IUD and Norethindrone Acetate for Treatment of Endometriosis

NCT04948489 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IRB-P00037934
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Endometriosis is the most common reproductive disease afflicting young women, often leading to debilitating chronic pelvic pain and impaired quality of life. Safe, effective, and convenient long-term treatments are lacking for adolescents and young adults. The levonorgestrel-containing IUD (LNG-IUD) represents an attractive long-term drug delivery system for the treatment of endometriosis during adolescence and young adulthood. However, while the LNG-IUD has an acceptable safety profile, it is not associated with a favorable bleeding profile and may not fully suppress endometriosis pain when used as monotherapy. Investigators hypothesize that the addition of NETA will improve bleeding patterns, maximize pain control, and improve continuation rates of the IUD when the two medications are used in combination. This proposed prospective trial provides the ideal context in which to investigate these clinical questions and advance research on the best treatments for endometriosis.

Conditions

Endometriosis

Outcome Measures

Primary Outcomes (5)

• Change in Pain-Physical functioning assessed by the BPI

  A 7-item self-report measure. 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 assesses the extent to which pain interferes with sleep. Either the item asking about the "worst pain" or the arithmetic mean of the four severity items can be used as measures of pain severity; 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.

  Baseline, 3 Months, 6 Months, 9 Months, 12 Months

• Change in pain severity measured by Visual Analog Scale (VAS)

  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.

  Baseline, 3 Months, 6 Months, 9 Months, 12 Months

• Change in pain measured by Biberoglu and Behrman patient ratings scale (B&B pain scale)

  Biberoglu and Behrman patient ratings scale (B\&B pain scale): Survey that assesses dyspareunia, dysmenorrhea, and noncyclic pelvic pain. Each is graded on a scale from 0 to 3, with higher numbers indicating more severe symptoms.

  Baseline, 3 Months, 6 Months, 9 Months, 12 Months

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

  Beck Depression Inventory-II (BDI)130, a 21-item self-report instrument that provides a rapid assessment of depressive symptoms.Total scores on the BDI range from 0 to 63. Scores below 10 should be considered to reflect "minimal or no" depression, with score ranges of 10 to 18, 19 to 29, and 30 to 63 reflect "mild to moderate," "moderate to severe," and "severe" depression, respectively.

  Baseline, 3 Months, 6 Months, 9 Months, 12 Months

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

  This single-item self-assessed rating uses a 7-point rating scale with the options "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," and "very much worse."

  Baseline, 3 Months, 6 Months, 9 Months, 12 Months

Secondary Outcomes (12)

• Change in high sensitivity C-reactive protein

  Baseline, 6 months, 12 months

• Change in interleukin-8

  Baseline, 6 months, 12 months

• Change in tumor necrosis factor alpha

  Baseline, 6 months, 12 months

• Change in Tissue factor pathway inhibitor (TFPI)

  Baseline, 6 months, 12 months

• Change in von Willebrand factor antigen

  Baseline, 6 months, 12 months

Study Arms (2)

LNG IUD+ Norethindrone Acetate

EXPERIMENTAL

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

Drug: norethindrone acetate (NETA)

LNG IUD+Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

norethindrone acetate (NETA) DRUG

5mg of the NETA capsule by mouth daily for 12 months

Also known as: Aygestin

LNG IUD+ Norethindrone Acetate

Placebo DRUG

Placebo capsule everyday for 12 months

Also known as: gelatin capsules- filled with lactose monohydrate (0.2 gram)

LNG IUD+Placebo

Eligibility Criteria

• Age: 13 Years - 24 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Female with surgically confirmed endometriosis
• Clinical decision to begin use of the LNG-IUD
• Age 13 to 24 years
• Current pelvic pain (score ≥ 3 on Visual Analog Scale) that has been present for at least 2 months prior to enrollment
• Willingness to comply with visit schedule and study protocol

You may not qualify if:

• Pre-menarche or post-menopause
• Previous gonadotropin-releasing agonist use
• Contraindications to an IUD (e.g., cavity-distorting uterine anomaly, acute pelvic inflammatory disease, \<3 months from postpartum endometritis or septic abortion, local neoplasm, uterine bleeding of unknown etiology, breast cancer, untreated cervicitis or vaginitis or other lower genital tract infections)
• Active or historical venous thromboembolism, active or recent arterial thromboembolic disease
• Impaired liver function or liver disease
• Systemic lupus erythematosus
• Uncontrolled diabetes or uncontrolled hypertension (BPs \>140s/90s)
• Hypersensitivity to any component of the NETA or LNG-IUS
• Concurrent use of moderate or strong CYP34a inducers or inhibitors (such as erythromycin, ketoconazole, phenobarbital, rifampin)
• Significant mental or chronic systemic illnesses that may impact pain assessment
• Breast feeding, giving birth within the last 6 months, pregnancy, or planning to become pregnant in the next 12 month

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Endometriosis

Interventions

Norethindrone Acetate

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Norethindrone; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Amy DiVasta

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician, Division of Adolescent/Young Adult Medicine; Associate Professor of Pediatrics, Harvard Medical School

Model Details: Investigators will recruit 80 adolescents for participation in a double-blind, randomized trial of NETA (n=40) vs. placebo (control group, n=40) for adjunct treatment to the levonorgestrel-containing IUD for pelvic pain due to endometriosis.

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: July 2, 2021
• Study Start: January 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)