The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder

This study has been completed.
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
Brian P. Brennan, MD, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT00719706
First received: July 18, 2008
Last updated: June 13, 2012
Last verified: June 2012
  Purpose

The primary objective of this 15-week clinical trial is to test the hypothesis that treatment with two proven mitochondrial enhancers, acetyl-L-carnitine (ALCAR) and α-lipoic acid (ALA), has significantly greater efficacy than placebo as an augmentation treatment in bipolar depressed patients who display an incomplete response to conventional treatments.


Condition Intervention Phase
Bipolar Depression
Drug: acetyl-l-carnitine PLUS alpha-lipoic acide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder: A Randomized, Placebo-Controlled Trial of Acetyl-L-Carnitine and Alpha-Lipoic Acid for the Treatment of Bipolar Depression

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • The 25-Item Hamilton Depression Rating Scale. [ Time Frame: Baseline to 15 Weeks ] [ Designated as safety issue: No ]
    Scores could range from 0 - 72 units on a scale, with 0 representing the least number of depressive symptoms and 72 representing the most number of depressive symptoms.

  • The Montgomery-Asberg Depression Rating Scale [ Time Frame: Baseline to 15 weeks ] [ Designated as safety issue: No ]
    Scores could range from 0 - 60 units on a scale with 0 representing the least number of depressive symptoms and 60 representing the most number of depressive symptoms.

  • The Young Mania Rating Scale [ Time Frame: Baseline to 15 weeks ] [ Designated as safety issue: No ]
    The scores could range from 0 - 60 units on a scale with 0 representing the least number of manic symptoms and 60 representing the most number of manic symptoms.

  • Clinical Global Impression-Severity [ Time Frame: Baseline to 15 weeks ] [ Designated as safety issue: No ]
    Scores could range from 0 - 7 units on a scale, with 0 representing the least severe ("Normal, not at all ill") and 7 representing the most severe ("Among the most extremely ill patients").


Secondary Outcome Measures:
  • Phosphorus MRS Scans on 4T Scanner [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Whole brain total NTP levels as measured by a phosphorus MRS scan on the 4T scanner. The data could range from 0 - 1, with 0 representing the lowest NTP level and 1 representing the highest NTP level.


Enrollment: 40
Study Start Date: August 2008
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
1000-3000mg/day of acetyl-l-carnitine PLUS 600-1800mg/day of alpha-lipoic acid
Drug: acetyl-l-carnitine PLUS alpha-lipoic acide
1000-3000 mg/day of acetyl-l-carnitine in addition to 600-1800 mg/day of alpha-lipoic acid.
Placebo Comparator: 2 Drug: Placebo
Placebo

Detailed Description:

The primary objective of this proposed clinical trial is to test the hypothesis that treatment with two proven mitochondrial enhancers, acetyl-L-carnitine (ALCAR) and α-lipoic acid (ALA), has significantly greater efficacy than placebo as an augmentation treatment in bipolar depressed patients who display an incomplete response to conventional treatments. We propose to test this hypothesis by performing a 15-week placebo-controlled, double-blind, parallel group, flexible-dose study investigating the use of ALCAR and ALA as an augmentation to treatment as usual in depressed bipolar patients. We will compare the efficacy of acetyl-l-carnitine (ALCAR) at doses of 1000-3000mg/day and alpha-lipoic acid (ALA) at doses of 600-1800mg/day with placebo on symptom improvement in individuals diagnosed with bipolar disorder type I, current episode depressed. Improvement will be assessed using the 21-Item Hamilton Depression Rating Scale (HAM-D), the Montgomery Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression-Severity and Improvement Scales (CGI-S and CGI-I).

Furthermore, we hypothesize that improvement in depression symptoms following treatment with ALCAR and ALA will be associated with increases in phosphocreatine (PCr), beta-nucleoside triphosphate (β-NTP), and intracellular pH in the anterior cingulate cortex (ACC) both at week 1 and week 12 of treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female age 18-65 years.
  • Meets DSM-IV criteria for Bipolar Disorder, type I with current episode depressed.
  • Current score of greater than or equal to 18 on the 21-Item Hamilton Depression Rating Scale at Visits 1 and 2.
  • Maintained on a stable treatment regimen with no changes in medication dosages for at least two weeks prior to study entry.

Exclusion Criteria:

  • Unwilling or unable to provide informed consent
  • Score of greater than or equal to 12 on the Young Mania Rating Scale at Visit 1 or 2.
  • Current suicidal or homicidal ideation.
  • Active psychotic symptoms.
  • Lifetime history of schizophrenia or obsessive-compulsive disorder.
  • DSM-IV diagnosis of alcohol or substance dependence in the 3 months prior to screening.
  • Clinically significant medical condition that would interfere with study participation.
  • History of hypersensitivity to ACLCAR or ALA.
  • Pregnant or lactating.
  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: NCT00719706

Locations
United States, Massachusetts
McLean Hospital
Belmont, Massachusetts, United States, 02478
Sponsors and Collaborators
Mclean Hospital
Stanley Medical Research Institute
Investigators
Principal Investigator: Brian P Brennan, MD Mclean Hospital
  More Information

No publications provided

Responsible Party: Brian P. Brennan, MD, Associate Director of Translational Neuroscience Research, Mclean Hospital
ClinicalTrials.gov Identifier: NCT00719706     History of Changes
Other Study ID Numbers: 2008-P-000772
Study First Received: July 18, 2008
Results First Received: June 13, 2012
Last Updated: June 13, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mclean Hospital:
Bipolar disorder
Bipolar depression
Natural substances
Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Affective Disorders, Psychotic
Carnitine
Acetylcarnitine
Thioctic Acid
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on October 19, 2014