Vitamin D supplements to prevent depression and poor physical function in persons over 60 years.

Background of the study:

Depressive symptoms are common in older persons, often associated with poor physical function and vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nmol/l). Simple and cheap interventions to prevent depression are lacking. Vitamin D deficiency occurs in 50% of persons >65 yr and has been associated with an increase in depressive symptoms in many studies, as well as with functional limitations and declining physical performance. A prior randomized placebo-controlled trial on the effect of vitamin D supplementation in overweight persons showed a decrease in depressive symptoms. Vitamin D supplementation also had a positive influence on mobility tests in several clinical trials. A mechanistic explanation is available: the vitamin D receptor is present in muscle cells as well as in brain tissue, especially in the hypothalamus. The hypothesis is that vitamin D decreases depressive symptoms and improves physical performance and functional limitations in older persons. Secondary hypotheses are that vitamin D decreases anxiety, improves cognitive functioning and quality of life, and prevents the development of full-blown depression in older persons.



Objective of the study:

Primary objectives:

1. Does vitamin D supplementation improve depressive symptoms in older persons?

2. Does vitamin D supplementation improve physical performance and functional limitations in older persons?



Secondary objectives:

1. Does vitamin D supplementation decrease anxiety and improve cognitive function and quality of life in older persons?

2. Can vitamin D supplementation prevent the development of full-blown depression in older persons?

3. Is vitamin D supplementation a cost-effective strategy in the prevention of increasing depressive symptoms and functional limitations and declining physical performance?



Study design:

A randomized double-blind placebo-controlled intervention study on the effect of vitamin D 1200 IU per day versus placebo on depressive symptoms, physical performance and functional limitations. The duration of intervention and follow-up is one year.



Study population:

Potential participants are recruited in The Netherlands, aged 60 to 80 years, are recruited in general practices with the Center of Epidemiological Studies Depression Scale (CES-D). They are eligible when having mild depressive symptoms, i.e. a CES-D score of 16 or higher. Further inclusion criteria are the presence of at least one functional limitation and a serum 25-hydroxyvitamine D concentration between 15 nmol/l and 50 nmol/l in winter or 70 nmol/l in summer. Patients with a diagnosis of depression are excluded. According to the sample size calculation and drop out, 50 persons per group, i.e.100 persons are required. Because of uncertainty in the 25-hydroxyvitamin D assay during screening, 70 persons per group will be included, altogether 140 persons..



Intervention:

The patients are randomized into two groups: vitamin D 1200 IU (three tablets of 400 IU per day) or placebo (three tablets per day) for one year.



Primary study parameters/outcome of the study:

Change in the CES-D score, change in physical performance score after 12 months, change in the number of functional limitations as well as change of degree of functional limitations.



Secundary study parameters/outcome of the study:

Change in anxiety, cognition, quality of life, incidence of full-blown depression, timed up-and-go-test, costs.



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Potential participants are screened with postal questionnaires and a screening visit to their general practice (short questionnaire and blood sample). After screening, they have to come 3 times to the general practice or health center at baseline, after 6 and 12 months. They have to complete questionnaires, perform physical performance tests, and a blood sample is drawn twice at baseline and 6 months. Assessments at 3 weeks, 3 months and 9 months are by telephone. The risk of the vitamin D treatment is negligible.

Depressive symptoms are common in older persons, often associated with poor physical function and vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nmol/l). Simple and cheap interventions to prevent depression are lacking. Vitamin D deficiency occurs in 50% of persons >65 yr and has been associated with an increase in depressive symptoms in many studies, as well as with functional limitations and declining physical performance. A prior randomized placebo-controlled trial on the effect of vitamin D supplementation in overweight persons showed a decrease in depressive symptoms. Vitamin D supplementation also had a positive influence on mobility tests in several clinical trials. A mechanistic explanation is available: the vitamin D receptor is present in muscle cells as well as in brain tissue, especially in the hypothalamus. The hypothesis is that vitamin D decreases depressive symptoms and improves physical performance and functional limitations in older persons. Secondary hypotheses are that vitamin D decreases anxiety, improves quality of life and prevents the development of full-blown depression in older persons.

Primary outcomes:

1. Change in depressive symptoms (CES-D score) after 12 months;

2. Change in physical performance score after 12 months;

3. Change in number and degree of functional limitations after 12 months.



Secondary outcomes:

1. Change in depressive symptoms (CES-D score), after 6 months;

2. Change in physical performance score after 6 months;

3. Change in number and degree of functional limitations after 6 months;

4. Number of subjects with a full-blown major depressive disorder (CIDI score) after 6 and 12 months;

5. Change in anxiety (Beck Anxiety Index score) after 6 and 12 months;

6. Change in cognition (Stroop Colour-Word Test score) after 6 and 12 months;

7. Change in quality of life (EQ-5D and SF-36 score) after 6 and 12 months.

Experimental group: 1200 IU of vitamin D per day, in 3 tablets of 400 IU, for 12 months. Active substance: Colecalciferol. Product name: Devaron.



Placebo group: 3 placebo tablets per day for 12 months. (similar to Devaron tablets in size, shape, taste etc., but no active substance).