Bipolar Disorder
Conditions
Keywords
bipolar disorder, mood disorders, manic depression, nutrition
Brief summary
The purpose of the trial was to determine whether a 36-ingredient micronutrient supplement (primarily vitamins and minerals) is beneficial for the treatment of bipolar disorder, when studied under randomized and fully blinded conditions and compared to a placebo. The supplement is referred to as MCN36, because it contains 36 nutrients. Based on the preliminary research on this supplement, it is hypothesized that patients who take MCN36 for 8 weeks will experience improved mood stability relative to those who take the placebo. All participants must live EITHER in the vicinity of Calgary, Alberta, Canada, OR in the area of San Diego, California.
Detailed description
This RCT (randomized clinical trial) compared MCN36 to placebo in patients randomized to receive one or the other for 8 weeks. Close medical supervision was provided with weekly appointments. At the end of the 8 weeks, all participants were offered the opportunity of entering an 8-week open-label extension. The efficacy objective of this study was to assess the efficacy of MCN36 compared with placebo in otherwise medication-free adults with bipolar disorder I and II, in improving overall symptomatology at the end of 8 weeks of therapy as assessed under randomized and fully blinded conditions * as measured by the clinician using the Overall Bipolarity Index (OBI) (primary outcome measure). * as measured by the clinician using the Clinical Global Impressions for Bipolar Disorder (CGI-BP) for Severity. * as measured by self-report recorded on the Outcome Questionnaire (OQ). * in terms of rate of response, with response defined as a reduction of 50% or more in either the depression or the mood elevation component of the OBI. * in terms of functional states and health-related quality of life as measured by The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). The safety-related objective was to assess the safety of MCN36 compared with placebo in terms of * laboratory analyses * treatment-emergent adverse events, which will be solicited at each appointment using the Adverse Event Log. Participants had two appointments for screening and confirming suitability for the trial. Between those two appointments, they provided a blood sample, and met with a research nurse. They also kept a 7-day food record of their food intake prior to the second appointment. If suitability was confirmed at the second visit, they entered the randomized phase.
Interventions
DRUGMCN36 (nutritional supplement)
nutritional supplement
DRUGPlacebo
nutritional supplement
Sponsors
Alberta Innovation and Science
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must meet the criteria for bipolar disorder I or II as defined in DSM-IV-TR based on clinical assessment and confirmed by structured diagnostic interview (SCID-P). * Must be symptomatic on the Hamilton Depression Scale and the Young Mania Rating Scale * Must be free of medications or herbal/nutritional supplements with primarily central nervous system activity * Must be able to eat at least a snack three times per day, so that the capsules will not be ingested on an empty stomach
Exclusion criteria
* Current or lifetime diagnosis of any of the following according to DSM-IV-TR criteria: Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, Delusional Disorder, Psychotic Disorder Not Otherwise Specified, Delirium of any type, Dementia of any type, Amnestic Disorder, unless there is substantive reason to believe the patient was misdiagnosed. * Alcohol dependence or abuse in the previous six months. * Dependence or abuse of substances other than alcohol in the previous two years. * Any Psychotic Disorder due to a General Medical Condition in the previous two years * Hospitalization for treatment of a mental disorder within the previous 6 months. * Current use of any other medication or herbal/nutritional supplement with primarily central nervous system activity. * Neurological disorder involving brain or other central function. * Severe headaches of any type (including migraine) within the previous 3 months. * Unstable illnesses either with active significant symptoms or requiring medication changes within the previous 4 months. * Abnormal laboratory values detected at screening, in particular an ALT or AST greater than 2 times the upper limit of normal, or creatinine greater than 1.75 times the upper limit of normal. * Uncorrected or unstable hypothyroidism or hyperthyroidism in the previous 12 months. * Medically diagnosed Irritable Bowel Syndrome, or any other chronic gastrointestinal problem, within the previous 3 years. * Current or lifetime metabolic disorder or problem, such as phenylketonuria or Wilson's disease. * A course of treatment with electroconvulsive therapy (ECT) within the previous 12 months, or a lifetime history of four or more courses of ECT. * Current bacterial, viral, fungal, parasite or other infection. * Women who are pregnant or breast-feeding; women of childbearing potential who are not using a medically accepted means of contraception when engaging in sexual intercourse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mood as Evaluated by the Overall Bipolarity Index (Composite of the Hamilton Depression Scale and the Young Mania Rating Scale) | Baseline to 8 weeks | Change in mood from baseline to final visit, as evaluated by the Overall Bipolarity Index (composite of the Hamilton Depression Scale and the Young Mania Rating Scale); minimum possible score is 0 and maximum possible score is 103; higher scores mean worse symptomatology |
Secondary
| Measure | Time frame |
|---|---|
| Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) | Baseline to 8 weeks |
| Global Clinical Impressions | Baseline to 8 weeks |
| Outcome Questionnaire --- a Self-report Questionnaire | Baseline to 8 weeks |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Comparator Placebo comparator | 20 |
| Micronutrient Formula nutritional supplement | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo Comparator | Micronutrient Formula | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 40 Participants |
| Age Continuous | 40 years STANDARD_DEVIATION 13 | 35 years STANDARD_DEVIATION 9 | 37.5 years STANDARD_DEVIATION 11 |
| Region of Enrollment Canada | 16 participants | 17 participants | 33 participants |
| Region of Enrollment United States | 4 participants | 3 participants | 7 participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Mood as Evaluated by the Overall Bipolarity Index (Composite of the Hamilton Depression Scale and the Young Mania Rating Scale)
Change in mood from baseline to final visit, as evaluated by the Overall Bipolarity Index (composite of the Hamilton Depression Scale and the Young Mania Rating Scale); minimum possible score is 0 and maximum possible score is 103; higher scores mean worse symptomatology
Time frame: Baseline to 8 weeks
Population: All participants were included, since the analysis was intent-to-treat with last observation carried forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Comparator | Mood as Evaluated by the Overall Bipolarity Index (Composite of the Hamilton Depression Scale and the Young Mania Rating Scale) | -21.1 units on a scale | Standard Deviation 3.4 |
| Micronutrient Formula | Mood as Evaluated by the Overall Bipolarity Index (Composite of the Hamilton Depression Scale and the Young Mania Rating Scale) | -18.9 units on a scale | Standard Deviation 2.9 |
Secondary
Global Clinical Impressions
Time frame: Baseline to 8 weeks
Secondary
Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)
Time frame: Baseline to 8 weeks
Secondary
Outcome Questionnaire --- a Self-report Questionnaire
Time frame: Baseline to 8 weeks