Depression, Diabetes, Quality of Life
Conditions
Keywords
Vitamin D, Diabetes, Self-Management, Depression, Women
Brief summary
This is a randomized clinical trial (RCT) to determine the effectiveness of vitamin D3 supplementation on depressive symptoms, self-management, and blood pressure in approximately 180 adult women with type 2 diabetes who have significant depressive symptoms. Consenting adult women who are eligible to participate will be randomly assigned to either a weekly dose of 50,000 international units of vitamin D3 supplementation or a matching weekly active comparator of 5,000 international units of vitamin D3 for six months. Participants will complete approximately four in-person study visits and several telephone visits throughout the six month trial period, where the researchers will assess depressive symptoms, diabetes self-management, and systolic blood pressure.
Detailed description
The primary aim of this study is to determine the effect of vitamin D supplementation on depressive symptoms, self-management, and systolic blood pressure compared to placebo. The hypothesis is that women receiving vitamin D supplementation will report fewer depressive symptoms, increased diabetes self- management mediated by depression improvement, and will have a lower systolic blood pressure compared to those taking placebo at three and six months follow-up. The secondary aim is to explore the mechanistic effect of vitamin D supplementation on inflammatory biomarkers and their association with depression. Here, the hypothesis is that women receiving vitamin D supplementation will have a decrease in inflammatory biomarkers which will be associated with fewer depressive symptoms compared to those taking placebo at three and six months follow-up.
Interventions
DRUGVitamin D3
50,000 international units (IUs) weekly Vitamin D3
DRUGVitamin D3 comparator
5,000 international units (IUs) of a weekly Vitamin D3 comparator
Sponsors
National Institutes of Health (NIH)
National Institute of Nursing Research (NINR)
Loyola University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants are randomized to either 50,000 international units of weekly vitamin D3 or to 5,000 international units of weekly vitamin D3 using a 1:1 allocation
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women age 21 and older * Objective evidence of depressive symptoms at the screening and baseline visits * Diagnosis of type 2 diabetes currently being treated by a healthcare provider * Blood vitamin D level less than 32 nanograms-per-deciliter (32 ng/dl)
Exclusion criteria
* Current alcohol or substance use disorder * Any unstable or severe psychiatric disease including diagnoses of schizophrenia, bipolar affective disorder, dementia, delirium, or other psychotic disorder * Severe complications of diabetes, such as blindness and/or amputation * Any malabsorption disorder, such as Crohn's disease and/or celiac sprue * Elevated serum calcium level deemed significant by the Principal Investigator * Use of 1,000 or more international units daily vitamin D 60 days before enrollment and unwillingness to discontinue vitamin D supplementation 30 days before enrollment. * Use of St. John's Wort and unwillingness to discontinue St. John's Wort three weeks prior to enrollment. * Participants who are pregnant, nursing, or planning to become pregnant during the study. * Baseline systolic blood pressure (SBP) greater than 160 millimeters of mercury (mmHG) or diastolic blood pressure (DBP) greater than 100 mmHG. * Other serious medical conditions (e.g., cancer, multiple sclerosis, etc.) deemed clinically significant by the Principal Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Center for Epidemiologic Studies Depression (CES-D) Score From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | Baseline and 6 months | The Center for Epidemiologic Studies Depression (CES-D) is a self-report questionnaire assessing frequency and severity of depression symptoms. Raw scores range from 0 to 60, where higher scores indicate worse mood. For each participant, her baseline CES-D score is subtracted from her month 6 CES-D score to create a CES-D change score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Problem Areas in Diabetes (PAIDS) Score From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | Baseline and 6 months | The Problem Areas in Diabetes (PAIDS) score is a self-report questionnaire that assesses diabetes burden and treatment. Scores range from 0 to 100, where higher scores indicate greater distress. For each participant, her baseline PAID score is subtracted from her month 6 PAID score to create a PAID change score. |
| Change in Systolic Blood Pressure From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | Baseline and 6 months | Systolic blood pressure is measured in millimeters of mercury (mmHg). For each participant, her baseline systolic blood pressure is subtracted from her month 6 systolic blood pressure to create a systolic blood pressure change score. |
| Change in Diastolic Blood Pressure From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | Baseline and 6 months | Diastolic blood pressure is measured in millimeters of mercury (mmHg). For each participant, her baseline diastolic blood pressure is subtracted from her month 6 diastolic blood pressure to create a diastolic blood pressure change score. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from November 2013 through November 2017 (48 months)
Pre-assignment details
Two-hundred sixty-five participants consented to participate in the study. Among these individuals, 136 (51.3%) were not randomized for failing to meet study inclusion criteria (134/136 or 98.5%) or because they withdrew consent prior to randomization (2/136 or 1.5%).
Participants by arm
| Arm | Count |
|---|---|
| Low Dose 5,000 international units (IUs) of a weekly Vitamin D3 comparator | 64 |
| High Dose 50,000 international units (IUs) weekly Vitamin D3 | 65 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lost to Follow-up | 4 | 2 |
Baseline characteristics
| Characteristic | Low Dose | High Dose | Total |
|---|---|---|---|
| Age, Continuous | 51.14 years STANDARD_DEVIATION 9.4 | 50.02 years STANDARD_DEVIATION 12.65 | 50.58 years STANDARD_DEVIATION 11.13 |
| Annual Household Income $10,000 to $14,999 | 9 Participants | 4 Participants | 13 Participants |
| Annual Household Income $15,000 to $19,999 | 1 Participants | 5 Participants | 6 Participants |
| Annual Household Income $20,000 to $29,999 | 5 Participants | 9 Participants | 14 Participants |
| Annual Household Income $30,000 to $39,999 | 8 Participants | 5 Participants | 13 Participants |
| Annual Household Income $40,000 to $49,999 | 5 Participants | 9 Participants | 14 Participants |
| Annual Household Income $50,000 to $59,999 | 6 Participants | 6 Participants | 12 Participants |
| Annual Household Income $5,000 to $9,999 | 4 Participants | 4 Participants | 8 Participants |
| Annual Household Income $60,000 to $69,999 | 4 Participants | 4 Participants | 8 Participants |
| Annual Household Income $70,000 or more | 17 Participants | 12 Participants | 29 Participants |
| Annual Household Income Less than $5,000 | 5 Participants | 7 Participants | 12 Participants |
| Body mass index | 39.10 kg/m^2 STANDARD_DEVIATION 8.28 | 37.65 kg/m^2 STANDARD_DEVIATION 7.71 | 38.37 kg/m^2 STANDARD_DEVIATION 8 |
| Calcium | 9.4 mg/dL | 9.4 mg/dL | 9.4 mg/dL |
| CES-D | 28.41 units on a scale STANDARD_DEVIATION 8.39 | 28.72 units on a scale STANDARD_DEVIATION 8.5 | 28.57 units on a scale STANDARD_DEVIATION 8.41 |
| Creatinine | 0.74 mg/dL STANDARD_DEVIATION 0.14 | 0.75 mg/dL STANDARD_DEVIATION 0.15 | 0.75 mg/dL STANDARD_DEVIATION 0.14 |
| Diastolic blood pressure | 71.97 mmHg STANDARD_DEVIATION 10.64 | 70.94 mmHg STANDARD_DEVIATION 8.75 | 71.45 mmHg STANDARD_DEVIATION 9.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 12 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 53 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting glucose | 170.47 mg/dL STANDARD_DEVIATION 68.63 | 152.52 mg/dL STANDARD_DEVIATION 48.76 | 161.43 mg/dL STANDARD_DEVIATION 59.9 |
| HBA1C | 7.86 percentage of hemoglobin STANDARD_DEVIATION 1.97 | 7.68 percentage of hemoglobin STANDARD_DEVIATION 1.69 | 7.77 percentage of hemoglobin STANDARD_DEVIATION 1.83 |
| Highest level of education 8th grade or less | 0 Participants | 1 Participants | 1 Participants |
| Highest level of education College graduate (bachelor's degree) | 16 Participants | 17 Participants | 33 Participants |
| Highest level of education Graduate degree | 9 Participants | 11 Participants | 20 Participants |
| Highest level of education High school graduate or GED | 10 Participants | 8 Participants | 18 Participants |
| Highest level of education Some college or technical school | 24 Participants | 26 Participants | 50 Participants |
| Highest level of education Some high school | 5 Participants | 2 Participants | 7 Participants |
| Parathyroid Hormone | 49 ng/L | 49 ng/L | 49 ng/L |
| PHQ-9 | 11.91 units on a scale STANDARD_DEVIATION 4.2 | 11.74 units on a scale STANDARD_DEVIATION 4.29 | 11.82 units on a scale STANDARD_DEVIATION 4.23 |
| Race/Ethnicity, Customized Race Arabic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian or Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black | 28 Participants | 34 Participants | 62 Participants |
| Race/Ethnicity, Customized Race Not reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 34 Participants | 29 Participants | 63 Participants |
| Region of Enrollment United States | 64 participants | 65 participants | 129 participants |
| Sex: Female, Male Female | 64 Participants | 65 Participants | 129 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Systolic blood pressure | 128.41 mmHg STANDARD_DEVIATION 16.4 | 127.43 mmHg STANDARD_DEVIATION 14.96 | 127.91 mmHg STANDARD_DEVIATION 15.63 |
| Use of anti-depressants No | 53 Participants | 52 Participants | 105 Participants |
| Use of anti-depressants Not reported | 0 Participants | 1 Participants | 1 Participants |
| Use of anti-depressants Yes | 11 Participants | 12 Participants | 23 Participants |
| Vitamin D3 Level | 18.61 ng/mL STANDARD_DEVIATION 6.66 | 20.63 ng/mL STANDARD_DEVIATION 6.6 | 19.63 ng/mL STANDARD_DEVIATION 6.68 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 65 |
| other Total, other adverse events | 55 / 64 | 60 / 65 |
| serious Total, serious adverse events | 5 / 64 | 7 / 65 |
Outcome results
Primary
Change in Center for Epidemiologic Studies Depression (CES-D) Score From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort
The Center for Epidemiologic Studies Depression (CES-D) is a self-report questionnaire assessing frequency and severity of depression symptoms. Raw scores range from 0 to 60, where higher scores indicate worse mood. For each participant, her baseline CES-D score is subtracted from her month 6 CES-D score to create a CES-D change score.
Time frame: Baseline and 6 months
Population: The analysis population includes all women randomized to low dose or high dose therapy and completed the month 6 CES-D assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change in Center for Epidemiologic Studies Depression (CES-D) Score From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | -13.2982 units on a scale | Standard Deviation 10.2312 |
| High Dose | Change in Center for Epidemiologic Studies Depression (CES-D) Score From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | -12.5000 units on a scale | Standard Deviation 12.0065 |
Comparison: The null hypothesis is that there is no difference in the CES-D change score between women who received high dose Vitamin D therapy versus low dose Vitamin D therapy.p-value: 0.698295% CI: [-3.2691, 4.8656]t-test, 2 sided
Secondary
Change in Diastolic Blood Pressure From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort
Diastolic blood pressure is measured in millimeters of mercury (mmHg). For each participant, her baseline diastolic blood pressure is subtracted from her month 6 diastolic blood pressure to create a diastolic blood pressure change score.
Time frame: Baseline and 6 months
Population: The analysis population includes all women randomized to low dose or high dose therapy and completed the in-person month 6 study visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change in Diastolic Blood Pressure From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | -0.7544 mmHg | Standard Deviation 10.6692 |
| High Dose | Change in Diastolic Blood Pressure From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | 0.7581 mmHg | Standard Deviation 9.6609 |
Comparison: The null hypothesis is that there is no difference in the change in diastolic blood pressure between women who received high dose Vitamin D therapy versus low dose Vitamin D therapy.p-value: 0.418795% CI: [-2.1784, 5.2033]t-test, 2 sided
Secondary
Change in Problem Areas in Diabetes (PAIDS) Score From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort
The Problem Areas in Diabetes (PAIDS) score is a self-report questionnaire that assesses diabetes burden and treatment. Scores range from 0 to 100, where higher scores indicate greater distress. For each participant, her baseline PAID score is subtracted from her month 6 PAID score to create a PAID change score.
Time frame: Baseline and 6 months
Population: The analysis population includes all women randomized to low dose or high dose therapy and completed the month 6 PAID assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change in Problem Areas in Diabetes (PAIDS) Score From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | -13.2237 score on a scale | Standard Deviation 17.6238 |
| High Dose | Change in Problem Areas in Diabetes (PAIDS) Score From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | -13.2661 score on a scale | Standard Deviation 21.8782 |
Comparison: The null hypothesis is that there is no difference in the PAID change score between women who received high dose Vitamin D therapy versus low dose Vitamin D therapy.p-value: 0.990895% CI: [-7.2946, 7.2097]t-test, 2 sided
Secondary
Change in Systolic Blood Pressure From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort
Systolic blood pressure is measured in millimeters of mercury (mmHg). For each participant, her baseline systolic blood pressure is subtracted from her month 6 systolic blood pressure to create a systolic blood pressure change score.
Time frame: Baseline and 6 months
Population: The analysis population includes all women randomized to low dose or high dose therapy and completed the in-person month 6 study visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change in Systolic Blood Pressure From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | -2.1579 mmHg | Standard Deviation 17.6491 |
| High Dose | Change in Systolic Blood Pressure From Baseline (Month 0) to Month 6 for the High Dose Cohort Versus Low Dose Cohort | -1.6613 mmHg | Standard Deviation 16.6821 |
Comparison: The null hypothesis is that there is no difference in the change in systolic blood pressure between women who received high dose Vitamin D therapy versus low dose Vitamin D therapy.p-value: 0.874995% CI: [-5.7366, 6.7298]t-test, 2 sided