Clinical Trial of a Nutritional Supplement in Adults With Bipolar Disorder

• Sponsor: University of Calgary (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00109577
• Collaborator: Alberta Innovation and Science (Other)
• Enrollment: 40
• Locations: 2
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 20
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: MCN36 (nutritional supplement); Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Placebo-controlled Phase II Trial of MCN36 in Adults With Bipolar Disorder
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 2 Placebo comparator, 6 placebo capsules three times a day	Drug: Placebo; nutritional supplement
Experimental: 1 nutritional supplement intervention, 6 nutritional supplement capsules three times a day; the nutritional supplement is a 36-ingredient micronutrient supplement (primarily vitamins and minerals) and is referred to as MCN36, because it contains 36 nutrients.	Drug: MCN36 (nutritional supplement); nutritional supplement

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Global Clinical Impressions [Baseline to 8 weeks]

2. Outcome Questionnaire --- a Self-report Questionnaire [Baseline to 8 weeks]

3. Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) [Baseline to 8 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dr Estelle Goldstein	San Diego	California	United States	92116
2	University of Calgary Faculty of Medicine	Calgary	Alberta	Canada	T2N 4N1

Sponsors and Collaborators

• University of Calgary
• Alberta Innovation and Science

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Kaplan BJ, Crawford SG, Field CJ, Simpson JS. Vitamins, minerals, and mood. Psychol Bull. 2007 Sep;133(5):747-60. Review.
• Kaplan BJ, Crawford SG, Gardner B, Farrelly G. Treatment of mood lability and explosive rage with minerals and vitamins: two case studies in children. J Child Adolesc Psychopharmacol. 2002 Fall;12(3):205-19.
• Kaplan BJ, Fisher JE, Crawford SG, Field CJ, Kolb B. Improved mood and behavior during treatment with a mineral-vitamin supplement: an open-label case series of children. J Child Adolesc Psychopharmacol. 2004 Spring;14(1):115-22.
• Kaplan BJ, Simpson JS, Ferre RC, Gorman CP, McMullen DM, Crawford SG. Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder. J Clin Psychiatry. 2001 Dec;62(12):936-44.
• Popper CW. Do vitamins or minerals (apart from lithium) have mood-stabilizing effects? J Clin Psychiatry. 2001 Dec;62(12):933-5.
• Simmons M. Nutritional approach to bipolar disorder. J Clin Psychiatry. 2003 Mar;64(3):338; author reply 338-9.

• Responsible Party: Bonnie Kaplan, Professor, University of Calgary
• ClinicalTrials.gov Identifier: NCT00109577
• Other Study ID Numbers: 18229; AIS99-03A (01406-005-23)
• First Posted: Apr 29, 2005
• Last Update Posted: Sep 18, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Bonnie Kaplan, Professor, University of Calgary: bipolar disorder; mood disorders; manic depression; nutrition
• Additional relevant MeSH terms: Disease; Bipolar Disorder

Study Results

Participant Flow

Arm/Group Title	Placebo Comparator	Micronutrient Formula
Arm/Group Description	Placebo comparator capsules	nutritional supplement capsules containing 36-ingredients primarily vitamins and minerals; the supplement is referred to as MCN36, because it contains 36 nutrients.
Period Title: Overall Study
STARTED	20	20
COMPLETED	17	17
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Placebo Comparator	Micronutrient Formula	Total
Arm/Group Description	Placebo comparator	nutritional supplement	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40 (13)	35 (9)	37.5 (11)
Sex: Female, Male (Count of Participants)
Female	12 60%	11 55%	23 57.5%
Male	8 40%	9 45%	17 42.5%
Region of Enrollment (participants) [Number]
United States	4 20%	3 15%	7 17.5%
Canada	16 80%	17 85%	33 82.5%

Outcome Measures

1. Primary Outcome

Title	Mood as Evaluated by the Overall Bipolarity Index (Composite of the Hamilton Depression Scale and the Young Mania Rating Scale)
Description	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

Outcome Measure Data

Analysis Population Description

All participants were included, since the analysis was intent-to-treat with last observation carried forward

Arm/Group Title	Placebo Comparator	Micronutrient Formula
Arm/Group Description	Placebo comparator capsules	nutritional supplement capsules
Measure Participants	20	20
Mean (Standard Deviation) [units on a scale]	-21.1 (3.4)	-18.9 (2.9)

2. Secondary Outcome

Title	Global Clinical Impressions
Time Frame	Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Outcome Questionnaire --- a Self-report Questionnaire
Time Frame	Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)
Time Frame	Baseline to 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Placebo Comparator		Micronutrient Formula
Arm/Group Description	Placebo comparator		nutritional supplement
All Cause Mortality
	Placebo Comparator		Micronutrient Formula
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Comparator		Micronutrient Formula
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Comparator		Micronutrient Formula
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.