| Conditions: |
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Anorexia Nervosa |
| Purpose: |
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Teenage girls with anorexia nervosa (AN) are at risk for low bone density and low rates of
bone accrual, raising concerns regarding acquisition of peak bone mass, an important
determinant of future bone health and fracture risk. Important factors contributing to low
bone density in AN include low levels of estrogen and insulin like growth factor-1 (IGF-1).
While estrogen is important for preventing bone loss, IGF-1 is important for optimizing bone
formation. We have shown in a previous study that replacement of estrogen is effective in
increasing bone density in teenage girls with AN; however, this increase in bone density
remains lower than that seen in normal-weight controls over the same duration, and residual
deficits persist. Importantly, the impact of administering replacement doses of IGF-1 with
estrogen replacement has not been studied in teenagers with AN.
This study will examine the impact of administering recombinant human (rh) insulin like
growth factor-1 (rhIGF-1) with estrogen (to mimic pubertal levels of these hormones) versus
administration of estrogen alone on bone metabolism in adolescent girls with anorexia
nervosa (AN).
One aim of this proposal is to investigate whether co-administration of insulin like growth
factor-1 (rhIGF-1) with physiologic estradiol replacement to adolescent girls with AN will
increase BMD (bone mineral density) more than estrogen monotherapy, and whether bone mass
will approach that seen in healthy adolescent girls. An additional aim is to determine
whether co-administration of rhIGF-1 with estradiol to mimic the normal pubertal milieu
stimulates bone formation through an IGF-1 mediated anabolic effect, increases bone density
to a greater extent than estrogen monotherapy, and improves bone mass accrual to approach
that in healthy controls. The impact of rhIGF-1 +estradiol versus estradiol alone on bone
microarchitecture will also be assessed.
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| Study Summary: |
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Given the increasing prevalence of AN, its profound consequences on bone health, and lack of
optimal treatment interventions, these studies will provide critical data needed to identify
optimal treatment strategies for this severe co-morbid disease using state- of- the- art
endpoints of BMD, bone microarchitecture and strength. Although both low IGF-1 and
hypogonadism are associated with increased skeletal fragility in AN, the mechanisms by which
these factors interact are incompletely understood. Specifically, the increased skeletal
fragility that is associated with AN is poorly reflected by DXA-derived BMD. Furthermore,
the magnitude and mechanisms by which IGF-1 deficiency and hypogonadism influence bone
microarchitecture are not defined. The growing incidence of eating disorders in adolescent
girls and their long-term effects on skeletal health provide strong rationale for studies
that will provide a better understanding of these issues and the evaluation of rational
therapeutic approaches. The studies described in this proposal utilize both cross-sectional
and RCT approaches to achieve this goal. Additionally, our utilization of sophisticated
techniques such as high resolution peripheral QCT (HR-pQCT) will improve our understanding
of the relationship between IGF-1, gonadal steroids and bone quality and will aid in the
development of effective therapies in the treatment of skeletal fragility in Anorexia
Nervosa.
|
| Criteria: |
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Inclusion Criteria: AN:
- Age: 14-21 years old
- Bone age (BA): ≥15 years
- Should meet DSM IV criteria for AN
- Subjects at MGH will be evaluated by co-investigator Dr. David Herzog, Director of
the Harris Center for Eating Disorders, at MGH, and by Dr. Debra Katzman,
co-investigator, and the Hospital for Sick Children, Toronto who directs their Eating
Disorders Program, respectively, before enrollment.
Inclusion Criteria: Controls:
- Healthy adolescent girls 14-21 years
- BA of ≥15 years
- BMI between the 10th-90th percentiles for age
- Regular menstrual periods every 28-35 days for subjects ≥ 2 years post-menarche.
Exclusion Criteria:
- Diseases known to affect bone metabolism including untreated thyroid disease,
Cushing's syndrome, diabetes, pituitary disease, renal failure and prior bone
fracture within six months of the study.
- Medications known to affect bone metabolism, including gonadal steroids, within three
months.
- Evidence of suicidality, psychosis, or substance abuse.
- Premature ovarian failure, as demonstrated by an elevated FSH.
- Abnormal TSH.
- Hematocrit <30%, Potassium <3.0 mmol/L, Glucose <50 mg/dl
- Pregnancy
- History of malignancy
- Contraindications to estrogen therapy (for girls with AN)
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| NCT ID: |
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NCT01301183 |
| Primary Contact: |
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Principal Investigator
Anne Klibanski, MD
Massachusetts General Hospital
Nara Mendes Estella, BA
Phone: 617-724-6046
Email: nmendesestella@partners.org
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| Backup Contact: |
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Email: mmisra@partners.org
Madhu Misra, MD, MPH
Phone: 617-724-5602
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| Location Contact: |
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Boston, Massachusetts 02114
United States
Nara Estella, BA
Phone: 617-724-6046
Email: nmendesestella@partners.org
Site Status: Recruiting |