Effects of Vitamin D Supplementation on Depression and Inflammatory Markers

Study Overview
=================
Brief Summary
-----------------
The current study is designed as a prospective partially randomized patient preference (PRPP) trial and recruit psychiatric outpatients or inpatients. Participants who agree to receive randomization will be randomly assigned into a supplementation or placebo group, after stratification for pre-intervention vitamin D status (12-20 ng/mL or <12 ng/mL) and depression status (HDRS-17 ≥ 17 or < 17). Participants who decline randomization but agree to receive follow-up in the observational cohort choose their preferred method (either 4800 IU vitamin D3 per day, or usual care without supplementation). Severity of depression, any change of medication, and side effect will be assessed at baseline and at 2-week intervals for 8 weeks. Serum levels of 25(OH)D, C-Reactive protein (CRP) and 12 cytokines, anthropometrical measurements, dietary intake, physical activity and sun exposure will be assessed at baseline and post-intervention. Additionally, serum levels of 25(OH)D will be assessed at 4 weeks to ensure its safety level.

Detailed Description
-----------------
Investigators will conduct a partially randomized patient preference (PRPP) trial and recruit psychiatric outpatients or inpatients. Inclusion criteria are young people aged 10 to 24, fulfilling the DSM-V criteria of major depressive disorder (MDD) with scores of HDRS-17≥10, psychotropic medication have been kept unchanged for a month and will remain unchanged during intervention period, and serum 25-hydroxycholecalciferol (25-OH-D) levels lower than 20 ng/ml. Exclusion criteria are comorbid with organic mental disorders, alcohol or substance use disorders, schizophrenia, delusion disorder, bipolar disorder, autistic spectrum disorder, anorexia nervosa, and IQ less than 70; endocrine disorders including diabetes, thyroid and parathyroid disorder; serious neurological disorders including epilepsy, severe traumatic brain injury, and neurodegenerative conditions; liver disease, kidney disease, heart disease or other serious health conditions; use drug interfering with vitamin D metabolism. Participants who agree to receive randomization will be randomly assigned into a supplementation or placebo group, after stratification for pre-intervention vitamin D status (12-20 ng/mL or <12 ng/mL) and depression status (HDRS-17 ≥ 17 or < 17). Supplementation arm will receive oral dose 4800 IU vitamin D3 per day (three soft capsules of 800 IU vitamin D, twice a day) and placebo arm will receive placebo every day (three soft capsules with identical appearance, twice a day) for 8 weeks. Both groups continue to receive standard psychiatric care by child psychiatrists. Randomization and allocation will be concealed from researchers, participants and treating physicians. Participants who decline randomization but agree to receive follow-up in the observational cohort choose their preferred method (either 4800 IU vitamin D3 per day, or usual care without supplementation). Severity of depression, any change of medication, and side effect will be assessed at baseline and at 2-week intervals for 8 weeks. Serum levels of 25(OH)D, CRP and 12 cytokines, anthropometrical measurements, dietary intake, physical activity and sun exposure will be assessed at baseline and post-intervention. Additionally, serum levels of 25(OH)D will be assessed at 4 weeks to ensure its safety level.

Official Title
-----------------
Effects of Vitamin D Supplementation on Depression and Inflammatory Markers in Adolescent and Youth With Major Depression and Vitamin D-deficiency: a Partially Randomized Preference Trial in Taiwan

Conditions
-----------------
Major Depression, Vitamin D Deficiency

Intervention / Treatment
-----------------
* Dietary Supplement: Vitamin D3


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1.patients who attend psychiatric outpatient clinics or who are admitted to the psychiatric inpatient ward at the above sites. 2.clinical diagnosis of depression-related disorders and scores of HDRS-17 ≥ 10. 3.psychotropics have been kept unchanged for at least a month. 4.aged 10 to 24. 5.serum 25-hydroxycholecalciferol (25-OH-D) levels lower than 20 ng/ml. Exclusion Criteria: 1.endocrine disorders including diabetes thyroid parathyroid disorder. 2.serious neurological disorders epilepsy severe traumatic brain injury neurodegenerative conditions 3.liver disease 4.kidney disease 5.heart disease 6.other serious health conditions. 7.severe mental disorders Organic mental disorders Alcohol or substance use disorders active within 3 months Schizophrenia Delusional disorder Psychotic disorders not elsewhere classified. Bipolar disorder. Autistic spectrum disorder. Anorexia nervosa. Mental retardation with IQ less than 70. High violence or suicide risk. 8.Patients use drugs or herbals interfering with vitamin D metabolisms phenobarbital phenytoin anti-tuberculosis drugs thiazide diuretics. 9.Pregnant or expect to be pregnant during study participation.

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 24 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vit D Group (randomized)<br>Subjects will be randomly assigned to receive a daily vitamin D supplementation (4800IU daily) for 8 weeks | Dietary Supplement: Vitamin D3<br>* Vitamin D3 4800IU daily<br>|
| No Intervention: Control Group (randomized)<br>Subjects will be randomly assigned to receive a placebo for 8 weeks. | |
| Experimental: Preference Vit D Group (non-randomized)<br>Subjects with a strong preference to receive a daily vitamin D supplementation (4800IU daily) for 8 weeks. | Dietary Supplement: Vitamin D3<br>* Vitamin D3 4800IU daily<br>|
| No Intervention: Preference no Vit D Group (non-randomized)<br>Subjects with a strong preference to receive usual care (not receiving vitamin D supplements) for 8 weeks. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of total score of 17-item Hamilton Depression Rating Scale (HDRS-17) | 17-item Hamilton Depression Rating Scale is an interview-based instrument for rating the overall levels of severity of the symptoms of depression and the response to treatment. Each item is rated from 0 to 4 or 0 to 2; the scores correspond to increases in severity. Total scores range from 0 to 52. | baseline and at 8 weeks (the end of intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 17-item Hamilton Depression Rating Scale (HDRS-17) | HDRS-17 is measured totally 5 times, at week 0, 2 weeks, 4 weeks, 6 weeks, 8 weeks. The change in total HDRS-17 score between baseline and the intermediate 2-week, 4-week, 6-week follow-ups were considered secondary outcomes measures. | change from baseline score at 8 weeks | 
| Response rate of 17-item Hamilton Depression Rating Scale (HDRS-17) | Response rate is defined as a reduction in HDRS-17 total score of at least 50 percent relative to the beginning of the randomized phase (baseline). | at 2 weeks, 4 weeks, 6 weeks, 8 weeks | 
| Remission rate of 17-item Hamilton Depression Rating Scale (HDRS-17) | Remission rate is defined as an absolute HDRS-17 total score of ≤ 7 at each follow-up assessment. | at week 2, 4, 6, 8 weeks | 
| End of intervention remission rate in17-item Hamilton Depression Rating Scale (HDRS-17) | Remission rate is defined as an absolute HDRS-17 total score of ≤ 7 at the end of treatment (8 week after intervention). | at 8 weeks | 
| Change of total score of Beck Depression Inventory-Second Edition | Beck Depression Inventory is a 21-item self-report measure, scored from 0 to 3 (range 0-63), and greater scores indicate severe depression symptoms.Beck Depression Inventory (BDI) is measured totally 5 times, at week 0, 2 weeks, 4 weeks, 6 weeks, 8 weeks. The change in total BDI score between baseline and each of follow-ups (2-week, 4-week, 6-week, 8-week follow-ups) were considered secondary outcomes measures. | change from baseline score at 8 weeks | 
| Significant change (mean±SD) in vitamin D status | serum levels of 25(OH)D, units of measure is ng/mL | baseline and at 8 weeks |