Clinical trial NCT03541031: Micronutrients as Adjunctive Treatment for Bipolar Disorder
Official title: Micronutrients as Adjunctive Treatment for Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Bipolar Disorder
Lead sponsor: Eastern Maine Medical Center
Sponsor class: OTHER
First posted: 2018-05-30
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a double-blind, randomized clinical trial that will assign 120 stable adult outpatients with bipolar disorder, type I or II (DSM-V criteria) to supplementation with a 36-ingredient vitamin/mineral mix (Micronutrient) and an omega-3 fatty acid supplement (Fish oil) (N=72) or to matched double placebo (N=48) in a 3:2 ratio for a year.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of the trial is to determine whether a 36-ingredient Micronutrient supplement (primarily vitamins and minerals) and Fish oil (omega-3 fatty acid) supplement improves nutritional status and allows lower doses of conventional medications to be effective for bipolar disorder with fewer side effects, when studied under randomized and fully blinded conditions and compared to a placebo. All participants must live in the vicinity of Bangor, Maine.

Detailed description: Bipolar disorder is a common neuropsychiatric illness with high rates of morbidity and mortality. Despite available medications to treat bipolar disorder, recurrence rates are high. Bipolar disorder is conventionally treated with typical or antipsychotic medications are well described and include the increased risk of acute kidney injury, cataracts, decreased cognitive function, increased risk for myocardial infarction and stroke, metabolic syndrome and type 2 diabetes mellitus, and dyslipidemia. Related to this, mortality rates are elevated among people with bipolar disorder compared to the general population. Men with the diagnosis of bipolar disorder live, on average 13.6 years less than the general population, and for women, 12.1 years less.

This RCT (randomized clinical trial) compares a 36-ingredient Micronutrient supplement and Fish oil supplement to matched double placebo in patients randomized to receive one or the other for 52 weeks. One hundred twenty (120) patients are randomized in a 3:2 ratio to Micronutrient + Fish oil or to placebo, respectively. All patients are stably medicated adult outpatients with bipolar disorder (type I or type II). Medical supervision is provided with monthly appointments. At the end of the 52 weeks, all participants will be offered the opportunity of entering a 52-week open-label extension. The primary hypothesis is that active supplementation will allow significantly more reduction of conventional medication than placebo will, without a significant increase in symptoms and with significantly fewer side effects/adverse events.

The objective of this study is to assess the efficacy of Micronutrient supplement + Fish oil compared with placebo in stably medicated adults with bipolar disorder I and II, in improving nutritional status, allowing conventional medication to be effective at lower doses and with fewer side effects at the end of 52 weeks of therapy as assessed under randomized and fully blinded conditions. The primary outcome measure is a composite z-score for side effects, calculated from three separate z-scores that measure medication dosage, illness intensity (Clinical Global Impression score), and adverse side effects (UKU Side Effect score). Secondary outcomes include

* Symptom severity using the Positive and Negative Symptom Scale (PANSS)
* Mania symptoms using the Young Mania Rating Scale (YMRS)
* Anxiety symptoms using the Hamilton Anxiety scale (Ham-A)
* Depression symptoms using the Montgomery-Asberg Depression Rating Scale (MADRS)
* Quality of life, patient-reported using My Medical Outcome Profile version 2 (MYMOP-2)
* Nutritional status using the Mini Nutritional Assessment scale (MNA)
* Functionality, patient-reported using the 24-item Behavior and Symptom Identification Scale (BASIS-24)
* Vital signs (waist circumference, body mass index, blood pressure, heart rate, and respirations)

Treatment-emergent adverse events are documented at each appointment using the Adverse Event Log. Participants are screened and their suitability for the trial confirmed at the first visit. If suitability is confirmed, informed consent is obtained and they enter the randomized phase. Participants are seen monthly for 12 months, at which time (1) their medication is optimized (graded reduction in dose by 10% per month, upwards if symptoms are above the acceptable level and downwards if an acceptable level of symptom relief has been achieved); (2) symptoms and side effects are recorded; and (3) questionnaires are administered.

Eligibility criteria: Inclusion Criteria:

Individuals enrolled will be adult outpatients with a diagnosis of bipolar disorder I or II, receiving care at the Family Medicine Center \& Residency Program of Eastern Maine Medical Center in Bangor, Maine. Participants must be able to complete questionnaires and examinations and comply with protocols.

Exclusion Criteria:

Participants will be excluded from the study for any of the following reasons:

1. Evidence of untreated or unstable thyroid disease (until it is treated and stabilized).
2. Known abnormality of mineral metabolism (e.g., Wilson's disease) until stabilized.
3. Unable to speak English
4. Any hypervitaminosis syndrome
5. Acute suicidality (until stabilized).

Participation in the study will not alter the participants' clinical care except that they will be provided Micronutrients and Fish oil (or placebos for each) and will participate in a monthly evaluation of the effect of adding these Micronutrients. We will ask them what other supplements they are taking and will instruct them not to take supplements that contain any of the same ingredients that they will receive in the study so as to avoid exceeding the maximum dose allowed.

Primary outcomes:
measure: Changes in Side Effects
timeFrame: Baseline and every month for 1 year
Secondary outcomes:
measure: Changes in Symptom Severity
timeFrame: Baseline and every 3 months for 1 year
measure: Changes in Mania Symptoms
timeFrame: Baseline and every 3 months for 1 year
measure: Changes in Anxiety Symptoms
timeFrame: Baseline and every 3 months for 1 year
measure: Changes in Depression
timeFrame: Baseline and every 3 months for 1 year
measure: Changes in Quality of Life (patient-reported)
timeFrame: Baseline and every month for 1 year
measure: Changes in Nutritional Status
timeFrame: Baseline and every 4 months for 1 year
measure: Changes in Functionality (patient-reported)
timeFrame: Baseline and every 3 months for 1 year
measure: Changes in Waist Circumference
timeFrame: Baseline and every 4 months for 1 year
measure: Changes in Basal Metabolic Index
timeFrame: Baseline and every 4 months for 1 year
measure: Changes in Blood Pressure
timeFrame: Baseline and every 4 months for 1 year
measure: Changes in Heart Rate
timeFrame: Baseline and every 4 months for 1 year
measure: Changes in Respirations
timeFrame: Baseline and every 4 months for 1 year
Other outcomes:
Locations:
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
Study officials:
affiliation: Eastern Maine Medical Center
name: Lewis Mehl-Madrona, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: