, pramipexole) at the time of study entry.
  • Any of the exclusion criteria mentioned in the MRI risks section below
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720369

Locations
United States, Massachusetts
McLean Hospital
Belmont, Massachusetts, United States, 02478
Sponsors and Collaborators
Mclean Hospital
National Alliance for Research on Schizophrenia and Depression
Investigators
Principal Investigator: Brent P Forester, MD Mclean Hospital
  More Information

No publications provided

Responsible Party: Brent Forester, Director, Mood Disorders Division, Geriatric Psychiatry Research Program, Mclean Hospital
ClinicalTrials.gov Identifier: NCT00720369     History of Changes
Other Study ID Numbers: 2008-P-000738/1
Study First Received: July 18, 2008
Results First Received: September 20, 2011
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mclean Hospital:
Bipolar depression
elderly
Coenzyme Q10
Magnetic resonance spectroscopy

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Coenzyme Q10
Ubiquinone
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Vitamins

ClinicalTrials.gov processed this record on July 22, 2014