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| Name | Class |
|---|---|
| Stanley Medical Research Institute | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | 1000-3000mg/day of acetyl-l-carnitine PLUS 600-1800mg/day of alpha-lipoic acid |
|
| 2 | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| acetyl-l-carnitine PLUS alpha-lipoic acide | Drug | 1000-3000 mg/day of acetyl-l-carnitine in addition to 600-1800 mg/day of alpha-lipoic acid. |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brian P Brennan, MD | Mclean Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McLean Hospital | Belmont | Massachusetts | 02478 | United States |
To limit heterogeneity in the imaging sample, we accepted only type I bipolar disorder participants for the imaging component of the study.
Recruitment began in August 2008 and ended in May 2011 and took place at a research lab within McLean hospital.
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| ID | Title | Description |
|---|---|---|
| FG000 | ALCAR/ALA | Participants taking 1000-3000mg/day of acetyl-l-carnitine PLUS 600-1800mg/day of alpha-lipoic acid. |
| FG001 | Placebo | Participants taking placebo. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ALCAR/ALA | Participants taking 1000-3000mg/day of acetyl-l-carnitine PLUS 600-1800mg/day of alpha-lipoic acid. |
| BG001 | Placebo | Participants taking placebo. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | At baseline, the number of participants analyzed was the number randomized into the study. At endpoint, the number or participants analyzed is the last observation carried forward of the original 20 participants. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 15 Weeks |
|
Baseline to 13 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ALCAR/ALA | Participants taking 1000-3000mg/day of acetyl-l-carnitine PLUS 600-1800mg/day of alpha-lipoic acid. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Brian Brennan | McLean Hospital | 617-855-2911 | bbrennan@partners.org |
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| D003863 | Depression |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
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| ID | Term |
|---|---|
| D000108 | Acetylcarnitine |
| ID | Term |
|---|---|
| D002331 | Carnitine |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
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| Placebo | Drug | Placebo |
|
| Protocol Violation |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Participants taking placebo.
|
|
| Primary | 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. | At baseline, the number of participants analyzed was the number randomized into the study. At endpoint, the number or participants analyzed is the last observation carried forward of the original 20 participants. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 15 weeks |
|
|
|
| Primary | 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. | At baseline, the number of participants analyzed was the number randomized into the study. At endpoint, the number or participants analyzed is the last observation carried forward of the original 20 participants. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 15 weeks |
|
|
|
| Primary | 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"). | At baseline, the number of participants analyzed was the number randomized into the study. At endpoint, the number or participants analyzed is the last observation carried forward of the original 20 participants. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 15 weeks |
|
|
|
| Secondary | 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. | At baseline, the number of participants analyzed was the number entered into the imaging portion of the study. At endpoint, the number or participants analyzed is the last observation carried forward of the original 10 participants in each category. | Posted | Mean | Standard Deviation | units on a scale | Baseline to 12 weeks |
|
|
|
| 0 |
| 20 |
| 20 |
| 20 |
| EG001 | Placebo | Participants taking placebo. | 0 | 20 | 19 | 20 |
| foul-smelling urine | Renal and urinary disorders | Systematic Assessment |
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| rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| constipation | Gastrointestinal disorders | Systematic Assessment |
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| dyspepsia | Gastrointestinal disorders | Systematic Assessment |
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| nausea | Gastrointestinal disorders | Systematic Assessment |
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| abdominal cramping | Gastrointestinal disorders | Systematic Assessment |
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| chest pain | Cardiac disorders | Systematic Assessment |
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| restlessness | General disorders | Systematic Assessment |
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| pruritis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| vomiting | Gastrointestinal disorders | Systematic Assessment |
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| sedation | General disorders | Systematic Assessment |
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| upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| dry mouth | General disorders | Systematic Assessment |
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| insomnia | General disorders | Systematic Assessment |
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| flu-like illness | Gastrointestinal disorders | Systematic Assessment |
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| fatigue | General disorders | Systematic Assessment |
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| headache | General disorders | Systematic Assessment |
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| blood in stool | Gastrointestinal disorders | Systematic Assessment |
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| blurred vision | Eye disorders | Systematic Assessment |
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| word-finding difficulties | Psychiatric disorders | Systematic Assessment |
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| hirsuitism | Endocrine disorders | Systematic Assessment |
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| facial flushing | Vascular disorders | Systematic Assessment |
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| decreased taste | General disorders | Systematic Assessment |
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| salty taste | General disorders | Systematic Assessment |
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| nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| dizziness | General disorders | Systematic Assessment |
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| flatulence | Gastrointestinal disorders | Systematic Assessment |
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| anxiety | Psychiatric disorders | Systematic Assessment |
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| sore throat | General disorders | Systematic Assessment |
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| facial acne | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| irritability | Psychiatric disorders | Systematic Assessment |
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| bloating | Gastrointestinal disorders | Systematic Assessment |
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| weight gain | General disorders | Systematic Assessment |
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| tremor | General disorders | Systematic Assessment |
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| urinary frequency | Renal and urinary disorders | Systematic Assessment |
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| D001519 |
| Behavior |
| D009930 |
| Organic Chemicals |
| Endpoint Data |
|