The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial

Endometriosis Clinical Trial

Official title:

The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00474851
• Other study ID #: 07-01-0004
• Status: Completed
• Phase: Phase 2
• First received: May 15, 2007
• Last updated: March 17, 2015
• Start date: August 2007
• Est. completion date: January 2015

Study information

• Verified date: March 2015
• Source: Children's Hospital Boston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether a regimen of norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens is superior in maintaining skeletal health and quality of life in adolescents treated with a GnRH agonist for endometriosis.

Description:

Endometriosis has become increasingly recognized as a chronic illness which begins during adolescence. Untreated endometriosis may lead to chronic pain and infertility. As recognition of the need for prompt therapy increases, so does the length of time patients will be exposed to treatments. As a result, there exists a pressing need to evaluate adjunctive measures that may limit the associated negative health consequences of treatment.

A gonadotropin-releasing hormone (GnRH) agonist is one medication utilized for patients who have failed other treatments. While GnRH-agonists are effective in relieving symptoms, their long-term use is problematic. GnRH agonists induce a low-estrogen state, causing deleterious effects on bone mineralization. These negative consequences are especially important for our pediatric patients. Adolescence is the critical period in a woman's life for bone acquisition and attainment of peak bone mass. Anything that interferes with this process puts patients at risk for lifelong low bone density and future fracture.

"Add-back" therapy appears to be a promising adjunct to treatment for prevention of this bone loss. Daily therapy with low-doses of hormones preserves bone density in adult patients, without altering the efficacy of the GnRH-agonist. However, no data exist on the effect of add-back therapy in adolescents.

The aim of the current study is to evaluate the safety and efficacy of two add-back regimens, norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens, for the preservation of skeletal health and quality of life in adolescents with endometriosis treated with a GnRH-agonist.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: January 2015
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 13 Years to 22 Years

Eligibility

Inclusion Criteria:

• Age 13-22 years, at least two years post-menarche

• Body mass index (BMI, kg/m2) between 18 -30 kg/m2

• Surgical diagnosis of endometriosis

• Clinical decision to treat with a GnRH agonist, leuprolide depot (Lupron Depot®; TAP Pharmaceuticals, Inc.) 11.25 mg intra-muscular every 3 months

Exclusion Criteria:

• Concomitant chronic diseases which affect bone health, such as cystic fibrosis, inflammatory bowel disease, renal disease, or diabetes mellitus

• Markedly impaired liver function or liver failure

• Personal history of thromboembolic event (such as deep venous thrombosis)

• Medication use known to affect bone metabolism:

• Glucocorticoid therapy (including inhaled steroids) or anticonvulsants used in the last 6 months

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometriosis

Intervention

Drug:
• Norethindrone acetate + estrogens
Norethindrone acetate 5 mg by mouth daily + Conjugated equine estrogens 0.625 mg by mouth daily
• norethindrone acetate + placebo
norethindrone acetate 5 mg by mouth daily + Placebo capsule 1 pill by mouth daily

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Boston	Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone Mineral Density	Adjusted mean change in total body areal bone mineral density (aBMD) over the 12 month trial	Baseline to 12 months	Yes
Secondary	Total Body Bone Mineral Content (BMC)		Baseline to 12 months	No