Glycemic Regulation as Endometriosis Adjunct Treatment
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age15-35
SponsorBoston Children's Hospital
About this trial
The goal of this pilot trial is to learn if a novel non-hormonal treatment, metformin hydrochloride, works to treat pelvic pain in young women with endometriosis. The main questions it aims to answer are:
* Is metformin superior to placebo in alleviating pain symptoms in young women with endometriosis? * Does metformin alter systemic inflammatory markers over 6 months in young women with endometriosis?
Researchers will compare metformin to a placebo (a look-alike substance that contains no drug) to see if metformin works to treat pelvic pain.
Participants will:
* Take drug metformin or a placebo every day for 6 months * Visit the clinic three times: once at baseline (pre-treatment), once at 3 months, and once at 6 months * Keep a daily symptom diary to track pain, bleeding, and usage of any pain medications
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Female with surgically confirmed endometriosis, determined at laparoscopy
Current use for at least 2 months duration of a consistent hormonal therapy for endometriosis (either combination hormonal contraceptives or progestin-only therapy)
Current pelvic pain (score ≥ 3 on Visual Analog Scale) that has been present for at least 2 months prior to enrollment
Age 15 years to 35 years and premenopausal
Disqualifiers
Pre-menarche or post-menopause
Diagnosis of Type 1 or Type 2 Diabetes Mellitus
Severe renal dysfunction (creatinine >1.4 mg/dL or eGFR below 45 mL/minute/1.73 m2
History of lactic acidosis or diabetic ketoacidosis
Trial design
Design model
Parallel
Treatments tested in this trial
Metformin Hydrochloride
DrugMetformin dosage titrated from 500 mg/daily for 2 weeks, then 1000 mg/daily for 2 weeks, 1500 mg/daily for 2 weeks, and then achieving 2000 mg/daily for a duration of 6 months of treatment.
Placebo
Drug1 tablet orally with evening meal for 2 weeks, then 1 tablet twice daily for 2 weeks, then 3 tablets split twice daily for 2 weeks, then 4 tablets split twice daily, for a total of 6 months of treatment.
Treatment groups
14 Participants
are divided into 2 treatment groupsGroup A: PlaceboPlacebo comparator 1 intervention
Group B: MetforminExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Change in pain assessed by the Brief Pain Inventory Interference Scale (BPI) over 6 months
The BPI Interference Scale is a 7-item composite pain measurement. This self-report measure assesses the extent to which pain interferes with various components of physical and emotional functioning and sleep. The items in this scale can be grouped into those that assess physical functioning (general activity; walking ability; normal work, including both work outside the home and housework), those that assess emotional functioning (mood; relations with people; enjoyment of life), and a single item that assess the extent to which pain interferes with sleep. The arithmetic mean of the seven interference items can be used as a measure of pain interference. The BPI is anchored between a scale of zero (no pain/interference) to ten (maximum pain/interference). The magnitude of treatment-associated change in BPI Interference Scale scores in open-label and randomized clinical trials ranges from 1 to 3 points, depending on the specific pain conditions and treatments studied.
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)2
Change in pain severity measured by Visual Analog Scale (VAS) over 6 months
VAS: A measurement of pain intensity, assessed by a 0 to 10 numerical rating scale, to rate maximum and average pain intensity over the preceding 7 days. Higher scores indicate more severe pain intensity.
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)3
Change in emotional functioning assessed by Beck Depression Inventory-II (BDI) over 6 months
The BDI is a 21-item self-report instrument that provides a rapid assessment of depressive symptoms. BDI has been used in many studies of chronic pain, including chronic pelvic pain and endometriosis. Total scores on the BDI range from 0 to 63. The BDI takes about 5-10 minutes to complete. Scores below 13 should be considered to reflect "minimal or no" depression, with score ranges of 14 to 19, 20 to 28, and 29 to 63 reflect "mild to moderate," "moderate to severe," and "severe" depression, respectively.
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)4
Change in ratings of overall improvement assessed by the Patient Global Impression of Change scale (PGIC)
The PGIC is a seven-point single-item scale with options ranging from 'very much worse' to 'very much improved'. There has been widespread use of the PGIC in recent endometriosis clinical trials, as it readily interprets a person's evaluation of the importance of their improvement or worsening.
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)Secondary outcomes
1
Change in quality of life, measured via Endometriosis Health Profile-30 (EHP-30)
The EHP-30 is a reliable instrument and recommended by the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. The questionnaire includes 30 questions in five subcategories, with each category addressing specific problem areas of pain, control and powerlessness, emotional wellbeing, social support, and self-image.
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)2
Changes in sexual satisfaction for participants who are sexually active measured by the New Sexual Satisfaction Scale
The NSSS is a 20-item measure assessing sexual sensations, sexual presence/awareness, sexual exchange, emotional connection/closeness, and sexual activity. The full scale takes 5 minutes to complete.
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)3
Complete health and medication history assessed by the World Endometriosis Research Foundation (WERF) questionnaire
Study participants will complete an expanded version of the WERF questionnaire for a complete health and medication history
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)4
Changes in serum angiogenic/inflammatory markers
Serum samples will also be obtained for measures of inflammation, to test the hypothesis that endometriosis-relevant inflammatory markers will decrease over time in patients treated with metformin compared to those receiving placebo. These markers will include IL-6, IL-8, and VEGF based on the results of prior studies in which metformin appeared to reduce these levels in humans with endometriosis and from endometriotic implants in rats. C-reactive protein (CRP) will also be assessed; CRP has been shown to be upregulated, especially when examined with a high sensitivity assay making it possible to detect subclinical inflammation in women with endometriosis.
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)Other outcomes
1
Changes in school and/or work attendance
School and/or work attendance will be assessed at each visit.
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)2
Change in pregnancy status
Urine pregnancy test throughout the study as current pregnancy is an exclusion criteria
Time frame
once at each of the three visits (at baseline, 3 months, 6 months)3
Changes in serum lactate levels
Serum lactate will be measured at baseline and then possibly at three and six months, if needed.
Time frame
baseline, three and six months if needed4
Changes in pain
Subjects will keep a daily symptom diary to track pain for 6 months.
Time frame
daily for 6 monthsSponsors and contacts
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Source ClinicalTrials.gov