Effects of Anorexia Nervosa on Bone Mass in Adolescents

This study has been completed.
Sponsor:
Collaborators:
The Hospital for Sick Children
Information provided by (Responsible Party):
Anne Klibanski, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00088153
First received: July 20, 2004
Last updated: October 6, 2011
Last verified: September 2011
  Purpose

This study is to determine the effects of anorexia nervosa on bone mass and hormone levels in adolescents. Whether administration of estrogen, a normal hormone present during puberty, can help maintain bone development in girls with anorexia nervosa will be determined.


Condition Intervention Phase
Anorexia Nervosa
Drug: Physiologic Estrogen/progesterone
Other: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Anorexia Nervosa on Peak Bone Mass

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Percent Change in Spine Bone Density Over the Study Duration (18 Months) [ Time Frame: Baseline and 18 months ] [ Designated as safety issue: No ]

    Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months.

    The primary outcome was the percent change in bone density at the spine from baseline to 18 months. Areal bone density is measured as g/cm2. The unit of measure for the percent change in bone density is 'percent' Percent change in bone density= [[Bone density at 18 months- Bone density at baseline)*100/Bone density at baseline]%


  • Change in Spine Bone Mineral Density Z-scores Over the Study Duration (18 Months) [ Time Frame: Baseline and 18 months ] [ Designated as safety issue: No ]

    Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months.

    The other primary outcome was the change in spine bone density Z-score from baseline to 18 months. The bone density Z-score is a standard deviation score that compares one's bone density to the mean for age and gender, and the Z-score, therefore, does not have any units. It is simply referred to as a Z-score. Change in bone density Z-score= [Bone density Z-score at 18 months- Bone density Z-score at baseline]



Secondary Outcome Measures:
  • Change in N-terminal Propeptide of Type 1 Procollagen (P1NP) Over the Study Duration (18 Months) [ Time Frame: Baseline and 18 months ] [ Designated as safety issue: No ]

    P1NP is a surrogate marker of bone formation that is measured in serum. P1NP levels were measured at baseline, 6, 12 and 18 months.

    A secondary outcome was the change in P1NP levels from baseline to 18 months: [P1NP at 18 months - P1NP at baseline). The unit is ng/ml



Enrollment: 110
Study Start Date: July 2003
Study Completion Date: June 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Physiologic estrogen replacement

Mature girls with anorexia nervosa (AN) (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month).

Immature girls with AN (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study

Drug: Physiologic Estrogen/progesterone
Vivelle Dot patch 100 mcg twice weekly; Provera 2.5 mg daily for the first 10 days of the month
Other Name: Bone age >=15: Vivelle Dot patch with cyclic Provera
Placebo Comparator: Placebo
Placebo patches or pills
Other: Placebo
Placebo patches twice weekly; Placebo pills daily for the first 10 days of every month

Detailed Description:

Adolescence is a critical time for bone mineral accretion as between 60-90% of peak bone mass is established during this period, and peak bone mass is a major determinant of bone density and osteoporosis risk during adulthood. Anorexia nervosa (AN) is the third most common chronic illness among adolescent girls, with a prevalence of 0.2-1.0%. Therefore, AN occurs at a time during which patients are the most vulnerable to disruption of bone mineral accretion. Osteopenia is a major co-morbid complication of AN in 50-75% of female adolescents and adult women with this eating disorder. Women with the onset of the disorder during adolescence have more severe osteopenia than women with onset during adulthood. Little is known about the pathogenesis of osteopenia in this adolescent population and there are no established therapies. Improved understanding of bone mineral metabolism and factors which predict recovery of bone mineral accretion are critical in the development of therapeutic strategies to preserve and maximize bone mass in girls with the onset of AN during adolescence. Estrogen is known to be a critical factor in the development of peak bone mass. Although AN is associated with profound estrogen deficiency, there are no controlled studies investigating the effects of estrogen administration in this population.

This research proposal will address critical unanswered questions regarding bone abnormalities in adolescents with anorexia nervosa. Defining changes in bone formation with weight recuperation and hormonal variables would provide insight into the factors essential for bone mineral accretion during adolescence, as well as those that predict recovery. Determination of dose-dependent estrogen effects in this population will be key in targeting interventions during the time of active disease, with the long-term goal of preserving peak bone mass accretion in this vulnerable group of patients. Data obtained from women with post-menopausal osteoporosis or from women with AN cannot be extrapolated to adolescent patients who are in an active period of bone growth and mineralization as well as remodeling. Given the increasing prevalence of AN and its profound consequences on bone health, these studies will provide much needed data to enable treatment strategies for this severe co-morbid disease.

  Eligibility

Ages Eligible for Study:   12 Years to 18 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Females Only with Anorexia Nervosa and Amenorrhea 12-18 years
  • Normal-weight girls 12-18 years with no past or present history of an eating disorder

Exclusion Criteria:

  • Diseases affecting bone metabolism (including untreated thyroid disease, premature ovarian failure, diabetes, cancer, pituitary, renal disease or bone fracture within the past six months)
  • Use of prescription medications affecting bone metabolism within three months
  • Suicidality
  • Psychosis
  • Substance abuse
  • Hematocrit <30 %
  • Potassium <3.0 mmol/L
  • Glucose <50 mg/dl.
  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: NCT00088153

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
The Hospital for Sick Children
Investigators
Principal Investigator: Anne Klibanski, MD Massachusetts General Hospital
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anne Klibanski, MD, Laurie Carrol Guthart Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00088153     History of Changes
Other Study ID Numbers: DK062249, R01DK062249
Study First Received: July 20, 2004
Results First Received: July 6, 2011
Last Updated: October 6, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Anorexia Nervosa
Amenorrhea
Bone Mass
Growth hormone

Additional relevant MeSH terms:
Anorexia
Anorexia Nervosa
Signs and Symptoms, Digestive
Signs and Symptoms
Eating Disorders
Mental Disorders
Estrogens
Progesterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Progestins

ClinicalTrials.gov processed this record on August 21, 2014