Clinical trial NCT04898725: Effects of Vitamin D Supplementation on Depression and Inflammatory Markers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depression
Vitamin D Deficiency
Lead sponsor: Mackay Memorial Hospital
Sponsor class: OTHER
First posted: 2021-05-24
Enrollment: 142
Sex: ALL
Minimum age (years): 10
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

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

  1. including diabetes
  2. thyroid
  3. parathyroid disorder.
* 2.serious neurological disorders

  1. epilepsy
  2. severe traumatic brain injury
  3. neurodegenerative conditions
* 3.liver disease
* 4.kidney disease
* 5.heart disease
* 6.other serious health conditions.
* 7.severe mental disorders

  1. Organic mental disorders
  2. Alcohol or substance use disorders active within 3 months
  3. Schizophrenia
  4. Delusional disorder
  5. Psychotic disorders not elsewhere classified.
  6. Bipolar disorder.
  7. Autistic spectrum disorder.
  8. Anorexia nervosa.
  9. Mental retardation with IQ less than 70.
  10. High violence or suicide risk.
* 8.Patients use drugs or herbals interfering with vitamin D metabolisms

  1. phenobarbital
  2. phenytoin
  3. anti-tuberculosis drugs
  4. thiazide diuretics.
* 9.Pregnant or expect to be pregnant during study participation.

Primary outcomes:
measure: Change of total score of 17-item Hamilton Depression Rating Scale (HDRS-17)
timeFrame: baseline and at 8 weeks (the end of intervention)
Secondary outcomes:
measure: 17-item Hamilton Depression Rating Scale (HDRS-17)
timeFrame: change from baseline score at 8 weeks
measure: Response rate of 17-item Hamilton Depression Rating Scale (HDRS-17)
timeFrame: at 2 weeks, 4 weeks, 6 weeks, 8 weeks
measure: Remission rate of 17-item Hamilton Depression Rating Scale (HDRS-17)
timeFrame: at week 2, 4, 6, 8 weeks
measure: End of intervention remission rate in17-item Hamilton Depression Rating Scale (HDRS-17)
timeFrame: at 8 weeks
measure: Change of total score of Beck Depression Inventory-Second Edition
timeFrame: change from baseline score at 8 weeks
measure: Significant change (mean±SD) in vitamin D status
timeFrame: baseline and at 8 weeks
Other outcomes:
measure: Change of total score of Generalized Anxiety Disorder Questionnaire
timeFrame: baseline and at 8 weeks (the end of intervention)
measure: Significant change (mean±SD) in serum concentration of hs-CRP
timeFrame: baseline and 8 weeks after intervention
measure: Significant change (mean±SD) in serum concentration of cytokine targets
timeFrame: baseline and 8 weeks after intervention
Locations:
city: Taipei
country: Taiwan
facility: MacKay Memorial Hospital
Study officials:
affiliation: Mackay Memorial Hospital
name: Shen-Ing Liu, PhD
role: PRINCIPAL_INVESTIGATOR
References: