The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Bipolar Depression

Intervention / Treatment
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* Drug: acetyl-l-carnitine PLUS alpha-lipoic acide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>1000-3000mg/day of acetyl-l-carnitine PLUS 600-1800mg/day of alpha-lipoic acid | Drug: acetyl-l-carnitine PLUS alpha-lipoic acide<br>* 1000-3000 mg/day of acetyl-l-carnitine in addition to 600-1800 mg/day of alpha-lipoic acid.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The 25-Item Hamilton Depression Rating Scale. | 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. | Baseline to 15 Weeks | 
| The Montgomery-Asberg Depression Rating Scale | 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. | Baseline to 15 weeks | 
| The Young Mania Rating Scale | 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. | Baseline to 15 weeks | 
| Clinical Global Impression-Severity | 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). | Baseline to 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phosphorus MRS Scans on 4T Scanner | 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. | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar disorder, Bipolar depression, Natural substances, Depression