Effects of Vitamin D Supplementation on Depression and Inflammatory Markers

Vitamin D Deficiency Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04898725
• Other study ID #: 109-2314-B-195 -017 -MY3
• Status: Recruiting
• Phase: N/A
• Start date: April 12, 2021
• Est. completion date: June 28, 2024

Study information

• Verified date: July 2023
• Source: Mackay Memorial Hospital
• Contact: Hui-Chun Huang, PhD
• Phone: +886-2-28094661
• Email: aihch[@]mmh.org.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 460
• Est. completion date: June 28, 2024
• Est. primary completion date: April 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 24 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depression
• Vitamin D Deficiency

Intervention

Dietary Supplement:
• Vitamin D3
Vitamin D3 4800IU daily

Locations

Country	Name	City	State
Taiwan	MacKay Memorial Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Mackay Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of total score of Generalized Anxiety Disorder Questionnaire	Generalized Anxiety Disorder Questionnaire is a 7-item self-report measure, scored from 0 to 3 (range 0-21), and greater scores indicate severe anxiety symptoms.	baseline and at 8 weeks (the end of intervention)
Other	Significant change (mean±SD) in serum concentration of hs-CRP	The serum concentration of hs-CRP (mg/L) will be measured at baseline and 8 weeks after intervention. Normal range is <0.3 mg/L.	baseline and 8 weeks after intervention
Other	Significant change (mean±SD) in serum concentration of cytokine targets	The serum concentration of cytokine targets (IL-1ß, IL-2, IL-6, IL-12, IL-15, TNF-a, IFN-?, IL-4, IL-5, IL-13, IL-10, IL-1Ra) (unit: pg/mL) will be measured at baseline and 8 weeks after intervention.	baseline and 8 weeks after intervention
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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