Depression, Insulin Resistance, PCOS, Vitamin D Deficiency
Conditions
Keywords
PCOS, Depression, Vitamin D, Insulin Resistance, Anxiety, Quality of life, Mood disorders
Brief summary
Open-label randomized clinical trial assessing the efficacy of Metformin versus Vitamin D in improving symptoms of depressed mood in polycystic ovary syndrome.
Detailed description
This is a single center, open-label, randomized, pilot clinical trial. Women with polycystic ovary syndrome and depressed mood, who are insulin resistant and vitamin D insufficient are eligible. Subjects are randomly assigned to one of two interventions: Vitamin D versus metformin. Subjects are followed with questionnaires and a final wrap-up clinic visit with a physician. The study duration is 12 weeks.
Interventions
DRUGMetformin
Oral medication daily
DRUGVitamin D
Oral medication daily
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Polycystic Ovary Syndrome diagnosis (Rotterdam Criteria) * Vitamin D insufficiency (serum Vitamin D \<30 ng/mL) * Insulin resistance * Mild or greater severity of depression by Beck Depression Inventory-II
Exclusion criteria
* Current metformin use * Vitamin D supplementation of \> 50,000 IU following confirmation of Vitamin D insufficiency * Insulin-dependent diabetes mellitus * Pregnancy or breastfeeding * Untreated hypothyroidism * Current active substance abuse * Other major medical comorbidity: renal or hepatic dysfunction, severe pulmonary * Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Depression Score on the Beck Depression Inventory (BDI-II) at 12 Weeks | Baseline & 12 weeks | BDI-II is a validated self-reported instrument of 21 questions which are each scored 0-3. Total scores range from 0-63, with higher score totals indicating more severe depression symptoms. {0-9: indicates minimal depression; 0-18: indicates mild depression; 19-29: indicates moderate depression; 30-63: indicates severe depression}. Change = Week 12 total score - Baseline week score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline Week in Insulin Resistance Score at Week 12. | Baseline week & week 12 | Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) will be used to calculate Insulin Resistance based on fasting glucose (mg/dL) and fasting insulin (μIU/mL) blood serum assays tested at Quest Diagnostics. HOMA-IR = Fasting Insulin (uIU/mL) x Fasting Glucose (mg/dL). Healthy range is between 0.5-1.4. Values below 1.0 indicate insulin sensitivity and are optimal. Values greater than 1.9 indicate clinically significant insulin resistance. |
| Change From Baseline in State-Trait Anxiety Inventory Score (STAI-S) at 12 Weeks | Baseline week & Week 12 | STAI-S is a validated self-reported instrument of 20 questions. Range of scores for the State Anxiety (STAI-S) subtest is 20-80, the higher score indicating greater anxiety. A threshold point score of 39-40 has been suggested by recent literature to detect clinically significant symptoms. Change = Week 12 total score - Baseline week score |
| Changes From Baseline Week in Vitamin D 25-hydroxy Levels at Week 12. | Baseline week & week 12 | Vitamin D, 25-hydroxy blood serum assays will be tested at Quest Diagnostics. Changes in values from baseline week to week 12 will be calculated. Reference ranges: optimal 30-100 ng/mL Insufficient 20-29 ng/mL deficient \<20ng/mL |
Countries
United States
Participant flow
Pre-assignment details
Of the 5 participants that were enrolled in the trial, all were randomized and assigned to treatment arms. 3 were assigned to the Vitamin D supplement arm and 2 were assigned to the Metformin arm.
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D (Cholecalciferol) Cholecalciferol 5,000 IU PO daily
Vitamin D: Oral medication daily | 2 |
| Metformin Metformin 1000 mg PO bid
Metformin: Oral medication daily | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Vitamin D (Cholecalciferol) | Total | Metformin |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 1 Participants |
| Beck Depression Inventory (BDI-II) | 21.5 units on a scale STANDARD_DEVIATION 4.5 | 20.33 units on a scale STANDARD_DEVIATION 4.02 | 18 units on a scale STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting Glucose | 90.5 mg/dL STANDARD_DEVIATION 3.5 | 88 mg/dL STANDARD_DEVIATION 4.54 | 83 mg/dL STANDARD_DEVIATION 0 |
| Fasting Insulin | 14.2 μIU/mL STANDARD_DEVIATION 4.6 | 20.13 μIU/mL STANDARD_DEVIATION 9.19 | 32 μIU/mL STANDARD_DEVIATION 0 |
| Fasting Insulin Resistance | 3.12 units on a scale STANDARD_DEVIATION 0.92 | 4.28 units on a scale STANDARD_DEVIATION 1.8 | 6.6 units on a scale STANDARD_DEVIATION 0 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 3 participants | 5 participants | 2 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| State-Trait Anxiety Inventory Score (STAI-S) | 54.5 units on a scale STANDARD_DEVIATION 3.5 | 51 units on a scale STANDARD_DEVIATION 5.71 | 44 units on a scale STANDARD_DEVIATION 0 |
| Vitamin D, 25 hydroxy | 21.5 ng/mL STANDARD_DEVIATION 2.5 | 21.33 ng/mL STANDARD_DEVIATION 2.05 | 21 ng/mL STANDARD_DEVIATION 0 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 0 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
Change From Baseline in Depression Score on the Beck Depression Inventory (BDI-II) at 12 Weeks
BDI-II is a validated self-reported instrument of 21 questions which are each scored 0-3. Total scores range from 0-63, with higher score totals indicating more severe depression symptoms. {0-9: indicates minimal depression; 0-18: indicates mild depression; 19-29: indicates moderate depression; 30-63: indicates severe depression}. Change = Week 12 total score - Baseline week score
Time frame: Baseline & 12 weeks
Population: In both the Vitamin D and the Metformin arms, only 1 participant in each arm was analyzed for Change in Depression from Baseline as only 1 participant in each arm participated through to week 12. A Change could not be calculated for the other 3 participants as no week 12 scores were available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Cholecalciferol) | Change From Baseline in Depression Score on the Beck Depression Inventory (BDI-II) at 12 Weeks | -8 score on a scale | Standard Deviation 0 |
| Metformin | Change From Baseline in Depression Score on the Beck Depression Inventory (BDI-II) at 12 Weeks | 7 score on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in State-Trait Anxiety Inventory Score (STAI-S) at 12 Weeks
STAI-S is a validated self-reported instrument of 20 questions. Range of scores for the State Anxiety (STAI-S) subtest is 20-80, the higher score indicating greater anxiety. A threshold point score of 39-40 has been suggested by recent literature to detect clinically significant symptoms. Change = Week 12 total score - Baseline week score
Time frame: Baseline week & Week 12
Population: In both the Vitamin D and the Metformin arms, only 1 participant in each arm was analyzed for a Change in Anxiety scores from Baseline as only 1 participant in each arm participated through to week 12. A Change could not be calculated for the other 3 participants as no week 12 scores were available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Cholecalciferol) | Change From Baseline in State-Trait Anxiety Inventory Score (STAI-S) at 12 Weeks | 0 score on a scale | Standard Deviation 0 |
| Metformin | Change From Baseline in State-Trait Anxiety Inventory Score (STAI-S) at 12 Weeks | 10 score on a scale | Standard Deviation 0 |
Secondary
Changes From Baseline Week in Insulin Resistance Score at Week 12.
Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) will be used to calculate Insulin Resistance based on fasting glucose (mg/dL) and fasting insulin (μIU/mL) blood serum assays tested at Quest Diagnostics. HOMA-IR = Fasting Insulin (uIU/mL) x Fasting Glucose (mg/dL). Healthy range is between 0.5-1.4. Values below 1.0 indicate insulin sensitivity and are optimal. Values greater than 1.9 indicate clinically significant insulin resistance.
Time frame: Baseline week & week 12
Population: In both the Vitamin D and the Metformin arms, only 1 participant in each arm was analyzed for Change in Insulin Resistance from Baseline as only 1 participant in each arm participated through to week 12. A Change could not be calculated for the other 3 participants as no week 12 serum insulin and glucose test results were available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Cholecalciferol) | Changes From Baseline Week in Insulin Resistance Score at Week 12. | 0.81 units on a scale | Standard Deviation 0 |
| Metformin | Changes From Baseline Week in Insulin Resistance Score at Week 12. | -1.2 units on a scale | Standard Deviation 0 |
Secondary
Changes From Baseline Week in Vitamin D 25-hydroxy Levels at Week 12.
Vitamin D, 25-hydroxy blood serum assays will be tested at Quest Diagnostics. Changes in values from baseline week to week 12 will be calculated. Reference ranges: optimal 30-100 ng/mL Insufficient 20-29 ng/mL deficient \<20ng/mL
Time frame: Baseline week & week 12
Population: In both the Vitamin D and the Metformin arms, only 1 participant in each arm was analyzed for Change in Vitamin D serum levels from Baseline as only 1 participant in each arm participated through to week 12. A Change could not be calculated for the other 3 participants as no week 12 serum Vitamin D test results were available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D (Cholecalciferol) | Changes From Baseline Week in Vitamin D 25-hydroxy Levels at Week 12. | 11 mg/dL | Standard Deviation 0 |
| Metformin | Changes From Baseline Week in Vitamin D 25-hydroxy Levels at Week 12. | -5 mg/dL | Standard Deviation 0 |