What is the mechanism of action of this treatment?

The most common treatments for endometriosis involve hormonal therapies that aim to reduce endometrial growth and inflammation. The Levonorgestrel-containing IUD (LNG-IUD) provides localized progestin, which helps to reduce the growth of endometrial tissue and alleviate inflammation directly within the uterus. Norethindrone Acetate (NETA) adds systemic progestin, further suppressing endometrial tissue throughout the body and improving bleeding patterns and pain control. These mechanisms are crucial for endometriosis patients as they target the underlying causes of their symptoms, offering relief from chronic pain and improving quality of life.

What side effects are associated with this type of intervention?

The most common treatments for endometriosis, including Levonorgestrel-containing IUD (LNG-IUD) and Norethindrone Acetate (NETA), often have side effects related to hormonal changes. LNG-IUD can cause irregular bleeding, headaches, breast tenderness, and mood changes. NETA, a systemic progestin, may lead to weight gain, bloating, mood swings, and breakthrough bleeding. GnRH analogs, another common treatment, can induce menopausal symptoms such as hot flashes, night sweats, and decreased bone density. Oral contraceptives, used to manage endometriosis pain, may cause nausea, breast tenderness, and an increased risk of blood clots. Progestins alone can result in similar side effects, including weight gain, mood changes, and irregular bleeding.

What prior FDA approvals exist?

The FDA has approved several treatments for endometriosis that involve hormonal therapies similar to the Levonorgestrel-containing IUD (LNG-IUD) and Norethindrone Acetate (NETA). These include combined estrogen-progestin contraceptives, which are first-line treatments for endometriosis-related pain due to their long-term use, tolerability, and additional benefits. Progestin-only treatments like oral norethindrone acetate and depot medroxyprogesterone acetate have also been approved for managing endometriosis symptoms. Additionally, GnRH agonists and antagonists are used to suppress ovarian hormone production, although they come with more adverse effects. The LNG-IUD, while effective in reducing dysmenorrhea, has not been definitively proven to prevent endometrioma recurrence.

What other types of research exist?

Promising novel alternatives for endometriosis treatment in 2024 include Dienogest, which offers moderate estrogen suppression and anti-inflammatory properties, and Gonadotropin-releasing hormone (GnRH) analogs, which are highly effective at suppressing ovarian hormone production and inhibiting endometrial tissue growth. Aromatase inhibitors are also an option, particularly for patients who do not respond to other treatments.

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Hormone Therapy

IUD + Norethindrone Acetate for Endometriosis

Phase 2

Waitlist Available

Led By Amy DiVasta

Research Sponsored by Boston Children's Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 13 to 24 years

Female with surgically confirmed endometriosis

Must not have

Systemic lupus erythematosus

Impaired liver function or liver disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, 3 months, 6 months, 9 months, 12 months

Awards & highlights

All Individual Drugs Already Approved

Summary

This trial tests a combination of a hormone-releasing device placed in the uterus and a hormone pill to help young women with endometriosis manage pain and bleeding more effectively. The device releases a hormone to reduce pain, while the pill helps control bleeding and enhances the treatment's overall effectiveness.

Who is the study for?

This trial is for young females aged 13-24 with surgically confirmed endometriosis, experiencing pelvic pain. They must be planning to use an LNG-IUD and willing to follow the study's schedule and rules. It excludes those who are pre-menarche or post-menopause, have certain health conditions like liver disease or blood clots, take specific drugs affecting liver enzymes, have mental illnesses impacting pain assessment, are breastfeeding/recently gave birth/plan pregnancy soon, used certain hormone treatments before, or can't safely use an IUD.

What is being tested?

The study tests if adding Norethindrone Acetate (NETA) to a Levonorgestrel-containing IUD (LNG-IUD) improves bleeding patterns and controls pain better in adolescents and young adults with endometriosis. Participants will either receive NETA alongside their LNG-IUD treatment or a placebo without knowing which one they're getting.

What are the potential side effects?

Possible side effects include changes in menstrual bleeding patterns, abdominal discomfort or cramps related to the IUD insertion process. NETA may cause weight gain, headache, mood swings, acne and breast tenderness.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 13 and 24 years old.

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I am a woman with endometriosis confirmed by surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have systemic lupus erythematosus.

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I have liver disease or impaired liver function.

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I am not taking drugs like erythromycin or ketoconazole.

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I have used hormone therapy for reproductive health before.

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I have had blood clots in my veins or arteries.

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I have not started menstruating or I am post-menopausal.

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My diabetes or high blood pressure is not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, 3 months, 6 months, 9 months, 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, 3 months, 6 months, 9 months, 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, 3 months, 6 months, 9 months, 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Emotional functioning, assessed by the Beck Depression Inventory-II (BDI)

Change in Pain-Physical functioning assessed by the BPI

Change in Participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale (PGIC)

+2 more

Secondary study objectives

Change in Bone mineral density Z-scores by dual energy Xray absorptiometry (DXA)

Change in Factor VIII activity

Change in Measure of arterial stiffness by pulse wave velocity

+9 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: LNG IUD+ Norethindrone AcetateExperimental Treatment1 Intervention

All eligible participants will have the LNG-IUD. Experimental participants will also receive norethindrone acetate 5 mg by mouth daily for 12 months.

Group II: LNG IUD+PlaceboPlacebo Group1 Intervention

All eligible participants will have the LNG-IUD. Participants in the placebo comparator group will also receive a placebo tablet, 1 tablet by mouth daily for 12 months.

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for endometriosis involve hormonal therapies that aim to reduce endometrial growth and inflammation. The Levonorgestrel-containing IUD (LNG-IUD) provides localized progestin, which helps to reduce the growth of endometrial tissue and alleviate inflammation directly within the uterus. Norethindrone Acetate (NETA) adds systemic progestin, further suppressing endometrial tissue throughout the body and improving bleeding patterns and pain control. These mechanisms are crucial for endometriosis patients as they target the underlying causes of their symptoms, offering relief from chronic pain and improving quality of life.

The evaluation of the effectiveness of an intrauterine-administered progestogen (levonorgestrel) in the symptomatic treatment of endometriosis and in the staging of the disease.