Norethindrone Acetate vs. GnRH Agonist for Endometriosis

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Must not be taking: Hormones, Progestins, GnRH agonists

Disqualifiers: Abnormal lab tests, Bone density, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 15

Duration: 52 weeks

112 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares two treatments for women with painful endometriosis. One treatment is a hormone pill, and the other is an injection. Both aim to reduce tissue growth and pain by changing hormone levels.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but if you have been on hormone therapies like GnRH agonists, you must stop them and wait for a 'washout period' (time without taking certain medications) before joining the trial.

What data supports the effectiveness of the drug Lupron Depot (leuprolide acetate) combined with Norethindrone Acetate for treating endometriosis?

Research shows that Lupron Depot (leuprolide acetate) is effective in reducing pain symptoms associated with endometriosis, such as dysmenorrhea (painful periods) and pelvic pain, by suppressing hormone levels. Additionally, using Norethindrone Acetate as an add-back therapy can help alleviate side effects like bone mineral density loss. ^{1 2 3 4 5}

Is Norethindrone Acetate and GnRH Agonist treatment safe for humans?

Leuprolide acetate (a GnRH agonist) and norethindrone acetate have been studied for endometriosis treatment and are generally considered safe, though they can cause side effects like hot flashes, sleep disturbances, and bone mineral density loss. Add-back therapy with norethindrone acetate can help alleviate some of these side effects. ^{2 5 6 7 8}

Research Team

Ozgul Muneyyirci-Delale, M.D.

Principal Investigator

State University of New York - Downstate Medical Center

Eligibility Criteria

This trial is for pre-menopausal women over 18 with regular periods and diagnosed endometriosis, confirmed by surgery. They should be in good health, not have used certain hormone therapies recently, and agree to use double-barrier contraception. Women who are postpartum or lactating within the last 3 months, have significant abnormal lab results or Pap smears, low bone density, or a history of severe reactions to hormones are excluded.

Inclusion Criteria

I agree to use two forms of birth control or practice abstinence during the study.

I am in good health or have mild, stable conditions not related to major organ systems or mental health.

You must have a negative pregnancy test before starting the study.

Exclusion Criteria

I had an abnormal Pap smear but tested negative for high-risk HPV.

I have low bone density or a history of specific bone issues.

I've had severe side effects from hormone or GnRH treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Norethindrone Acetate (NA) or GnRH agonist (Lupron Depot) for 24 weeks, followed by NA for an additional 28 weeks

52 weeks

Visits at 12, 24, and 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3, 6, 9, and 12 months

52 weeks

Visits at 3, 6, 9, and 12 months

Treatment Details

Interventions

• Lupron Depot
• Norethindrone Acetate

Trial Overview The study compares Norethindrone Acetate (NA) with GnRH Agonist (Lupron Depot) in treating endometriosis symptoms. It aims to see if NA maintains bone density better than Lupron Depot while also assessing effects on lipid profiles and quality of life through questionnaires.

Participant Groups

Group I: LD then NA Active Control 1 Intervention

Lupron Depot(LD) given intramuscularly every 12 weeks for total of 24 weeks then switched to Norethindrone Acetate (NA) taken 1-3 tablets orally every night for remainder of treatment

Group II: NA alone Active Control 1 Intervention

Norethindrone Acetate (NA) 5mg taken 1-3 tabs orally every night for duration of treatment

Lupron Depot is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in European Union as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Canada as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Japan as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Who Is Running the Clinical Trial?

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Lead Sponsor

Trials

2,103

Recruited

2,760,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

State University of New York - Downstate Medical Center

Collaborator

Trials

67

Recruited

12,100+

References

1. England pubmed.ncbi.nlm.nih.gov

Prospective randomized study comparing the GnRH-agonist leuprorelin acetate and the gestagen lynestrenol in the treatment of severe endometriosis. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Analysis of Adherence, Persistence, and Surgery Among Endometriosis Patients Treated with Leuprolide Acetate Plus Norethindrone Acetate Add-Back Therapy. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Short-term Lupron or danazol therapy for pelvic endometriosis. [2017]

4. China pubmed.ncbi.nlm.nih.gov

[Randomized, blind, parallel-controlled and multiple-centre clinical trial on the effectiveness and safety of leuprolide acetate in the treatment of endometriosis]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Add-back therapy use and its impact on LA persistence in patients with endometriosis. [2022]

7. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

A randomized comparative study of the effect of leuprorelin acetate depot and danazol in the treatment of endometriosis. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study. [2013]