The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder

Phase 2

Completed

Interventions: Drug: acetyl-l-carnitine PLUS alpha-lipoic acide
Drug: Placebo

Brief Summary: 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.

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
1	acetyl-l-carnitine PLUS alpha-lipoic acide	1000-3000mg/day of acetyl-l-carnitine PLUS 600-1800mg/day of alpha-lipoic acid
2	Placebo	-

Primary Outcome Measures

Name	Time	Method
The 25-Item Hamilton Depression Rating Scale.	Baseline to 15 Weeks	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	Baseline to 15 weeks	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	Baseline to 15 weeks	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	Baseline to 15 weeks	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

Name	Time	Method
Phosphorus MRS Scans on 4T Scanner	Baseline to 12 weeks	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.