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
  Purpose

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.


Condition Intervention Phase
Endometriosis
Drug: Norethindrone acetate + estrogens
Drug: norethindrone acetate + placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial

Resource links provided by NLM:


Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Total Body Bone Mineral Content (BMC) [ Time Frame: Baseline to 12 months ] [ Designated as safety issue: No ]

Enrollment: 53
Study Start Date: August 2007
Study Completion Date: January 2015
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Norethindrone acetate + estrogens
Norethindrone acetate 5 mg by mouth daily + Conjugated equine estrogens 0.625 mg by mouth daily
Other Names:
  • Aygestin
  • Premarin
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.
Drug: norethindrone acetate + placebo
norethindrone acetate 5 mg by mouth daily + Placebo capsule 1 pill by mouth daily
Other Name: Aygestin

Detailed 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.

  Eligibility

Ages Eligible for Study:   13 Years to 22 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00474851

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Children's Hospital Boston
Brigham and Women's Hospital
Investigators
Principal Investigator: Amy D DiVasta, MD, MMSc Children's Hospital Boston
  More Information

No publications provided

Responsible Party: Amy DiVasta, Principal Investigator, Children's Hospital Boston
ClinicalTrials.gov Identifier: NCT00474851     History of Changes
Other Study ID Numbers: 07-01-0004
Study First Received: May 15, 2007
Results First Received: March 4, 2015
Last Updated: March 17, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Boston:
Endometriosis
Adolescents
Bone density
GnRH Agonist
Add-back therapy

Additional relevant MeSH terms:
Endometriosis
Genital Diseases, Female
Deslorelin
Estrogens
Norethindrone
Norethindrone acetate
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015