Association Between Vitamin D and the Development of Uterine Fibroids

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.

Study Overview

• Status: Unknown
• Conditions: Vitamin D Deficiency; Gynaecological Disease
• Intervention / Treatment: Drug: Vitamin D 3

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xueqiong Zhu, PHD; Phone Number: 13906640759; Email: zjwzzxq@163.com

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • The second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
      • Contact: TING LI; Email: feclinicalresearch@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vitamin D deficiency treatment group; 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; Non-Vitamin D3 Drops group Patients in this group would take nothing.
No Intervention: vitamin D deficiency control group; 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; 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; Non-Vitamin D3 Drops group Patients in this group would take nothing.
No Intervention: vitamin D insufficiency control group; 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?

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University

Publications and helpful links

General Publications

• Sheng B, Song Y, Liu Y, Jiang C, Zhu X. Association between vitamin D and uterine fibroids: a study protocol of an open-label, randomised controlled trial. BMJ Open. 2020 Nov 6;10(11):e038709. doi: 10.1136/bmjopen-2020-038709.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 15, 2018
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: June 13, 2018
• First Submitted That Met QC Criteria: June 28, 2018
• First Posted (Actual): July 12, 2018

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: September 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Nutrition Disorders; Connective Tissue Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Vitamin D Deficiency; Leiomyoma; Myofibroma; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: SAHoWMU-CR2017-07-126

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No