Adrenal and Gonadal Hormone Replacement in Anorexia Nervosa

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Catherine M. Gordon, Children's Hospital Boston
ClinicalTrials.gov Identifier:
NCT00310791
First received: April 3, 2006
Last updated: December 27, 2012
Last verified: December 2012
  Purpose

This study seeks to gain new information on why young women with anorexia nervosa are predisposed to early bone loss and osteoporosis. Through a randomized treatment trial in which participants will receive either combined therapy with the adrenal hormone, dehydroepiandrosterone (DHEA) and estrogen replacement therapy or placebo, we will determine the effects of an 18-month treatment course on bone mass, circulating markers of bone turnover, and serum levels of a factor, insulin-like growth factor I (IGF-I). We are also studying if these therapies change bone structure to increase skeletal strength compared to placebo, as assessed through cross-sectional geometric analysis of our bone density data by dual-energy x-ray absorptiometry (DXA).


Condition Intervention Phase
Anorexia Nervosa
Drug: Hormone replacement therapy (estrogen/progestin)
Other: Placebo (Sugar Pill)
Drug: Dehydroepiandrosterone (DHEA)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Adrenal and Gonadal Hormone Replacement in Young Women With Anorexia Nervosa

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Areal Bone Density by DXA [ Time Frame: 18-Months ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: April 2004
Study Completion Date: December 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar Pill
Placebo (sugar pill); identical to treatment medication capsule
Other: Placebo (Sugar Pill)
Placebo (sugar pill)
Other Names:
  • Placebo
  • Sugar pill
Experimental: DHEA + Hormone replacement therapy (estrogen/progestin)
Combined therapy of dehydroepiandrosterone (DHEA) and hormone replacement therapy (ERT). Patients randomized to the DHEA + HRT arm will receive micronized oral DHEA in a dose of 50 mg daily + HRT (0.3 mg Premarin, 1 tablet daily for 3 months, follow by Alesse (20 mg ethinyl estradiol + 0.1 mg levonorgestrel for 15 months). The estrogen/progestin component of the regimen has been chosen to maximize patient compliance, as patients with AN may experience bloating or nausea if higher estrogen doses (> 20 g) are initiated too rapidly. The DHEA capsule strength will be 50 mg, the total daily dose to be studied in combination with HRT. The micronized DHEA preparation achieves more constant DHEA and DHEA-S levels. Fifty milligrams appears to be a physiological replacement dose for these young women, determined both from our pilot (10) and longitudinal studies (7).
Drug: Hormone replacement therapy (estrogen/progestin)
Hormone replacement therapy (estrogen/progestin). 0.3 mg conjugated estrogens x 3 months, followed by 9 months of oral contraceptive (20 mg ethinyl estradiol + 0.1 mg levonorgestrel)
Other Names:
  • Alesse (20 mg ethinyl estradiol + 0.1 mg levonorgestrel)
  • Premarin (conjugated estrogens)
Drug: Dehydroepiandrosterone (DHEA)
50 mg tablet, 1 daily
Other Name: Prasterone

Detailed Description:

Profound osteopenia is a frequent and often irreversible complication of anorexia nervosa (AN). Adolescents with AN often have a reduced peak bone mass and are at increased risk for early osteoporosis and fractures. These young women have subnormal serum levels of gonadal steroids and the adrenal androgen dehydroepiandrosterone (DHEA) that may be associated with their low bone mineral density (BMD). Low DHEA levels are accompanied by decreased levels of insulin-like growth factor I (IGF-I), estrogen, and testosterone. Previous data from our group indicate that oral DHEA therapy in young women with AN: increases lean body mass, serum levels of bone formation markers and insulin-like growth factor I (IGF-I), and decreases urinary markers of bone resorption. We also found that standard hormonal replacement therapy (HRT) significantly decreased bone resorption markers. Information on the effects of these therapies on bone strength and ultimate fracture risk is lacking.

In this project, we will test the hypothesis that combined therapy with DHEA and estrogen/progestin will enhance bone mass in patients with AN through anabolic and antiosteolytic mechanisms. We will test the hypothesis that 18 months of DHEA + HRT will increase bone mineral density (BMD) and markers of bone formation, while decreasing bone resorption markers in these patients. The proposed study will examine whether restoring normal levels of DHEA and estrogen in these young women will increase bone mass during a critical period for bone accretion. The study will also examine whether DHEA's anabolic effects on bone are mediated through the skeletal IGF-I regulatory system. Using cross-sectional analyses of dual energy x-ray absorptiometry (DXA) data, we will also measure indices of bone structural geometry to determine if mechanical strength is compromised in these young women, and if strength is restored in response to combined anabolic/antiresorptive therapy.

To gain new information on the mechanisms underlying bone loss and fracture risk in young women with AN, our research goals are:

Specific Aim I: Through a randomized controlled trial, to measure the effects of an 18-month course of DHEA + HRT on bone mass, markers of bone turnover, and serum levels of IGF-I compared to placebo. Specific Aim II: To determine whether combined therapy with adrenal and gonadal steroid replacement changes bone structure to increase strength compared to placebo, as assessed through cross-sectional geometric analysis of DXA data.

  Eligibility

Ages Eligible for Study:   15 Years to 30 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 15 - 30 years
  • Anorexia nervosa by psychiatric criteria
  • Amenorrhea for at least 3 months

Exclusion Criteria:

  • Receiving no medications known to affects bone metabolism
  • No other chronic medical conditions
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00310791

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Children's Hospital Boston
Investigators
Principal Investigator: Catherine M. Gordon, MD Children's Hospital Boston
  More Information

No publications provided by Children's Hospital Boston

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Catherine M. Gordon, Catherine Gordon, MD, MSc, Children's Hospital Boston
ClinicalTrials.gov Identifier: NCT00310791     History of Changes
Other Study ID Numbers: Anorexia04, RO1 HD043869
Study First Received: April 3, 2006
Results First Received: June 22, 2011
Last Updated: December 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Boston:
anorexia nervosa
adolescents
dual-energy x-ray absorptiometry
dehydroepiandrosterone (DHEA)
osteoporosis

Additional relevant MeSH terms:
Anorexia
Anorexia Nervosa
Signs and Symptoms, Digestive
Signs and Symptoms
Eating Disorders
Mental Disorders
Contraceptives, Oral
Levonorgestrel
Dehydroepiandrosterone
Estradiol
Estrogens, Conjugated (USP)
Estrogens
Ethinyl Estradiol
Hormones
Progestins
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Adjuvants, Immunologic
Immunologic Factors
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptives, Oral, Synthetic

ClinicalTrials.gov processed this record on April 17, 2014