IUD + Norethindrone Acetate for Endometriosis

Overseen By Jenny Gallagher

Age: < 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Boston Children's Hospital

Must be taking: LNG-IUD

Must not be taking: CYP34a inducers/inhibitors

Disqualifiers: Liver disease, Lupus, Uncontrolled diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for managing endometriosis, a condition that causes severe pelvic pain and affects daily life for many young women. Researchers are examining whether adding a daily pill called norethindrone acetate (a type of hormone therapy) to the levonorgestrel-releasing IUD (a type of long-term birth control) can better control pain and improve bleeding patterns. Participants will receive either the IUD with a placebo (a pill with no active ingredients) or the IUD with norethindrone acetate. Women aged 13 to 24 with confirmed endometriosis and ongoing pelvic pain may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in endometriosis care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain drugs like erythromycin, ketoconazole, phenobarbital, or rifampin. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that norethindrone acetate (NETA) is generally safe and well-tolerated. One study found that women with endometriosis who took NETA for five years considered it safe and manageable. This is why it is commonly used to treat endometriosis symptoms. However, it may cause side effects such as changes in bleeding patterns, headaches, or nausea.

The levonorgestrel-containing IUD (LNG-IUD), also part of the trial, is recognized for its safety. Many users find the LNG-IUD safe, though it can cause side effects like irregular bleeding.

Overall, research indicates that both treatments are safe for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometriosis?

Researchers are excited about using norethindrone acetate with an LNG-IUD for endometriosis because it combines a hormonal IUD, which is known for local hormone delivery, with an oral progestin that targets systemic symptoms. Most treatments for endometriosis, like GnRH agonists or oral contraceptives, primarily aim to regulate hormones or reduce inflammation. However, norethindrone acetate offers a dual action by not only alleviating pain but also potentially reducing lesions more effectively. This combination could offer a more comprehensive approach to managing endometriosis symptoms compared to standard hormonal treatments.

What evidence suggests that this trial's treatments could be effective for endometriosis?

Research has shown that norethindrone acetate (NETA) effectively manages pain caused by endometriosis. Studies have found that NETA not only provides significant pain relief but also reduces the size of endometriomas, cysts associated with endometriosis. NETA is considered safe and well-tolerated for long-term use. In this trial, participants will receive a levonorgestrel-releasing IUD, a type of birth control device. Some participants will also receive NETA, which may improve bleeding patterns and further aid in pain management. Overall, NETA is regarded as a strong option for treating symptoms of endometriosis. ^{1 2 4 6 7}

Who Is on the Research Team?

Amy DiVasta, MD, MMSc

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have had pelvic pain rated 3 or higher for at least 2 months.

I am starting to use the LNG-IUD for birth control.

I am between 13 and 24 years old.

Exclusion Criteria

I have systemic lupus erythematosus.

I have liver disease or impaired liver function.

You are allergic to any part of the NETA or LNG-IUS.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either LNG IUD with placebo or LNG IUD with norethindrone acetate for 12 months

12 months

Monthly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Norethindrone Acetate
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: LNG IUD+ Norethindrone Acetate Experimental Treatment 1 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+Placebo Placebo Group 1 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.

Norethindrone Acetate is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Aygestin for:

• Endometriosis
• Abnormal Uterine Bleeding
• Amenorrhea
• Birth Control

Approved in Canada as Norlutate for:

• Endometriosis
• Abnormal Uterine Bleeding
• Amenorrhea
• Birth Control

Approved in European Union as Primolut-Nor for:

• Endometriosis
• Abnormal Uterine Bleeding
• Amenorrhea
• Birth Control
• Menopausal hormone therapy

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40233572/

Norethindrone acetate versus dienogest for pain relief in ... Conclusions: Both progestins effectively reduced pain scores, but NETA achieved a greater reduction in endometrioma size and had a lower dropout ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301211517301471

Efficacy and acceptability of long-term norethindrone ... Conclusion. Five-year therapy with NETA is safe and well tolerated by women with rectovaginal endometriosis. Due to its low cost and good pharmacological ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05476172?term=AREA%5BInterventionSearch%5D(MICRONOR)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=2

The Effect of Dienogest vs. Norethindrone Acetate ... This randomized controlled study aims to investigate the efficiency of medical treatment modalities in endometriosis patients. The study protocol involves ...

4. bmcwomenshealth.biomedcentral.com bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-022-02122-0

Progestins in the symptomatic management of endometriosis The meta-analysis revealed that pain improvement significantly increased with the use of progestins with low adverse effects.

5. academic.oup.com academic.oup.com/humrep/article/38/Supplement_1/dead093.696/7203550

P-338 Preliminary results of the DINE Study (Dienogest vs ... It has a good safety profile and efficacy in curing endometriosis-related pain, making NETA a viable medical option among first-line treatments.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2007/018405s023lbl.pdf

AYGESTIN (norethindrone acetate tablets, USP) Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with AYGESTIN®.

7. my.clevelandclinic.org my.clevelandclinic.org/health/drugs/20808-norethindrone-acetate-tablets-hormone-replacement-therapy

Norethindrone Acetate: Uses & Side Effects Norethindrone acetate treats endometriosis, uterine bleeding caused by abnormal hormone levels and secondary amenorrhea.