FATIMA Trial: EGCG and Vitamin D3 for Prevention of Fibroid Recurrence (FATIMA)

FATIMA Trial: EGCG and Vitamin D3 for Secondary Prevention of Uterine Fibroids

The aim of this randomized controlled clinical trial is to evaluate the efficacy of green tea (EGCG) and vitamin D3 supplementation in preventing uterine fibroid recurrence following fibroid removal.

Study Overview

• Status: Recruiting
• Conditions: Uterine Fibroids (Leiomyoma)
• Intervention / Treatment: Combination product: Vitamin D and Green Tea; Other: Placebo

Detailed Description

Uterine leiomyomas (fibroids) are the most common benign hormone-dependent tumors affecting approximately 50% to 70% of reproductive-age women. Although many fibroids remain asymptomatic, they may cause abnormal uterine bleeding, pelvic pain, anemia, and infertility. Myomectomy is an effective uterus-preserving surgical treatment; however, fibroid recurrence following surgery remains common, and there is currently no established medical strategy for recurrence prevention.

This randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy of Epigallocatechin gallate (EGCG) and vitamin D3 supplementation in preventing fibroid recurrence following myomectomy. EGCG and vitamin D3 have demonstrated antifibrotic, anti-inflammatory, and antiproliferative properties in preclinical and clinical studies and may represent a potential non-hormonal preventive approach.

Premenopausal women undergoing myomectomy for symptomatic uterine fibroids will be randomized into two groups in a 2:1 ratio to receive either (1) daily oral EGCG (300 mg) and vitamin D3 (2000 IU), or (2) placebo, in addition to standard post-surgical care. The intervention period will continue for 24 months following surgery.

The primary outcome is fibroid recurrence, assessed by transvaginal ultrasound during scheduled follow-up visits postoperatively. Secondary outcomes include fibroid volume, symptom recurrence, quality-of-life measures, and need for reintervention.

Follow-up assessments will include symptom evaluation, questionnaire completion, medication compliance assessment, concomitant medication review, adverse event monitoring, ultrasound evaluation, and predefined safety laboratory investigations according to the study schedule. Statistical analyses will evaluate recurrence rates and treatment efficacy between groups.

The results of this trial will provide evidence regarding the effectiveness of EGCG and vitamin D3 as a potential non-hormonal strategy for the prevention of uterine fibroid recurrence following myomectomy.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tonianne J Grobmyer, Physician Associate; Phone Number: +971 800 7762 800; Email: tonianne.grobmyer@ku.ac.ae
• Study Contact Backup: Name: Leen Oyoun Alsoud, Master Pharmaceutical Sciences; Phone Number: +971 800 7762; Email: 100066957@ku.ac.ae

Study Locations

• United Arab Emirates
  • United Arab Emirates (uae)
    • Abu Dhabi, United Arab Emirates (uae), United Arab Emirates, 00000
      • Recruiting
      • Sheikh Shakbhout Medical City
      • Contact: Phone Number: +971 2 312 3974; Email: tonianne.grobmyer@ku.ac.ae

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Inclusion Criteria (all inclusion criteria must have been met before randomization unless otherwise specified and exceptions to inclusion criteria may be made at the discretion of the Principal Investigator, provided they are justified and ensure no compromise to the study's scientific integrity or participant safety):

Inclusion Criteria:

1. Has voluntarily signed and dated the informed consent form before initiation of any screening or study-specific procedures.
2. Premenopausal females aged 18 years and older on the day of signing of the informed consent form.
3. Has a diagnosis of uterine fibroids that is confirmed by a pelvic ultrasound (transvaginal and/or transabdominal) performed during the screening period.

4. Has at least one or more of the following symptoms:

   1. Moderate to heavy menses defined as PBAC score ≥ 120
   2. Pelvic pain during menses measured on NRS ≥ 4 at baseline
   3. Moderately severe fibroid-related symptoms (a score ³ 25 on the UF quality of life symptoms severity subscale).
5. Has a negative urine pregnancy test at the Screening, Baseline, and interval clinic visits

6. Agrees to not be pregnant for at least 12 months. Participants may use any form of non-hormonal contraception consistently during the screening period and the randomized treatment period. These may include Diaphragm, cervical cap, spermicides, male and female condoms, copper IUD and sponge. Each one will be explained in detail for the participants. However, the patient is not required to use contraception if she:

   1. Has a sexual partner(s) who was vasectomized at least 6 months before the screening period.
   2. Had a bilateral tubal occlusion (including ligation and blockage methods such as Essure™), at least 4 months prior to the first screening visit (patients with Essure™ must have prior confirmation of tubal occlusion by hysterosalpingogram).
   3. Is not sexually active with men; periodic sexual relationship(s) with men requires the use of dual non-hormonal contraception as noted above; or
   4. Practices total abstinence from sexual intercourse as her preferred lifestyle; periodic abstinence is not acceptable.
7. Has an endometrial (aspiration) biopsy, if clinically indicated, performed during the screening period, with results showing no clinically significant endometrial pathology (hyperplasia, endometritis, or endometrial cancer).

Exclusion Criteria:

1. Participants with documented vitamin D deficiency (based on previous serum vitamin D level within prior 12 months).
2. Has transvaginal and/or transabdominal ultrasound during the screening period demonstrating pathology other than uterine fibroids that could be responsible for or contributing to the patient's heavy menstrual bleeding, such as uterine or cervical polyps > 2.0 cm, or any other clinically significant gynecological disorder determined by the investigator to require further evaluation and/or treatment.
3. Has unexplained vaginal bleeding outside of the patient's regular menstrual cycle.
4. Has undergone ultrasound-guided laparoscopic radiofrequency ablation, or any other surgical procedure for fibroids, uterine artery embolization, magnetic resonance-guided focused ultrasound for fibroids, as well as endometrial ablation for abnormal uterine bleeding within 6 months prior to the screening visit.
5. Has a history of or currently has osteoporosis, or other metabolic bone disease, hyperparathyroidism, hyperprolactinemia, hyperthyroidism, anorexia nervosa, or low traumatic (from the standing position) or atraumatic fracture (toe, finger, skull, face, and ankle fractures are allowed). A history of successfully treated hyperparathyroidism, hyperprolactinemia, or hyperthyroidism is allowed if the patient's bone mineral density is within normal limits.
6. Has a history of the use of bisphosphonates, calcitonin, calcitriol, ipriflavone, teriparatide, denosumab, or any medication other than calcium and vitamin D preparations to treat bone mineral density loss
7. Anticipated use of systemic glucocorticoids at an oral prednisone-equivalent dose of more than 5 mg every other day during the study. Note: topical, inhaled, intranasal, optic, ophthalmic, intraarticular, or intralesional subcutaneous are permitted without restriction.
8. Gastrointestinal disorder affecting absorption or gastrointestinal motility
9. Has jaundice or known current active liver disease from any cause, including hepatitis A (HAV IgM), hepatitis B (HBsAg), or hepatitis C (HCV Ab positive, confirmed by HCV RNA).
10. Has any of the following cervical pathology: high-grade cervical neoplasia, atypical glandular cells, atypical endocervical cells, atypical squamous cells favoring high grade. Of note, patients with atypical squamous cells of undetermined significance and low-grade cervical neoplasia may be included in the study if high-risk human papillomavirus testing is negative or if DNA testing for human papillomavirus 16 and 18 DNA testing is negative
11. Has any history of clinical laboratory abnormalities indicating hepatic or gallbladder impairment.
12. Has been a participant in an investigational drug or device study within the 1 month prior to the screening visit.

13. Has a history of clinically significant condition(s) including, but not limited to:

    1. Untreated thyroid dysfunction or palpable thyroid abnormality (patients with adequately treated hypothyroidism who are stable on medication are not excluded).
    2. History of malignancy within the past 5 years or ongoing malignancy other than curatively treated nonmelanoma skin cancer or surgically cured Stage 0 in situ melanoma.
14. Any current psychiatric disorder that would, in the opinion of the investigator or medical monitor, impair the ability of the patient to participate in the study or would impair the interpretation of their data. Patients with major depression, post-traumatic stress disorder, bipolar disorder, schizophrenia, or other psychotic disorders, based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria who have been unstable based on the investigator's or mental health professional's judgement or whose psychiatric drug regimen has changed during the 3 months prior to Screening or is expected to change during the study should not be enrolled. Has a contraindication or history of sensitivity to any of the study treatments or components thereof; or has a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates study participation.
15. Has a prior (within 1 year of Screening 1 visit) or current history of drug or alcohol abuse disorder according to Diagnostic and Statistical Manual of Mental Disorders V (all patients must be questioned about their drug and alcohol use, and this should be documented in the electronic case report form).
16. Has participated in a previous clinical study that included the use of Green tea or Vitamin D3 or has received this treatment within 3 months of the study.
17. Is inappropriate for participation in this study for other reasons, as determined by the investigator, sub-investigator, or medical monitor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational arm; Treatment with EGCG and vitamin D3 tablets for up to 2 years following surgical myomectomy. Each tablet contains 150 mg EGCG and 1000 IU vitamin D3, and participants will take one tablet twice daily, providing a total daily dose of 300 mg EGCG and 2000 IU vitamin D3 (n=160).	Combination product: Vitamin D and Green Tea; EGCG and Vitamin D3 (300 mg, 2000 IU respectively, in tablets Each tablet will contain 150 mg EGCG, 1000 IU Vitamin D
Placebo Comparator: Placebo arm; Treatment with placebo after surgical myomectomy (n=80).	Other: Placebo; The placebo has no medication and the participant will receive standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibroid Recurrence	The primary outcome is: Fibroid recurrence when compared to the post-myomectomy baseline pelvic ultrasound (transvaginal and/or transabdominal), defined as a new fibroid identified on ultrasound with volume >1 cm3.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return of moderate to heavy menses	Return of moderate to heavy menses defined as PBAC score ≥ 120 for patients with pre-operative moderate to heavy menses. PBAC stands for Pictorial Blood Loss Assessment Chart. In this chart, there is no unit. In this Chart, the higher the number, the heavier the menses.	2 years
Need for reintervention	Need for reintervention defined as the need to undergo a procedure or surgery for treatment of uterine fibroids including repeat myomectomy, uterine fibroid embolization, and radiofrequency ablation. In this outcome, we will examine the participant info at each evaluation visit to capture the data if she has undergone any anti-fibroid procedure or surgery. The captured data will be: "Yes" or "No".	2 years
Time to event	Time to event (procedure or surgery) such as radiofrequency ablation (RFA), myomectomy, hysterectomy, or uterine fibroid embolization (UFE). The unit for this outcome is "weeks". In this outcome, we will examine the patient info at each evaluation visit to calculate the number of "weeks" it took a participant to need to undergo an anti-fibroid procedure or surgery.	2 years
Symptom recurrence	Symptom recurrence according to the Uterine fibroid quality of life symptoms severity subscale. There is no unit for this outcome. Higher score values are indicative of greater symptom severity and lower scores will indicate minimal symptom severity.	2 years
Return of pelvic pain	Return of pelvic pain during menses as measured on the validated Numerical Rating Scale. There is no unit for this outcome. Higher scores will be indicative of greater pain.	2 years
Uterine Fibroid-related Quality of life	Quality of life as measured by Patient Reported Outcome and validated Quality of life questionnaire (UFS-QOL stands for Uterine Fibroid Symptoms-Quality of Life). There is no unit for this outcome. Higher scores will be indicative of better quality of life.	2 years

Collaborators and Investigators

• Sponsor: Sheikh Shakhbout Medical City
• Investigators: Principal Investigator: Ayman Al Hendy, M.D. Ph.D., Sheikh Shakbhout Medical City; Principal Investigator: Basel Imam, M.D., Sheikh Shakbhout Medical City

Publications and helpful links

General Publications

• Roshdy E, Rajaratnam V, Maitra S, Sabry M, Allah AS, Al-Hendy A. Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. Int J Womens Health. 2013 Aug 7;5:477-86. doi: 10.2147/IJWH.S41021. eCollection 2013.
• Zhang D, Al-Hendy M, Richard-Davis G, Montgomery-Rice V, Rajaratnam V, Al-Hendy A. Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells. Fertil Steril. 2010 Oct;94(5):1887-93. doi: 10.1016/j.fertnstert.2009.08.065. Epub 2009 Oct 12.
• Sharan C, Halder SK, Thota C, Jaleel T, Nair S, Al-Hendy A. Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase. Fertil Steril. 2011 Jan;95(1):247-53. doi: 10.1016/j.fertnstert.2010.07.1041. Epub 2010 Aug 23.
• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, Critchley HOD, Li Y, McKain L, Arjona Ferreira JC, Langenberg AGM, Wagman RB, Stewart EA. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. N Engl J Med. 2021 Feb 18;384(7):630-642. doi: 10.1056/NEJMoa2008283.
• Halder SK, Goodwin JS, Al-Hendy A. 1,25-Dihydroxyvitamin D3 reduces TGF-beta3-induced fibrosis-related gene expression in human uterine leiomyoma cells. J Clin Endocrinol Metab. 2011 Apr;96(4):E754-62. doi: 10.1210/jc.2010-2131. Epub 2011 Feb 2.
• Vafaei S, Ciebiera M, Omran MM, Ghasroldasht MM, Yang Q, Leake T, Wolfe R, Ali M, Al-Hendy A. Evidence-Based Approach for Secondary Prevention of Uterine Fibroids (The ESCAPE Approach). Int J Mol Sci. 2023 Nov 4;24(21):15972. doi: 10.3390/ijms242115972.
• Halder SK, Sharan C, Al-Hendy A. 1,25-dihydroxyvitamin D3 treatment shrinks uterine leiomyoma tumors in the Eker rat model. Biol Reprod. 2012 Apr 19;86(4):116. doi: 10.1095/biolreprod.111.098145. Print 2012 Apr.
• Zhang D, Al-Hendy M, Richard-Davis G, Montgomery-Rice V, Sharan C, Rajaratnam V, Khurana A, Al-Hendy A. Green tea extract inhibits proliferation of uterine leiomyoma cells in vitro and in nude mice. Am J Obstet Gynecol. 2010 Mar;202(3):289.e1-9. doi: 10.1016/j.ajog.2009.10.885. Epub 2010 Jan 13.
• Zhang D, Rajaratnam V, Al-Hendy O, Halder S, Al-Hendy A. Green tea extract inhibition of human leiomyoma cell proliferation is mediated via catechol-O-methyltransferase. Gynecol Obstet Invest. 2014;78(2):109-18. doi: 10.1159/000363410. Epub 2014 Jun 18.

Study record dates

Study Major Dates

• Study Start (Estimated): August 22, 2026
• Primary Completion (Estimated): August 22, 2029
• Study Completion (Estimated): December 22, 2029

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Vitamin D3; Myomectomy; Uterine fibroids; EGCG
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue; Leiomyoma; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Beverages; Plant Preparations; Biological Products; Complex Mixtures; Secosteroids; Vitamin D; Tea
• Other Study ID Numbers: SSMCCREC-678; DOH/ADHRTC/2025/1994 (Registry Identifier: Department of Health of Abu Dhabi (DOH))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The Principal Investigator and study staff will ensure that the subject's privacy will be strictly maintained and that their identities are protected from unauthorized parties. This will be accomplished by securing all study documents and subject information. These files will be accessible to study staff only and maintained in a secure study office. The study staff will assign a code (numbers and/or letters) to the subject for data analysis. Documents that contain identifiers will be kept in a locked research office and/or stored within computers with password protection and encryption. We will safeguard patients' expectation that the information they offer will be held in confidence. We will protect each participant's information as prescribed by the University and Hospital policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No