Flexofytol® for the Treatment of Endometriosis- Associated Pain

Study Overview
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Brief Summary
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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.

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

Conditions
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Endometriosis

Intervention / Treatment
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* Dietary Supplement: Flexofytol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 51 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: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Curcuma, Endometriosis-associated pain