Association Between Vitamin D and the Development of Uterine Fibroids

Study Overview
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Brief Summary
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the aim of this randomised clinical trial study is to evaluate whether supplementation with vitamin D could inhibit the growth of uterine fibroids in reproductive stage women.

Detailed Description
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180 patients with vitamin D deficiency (12 ng/ml ≤ serum 25-hydroxyvitamin D3 < 20 ng/ml) and uterine fibroids will be randomly assigned in a ratio of 1:1 to two groups: intervention group A and control group B. 180 patients with vitamin D insufficiency (20 ng/ml ≤ serum 25-hydroxyvitamin D3 < 30 ng/ml) and uterine fibroids will be also randomly assigned in a ratio of 1:1 to two groups: intervention group C and control group D. The intervention group A will receive 1600 IU/d of vitamin D3; The intervention group C will receive 800 IU/d of vitamin D3; the control group B and the control group D will receive regular follow-up. Patients will be followed up at the same time points for 24 months. The outcome measure is the growth of uterine fibroids in different groups.

Official Title
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Association Between Vitamin D and the Development of Uterine Fibroids

Conditions
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Gynaecological Disease, Vitamin D Deficiency

Intervention / Treatment
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* Drug: Vitamin D 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients are willing to cooperate with the follow-up and sign informed consent; 2. Females aged 35-50 who are diagnosed as having uterine fibroids by transvaginal or abdominal ultrasonography; 3. The maximum average diameter of intramural myoma is ≤ 4cm，≥ 1cm; The amount of myoma is less than 4; 4. Serum 25-hydroxyvitamin D3 < 30 ng/ml, ≥ 12 ng/ml. Exclusion Criteria: 1. Patients with heavy menstrual bleeding (>80.0 mL), menstrual disorders, pelvic discomfort, infertility, or other indications for operation; 2. Patients complicated with myoma degeneration and adenomyosis that were suspected or diagnosed by ultrasound or gynecologic examination; 3. Allergic to vitamin D3; 4. Use of sexual hormone, mifepristone, gonadotropin-releasing hormone agonist (GnRHa), or other medication which is likely to interfere with uterine fibroids within 3 months; 5. Pregnancy, lactation, postmenopause, or planned pregnancy within two years; 6. Suspected or identified as other tumors of genital tract; 7. History of osteoporosis or vitamin D deficiency taking vitamin D supplements within previous one month; 8. History of autoimmune diseases, infectious diseases (tuberculosis, AIDS), autoimmune diseases, digestive system diseases (malabsorption, crohn disease, and dysentery); 9. Alanine aminotransferase (ALT) or aspartate transaminase(AST) more than 3 times of the normal upper limit, total bilirubin (TBIL) more than 2 times of the normal upper limit; 10. Creatinine levels≥1.4 mg/dL (123μmol/L) or creatinine clearance ≤ 50 mL/min; 11. History of malignant tumors; 12. Simultaneous participation in another clinical study with investigational medicinal product(s) or researcher thinks the subjects are not suitable for this trial.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vitamin D deficiency treatment group<br>patients with vitamin D deficiency (12 ng/ml ≤ serum 25-hydroxyvitamin D3 < 20 ng/ml)and uterine fibroids receive 1600 IU/day of vitamin D3 oral capsule for two years | Drug: Vitamin D 3<br>* Non-Vitamin D3 Drops group Patients in this group would take nothing.<br>|
| No Intervention: vitamin D deficiency control group<br>patients with vitamin D deficiency (12 ng/ml ≤ serum 25-hydroxyvitamin D3 < 20 ng/ml)and uterine fibroids receive regular follow-up. | |
| Experimental: vitamin D insufficiency treatment group<br>patients with vitamin D insufficiency (20 ng/ml ≤ serum 25-hydroxyvitamin D3 < 30 ng/ml) and uterine fibroids receive 800 IU/d of vitamin D3 | Drug: Vitamin D 3<br>* Non-Vitamin D3 Drops group Patients in this group would take nothing.<br>|
| No Intervention: vitamin D insufficiency control group<br>patients with vitamin D insufficiency (20 ng/ml ≤ serum 25-hydroxyvitamin D3 < 30 ng/ml)and uterine fibroids receive regular follow-up. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| volume of the total fibroids | percent change in volume of the largest fibroid compared to baseline in different groups | two years after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of subjects undergoing other medical or surgical treatment of uterine fibroids | percentage of subjects undergoing other medical or surgical treatment of uterine fibroids | two years after treatment | 
| Hypercalcemia | The level of serum calcium > 2.5 mmol/L | Two years after treatment | 
| abnormal liver function | Alanine aminotransferase (ALT) or aspartate transaminase (AST) more than 3 times of the normal upper limit, total bilirubin (TBIL) more than 2 times of the normal upper limit | Two years after treatment | 
| urinary calculus | urinary calculus | Two years after treatment | 
| abnormal renal function | Creatinine levels ≧ 1.4 mg/dL (123μmol/L) or creatinine clearance ≦ 50 mL/min | Two years after treatment | 
| volume of the largest fibroid | percent change in volume of the largest fibroid compared to baseline in different groups | One year after treatment | 
| volume of the total fibroids | percent change in volume of the total fibroids compared to baseline in different groups | One year after treatment | 
| volume of the largest fibroid | percent change in volume of the largest fibroid compared to baseline in different groups | two years after treatment |