Clinical trial NCT00719706: The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bipolar Depression
Keywords: Bipolar disorder
Bipolar depression
Natural substances
Depression
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2008-07-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: The 25-Item Hamilton Depression Rating Scale.
timeFrame: Baseline to 15 Weeks
measure: The Montgomery-Asberg Depression Rating Scale
timeFrame: Baseline to 15 weeks
measure: The Young Mania Rating Scale
timeFrame: Baseline to 15 weeks
measure: Clinical Global Impression-Severity
timeFrame: Baseline to 15 weeks
Secondary outcomes:
measure: Phosphorus MRS Scans on 4T Scanner
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
Study officials:
affiliation: Mclean Hospital
name: Brian P Brennan, MD
role: PRINCIPAL_INVESTIGATOR
References: