The purpose of the trial is 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.

Condition	Treatment or Intervention	Phase
Bipolar Disorder	Drug: MCN36 (nutritional supplement)	Phase II

Further Study Details: 

Primary Outcomes: Mood as evaluated by the Overall Bipolarity Index (composite of the Hamilton Depression Scale and the Young Mania Rating Scale)
Secondary Outcomes: Global Clinical Impressions; Outcome Questionnaire --- a self-report questionnaire; Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)
Expected Total Enrollment:  96

This RCT (randomized clinical trial) will compare MCN36 to placebo in patients randomized to receive one or the other for 8 weeks. Close medical supervision will be provided with weekly appointments. At the end of the 8 weeks, all participants will be offered the opportunity of entering an 8-week open-label extension.

The efficacy objective of this study is 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 is 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 will have two appointments for screening and confirming suitability for the trial. Between those two appointments, they will provide a blood sample, and will meet with a research nurse. They will also keep a 7-day food record of their food intake prior to the second appointment. If suitability is confirmed at the second visit, they will enter the randomized phase.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

Please refer to this study by ClinicalTrials.gov identifier  NCT00109577

Bonnie J Kaplan, PhD      403-943-7363    bonnie.kaplan@calgaryhealthregion.ca
J. Steven A Simpson, PhD, MD      403-944-1272    steve.simpson@calgaryhealthregion.ca

Canada, Alberta
      University of Calgary Faculty of Medicine, Calgary,  Alberta,  T2N 4N1,  Canada; Recruiting

Study chairs or principal investigators

Bonnie J Kaplan, PhD,  Principal Investigator,  University of Calgary   

Study ID Numbers:  18229; AIS99-03A (01406-005-23)
Record last reviewed:  April 2005
Last Updated:  April 29, 2005
Record first received:  April 28, 2005
ClinicalTrials.gov Identifier:  NCT00109577
Health Authority: Canada: Health Canada (Awaiting confirmation)
ClinicalTrials.gov processed this record on 2005-05-03