Flexofytol® for the Treatment of Endometriosis- Associated Pain (ENDOFLEX)

Flexofytol®, a Curcuma Extract, for the Treatment of Endometriosis- Associated Pain: a Randomized, Double Blind, Placebo-controlled Study

Endometriosis is a benign disease that affects 6-10% of women of reproductive age. The wide range of symptoms observed in patients with endometriosis is due to implantation of endometrial tissue outside the uterine cavity. This ectopic endometrium is subjected to cyclic changes similar to that of eutopic endometrium. Typically, ectopic lesions are found in the pelvis, notably on the ovaries in the form of cysts (endometriomas), as well as the rectouterine and vesicouterine pouch. Lesions have also been described in other parts of the abdomen and in other locations outside the abdominal cavity.

Although endometriosis has also been described in asymptomatic patients, possible symptoms range from mild to severe pain presenting itself as dysmenorrhea, dyspareunia, or dyschezia, or as infertility. Since the clinical picture varies, the treatment of this disease has become quite personalized. Many studies conducted over the past several years have presented different treatment options for the symptoms caused by endometriosis.

Turmeric, which is won from the rootstalks of Curcuma longa, has more than 300 biologically active elements. One of the three main curcuminoids that are derived from turmeric, is curcumin. Several in-vitro and animal studies have described anti-oxidant, anti-inflammatory and anti-angiogenic effects of curcumin.

The main objective for the treatment of endometriosis patients is symptom relief. Treatment options include analgesic therapies, hormonal therapies, laparoscopic surgery or a combination of these. For patients who refuse hormonal therapies however, conservative treatment options are limited.

Curcuma is a substance that has been in use for centuries, especially in ayurvedic and Traditional Chinese Medicine for the treatment of various symptoms, notably for pain alleviation in inflammatory illnesses. Several recently published studies have shown very promising results of Flexofytol for pain alleviation in patients with osteoarthritis, due to its anti-inflammatory and anti-oxidant properties. Due to these properties of curcuma, we aim to analyse if curcuma capsules, sold by the pharmaceutical company Tilman under the name Flexofytol®, can be used to alleviate symptoms in patients suffering from endometriosis.

Study Overview

• Status: Unknown
• Conditions: Endometriosis
• Intervention / Treatment: Dietary supplement: Flexofytol; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • General Hospital of Vienna, Medical University of Vienna
    • Contact: René Wenzl, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Premenopausal women between the ages of 18 and 51 years
• Ability to comprehend the full nature and purpose of the study
• Signed informed consent
• Diagnosed endometriosis (peritoneal, ovarian or deep-infiltrating endometriosis (DIE))
• By laparoscopy or laparotomy with histological verification diagnosed up to 10 years before screening
• By ultrasound or MRI (ovarian or deep-infiltrating endometriosis, as peritoneal lesions can only be evaluated surgically)
• Moderate to severe pelvic pain (i.e. dysmenorrhea or NMPP of at least 4 on the 1-10 NRS) at least during the past 3 months
• Refusal of hormonal treatments
• The patient must agree to switch from her usual analgesic rescue medication to only the one permitted by the study during screening, treatment and follow-up period

Exclusion Criteria:

• The patient is pregnant or breast feeding or is planning a pregnancy within the treatment period
• Known addiction (alcohol, drugs, pills, etc...)
• Liver or kidney problems
• Known problems of the bile system
• Infection (HIV, Hepatitis, TBC, etc..) or systemic autoimmune diseases
• Known or suspected malignant disease
• Intake of blood-thinning medication (such as heparin or aspirin for example)
• Intake of hormonal contraceptives (oral during the last 4 weeks, injectable: during the last 3 months)
• Patient with a surgical history of hysterectomy, bilateral adnexectomy, endometrial ablation resulting in amenorrhea

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Flexofytol; 2 capsules containing 42mg of curcumin will be administered twice a day for a duration of 4 months.	Dietary supplement: Flexofytol; Curcuma extract
Placebo Comparator: Placebo; 2 capsules of the placebo, identical in appearance to Flexofytol, will be administeres twice a day for a duration of 4 months.	Other: Placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the average pain score from baseline to 4 months after begin of treatment	Pain will be evaluated using the Numeric Rating Scale (NRS), from 0 (no pain) to 10 (worst pain imaginable).	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of days with pain ≥ NRS 4 from baseline to 4 months after begin of treatment	Pain will be evaluated using the Numeric Rating Scale (NRS), from 0 (no pain) to 10 (worst pain imaginable).	4 months
Alleviation of dyspareunia using the NRS between 0 and 10, from baseline to 4 months after begin of treatment points)	Pain will be evaluated using the Numeric Rating Scale (NRS), from 0 (no pain) to 10 (worst pain imaginable).	4 months
Alleviation of dysuria using the NRS between 0 and 10 points, from baseline to 4 months after begin of treatment	Pain will be evaluated using the Numeric Rating Scale (NRS), from 0 (no pain) to 10 (worst pain imaginable).	4 months
Alleviation of dyschezia using the NRS between 0 and 10 points from baseline to 4 months after begin of treatment	Pain will be evaluated using the Numeric Rating Scale (NRS), from 0 (no pain) to 10 (worst pain imaginable).	4 months
Change in quality of life (using the numerical score of the Endometriosis health profile - EHP 30)	evaluated using a scale of 0 - 100, where 0 indicates the best health status and 100 the worst health status	4 months
Change in sexual function (using the numerical score of the female sexual function index - FSFI)	each question answered using a score from 0 to 5, 0 indicating no sexual activity, and, depending on the question, 1 indicating high satisfaction or high frequency, to 5 indicating low satisfaction or low frequency.	4 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2019
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Curcuma; Endometriosis-associated pain
• Additional Relevant MeSH Terms: Endometriosis
• Other Study ID Numbers: 1712/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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