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

This study has been completed.
Sponsor:
Collaborator:
Brigham and Women's Hospital
Information provided by (Responsible Party):
Amy DiVasta, Children's Hospital Boston
ClinicalTrials.gov Identifier:
NCT00474851
First received: May 15, 2007
Last updated: March 17, 2015
Last verified: March 2015

May 15, 2007
March 17, 2015
August 2007
October 2013   (final data collection date for primary outcome measure)
Bone Mineral Density [ Time Frame: Baseline to 12 months ] [ Designated as safety issue: Yes ]
Adjusted mean change in total body areal bone mineral density (aBMD) over the 12 month trial
Bone mineral density [ Time Frame: 12 months ]
Complete list of historical versions of study NCT00474851 on ClinicalTrials.gov Archive Site
Total Body Bone Mineral Content (BMC) [ Time Frame: Baseline to 12 months ] [ Designated as safety issue: No ]
  • Volumetric bone mineral density [ Time Frame: 12 months ]
  • Quality of life [ Time Frame: 12 months ]
Not Provided
Not Provided
 
The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial
The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Endometriosis
  • Drug: Norethindrone acetate + estrogens
    Norethindrone acetate 5 mg by mouth daily + Conjugated equine estrogens 0.625 mg by mouth daily
    Other Names:
    • Aygestin
    • Premarin
  • Drug: norethindrone acetate + placebo
    norethindrone acetate 5 mg by mouth daily + Placebo capsule 1 pill by mouth daily
    Other Name: Aygestin
  • Experimental: Norethindrone acetate + estrogens
    Subjects randomized to the experimental arm received add-back therapy with norethindrone acetate 5 mg by mouth daily + conjugated equine estrogens 0.625 mg by mouth daily for the 12 months of study participation.
    Intervention: Drug: Norethindrone acetate + estrogens
  • Placebo Comparator: norethindrone acetate + placebo
    Subjects randomized to the experimental arm received add-back therapy with norethindrone acetate 5 mg by mouth daily + a placebo capsule by mouth daily for the 12 months of study participation.
    Intervention: Drug: norethindrone acetate + placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
53
January 2015
October 2013   (final data collection date for primary outcome measure)

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
Female
13 Years to 22 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00474851
07-01-0004
Yes
Amy DiVasta, Children's Hospital Boston
Children's Hospital Boston
Brigham and Women's Hospital
Principal Investigator: Amy D DiVasta, MD, MMSc Children's Hospital Boston
Children's Hospital Boston
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP