Vitamin D for Cognition in Bipolar Disorder

Study Overview
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Brief Summary
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Conduct randomized double-blind controlled trial (RCT), to examine the effects of vitamin D on cognitive performance in euthymic BD.

Detailed Description
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Bipolar disorder (BD) is a chronic mental disease related to recurrent episodes along with cognitive or functional decline. Comparing efficacy of pharmacological interventions targeting to treat cognitive deficit in BD is unexplored. The majority of the observational studies demonstrate a significant association between low serum vitamin D and compromised cognition in a wide range of neuropsychiatry diseases. Recent survey further revealed the high prevalence of hypovitamin D in BD. The effect of supplement and association between vitamin D and cognition in BD and the underlying mechanism is unclear. The investigators will collect vitamin D levels and assess their association with cognition in a euthymic bipolar cohort (N=200) for screen. Then, the investigators estimate to recruit 120 of participants with cognitive deficits and combined vitamin D deficiency, to conduct a RCT. Participants will keep their usual treatment and will be randomized to receive either vitamin D supplement or a placebo for eight weeks. Cognitive test, adverse side effect, mood status and blood 25(OH)D levels and biomarkers will be measured before and after intervention.

Official Title
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Effect of Vitamin D Supplement for Cognitive Function in Patients With Bipolar Disorder- Randomized Double-Blind Controlled Trial

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Dietary Supplement: solubilized vitamin D3
* Dietary Supplement: medium chain triglyceride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who diagnosed with BD-I based on the Diagnostic and Statistical Manual (DSM-IV) criteria are consecutively referred by board-certified psychiatrists in Taipei City Hospital, Songde branch. Age of participants should range from 20 to 65 years old. No history of vitamin D supplementation within three months before the study. The BD patients in their euthymic state (both Hamilton Depression Rating Scale and Young Mania Rating Scale ≤ 8) and no change of their psychoactive medications in recent three months. Exclusion Criteria: With known substance use disorder (except nicotine use disorder) With any disorder with known neurological symptoms or complications (ex. brain injury, stroke or brain lesions) Comorbid with schizophrenia spectrum disorders With active physical condition (such as renal impairment, hepatic failure…) or pregnancy Inability to complete the standard assessment or incapability of providing informed consent

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double blinded RCT
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention: solubilized vitamin D3 in MCT<br>The intervention dose and duration aims to correct their vitamin D deficiency to sufficient status (total serum 25(OH)D >/=30 ng/mL or 75 nmol/L). According to an oral cholecalciferol (D3) loading dose guideline for vitamin D-deficient adults (van Groningen et al. 2010), cumulative dose of more than 200,000 IU solubilized vitamin D3 would be applied in current RCT, with make sure the sufficient supplement. Intervention group will receive 144,000 IU in week0 (W0) and then every 2 weeks of 72,000 IU for total 8 weeks (totally 5 times: 144,000 IU wk0/ 72,000 IU wk2/ 72,000 IU wk4/ 72,000 IU wk6/ 72,000 IU wk8), theoretically to achieve sufficient levels of vitamin D. | Dietary Supplement: solubilized vitamin D3<br>* solubilized vitamin D3<br>|
| Placebo Comparator: Placebo: MCT with same amount<br>control group will receive same volume amount of medium chain triglyceride (MCT). | Dietary Supplement: medium chain triglyceride<br>* MCT with same amount<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of cognition | Change from Baseline Brief Assessment of Cognition in Affective Disorders (BAC-A) score at week 10 | Week 0, Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of serum vitamin D levels | change from baseline serum vitamin D levels to week 10, unit: ng/mL | Week 0, Week 10 | 
| change of serum creatinine | change from baseline serum creatinine to week 10, unit: mg/dL | Week 0, Week 10 | 
| change of blood albumin | change from baseline blood albumin to week 10, unit: g/dL | Week 0, Week 10 | 
| change of blood parathyroid hormone | change from baseline parathyroid hormone to week 10, unit: pg/mL | Week 0, Week 10 | 
| change of serum calcium levels | change from baseline serum calcium levels to week 10, unit: mg/dL | Week 0, Week 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar disorder, vitamin D, cognition