The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder

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

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.

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.

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.

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 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.

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").

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.

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.