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Effects of Anorexia Nervosa on Peak Bone Mass

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Massachusetts General Hospital
Sponsor:
Collaborator:
The Hospital for Sick Children
Information provided by (Responsible Party):
Anne Klibanski, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01301183
First received: February 18, 2011
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Anorexia Nervosa
Drug: RhIGF-1 with transdermal 17-beta estradiol
Drug: Placebo and transdermal 17-beta estradiol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
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:
  • A significant increase in bone density over a 12-month period [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • A significant improvement in bone microarchitecture parameters at the ultradistal radius and tibia over a 12-month period [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 136
Study Start Date: February 2011
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rh IGF-1 + Transdermal estradiol
RhIGF-1 with transdermal 17-beta estradiol
Drug: RhIGF-1 with transdermal 17-beta estradiol

RhIGF-1 will be started at a dose of 30mcg/k/dose twice daily, and will be titrated up or down in 25% dose increments to maintain IGF-1 levels in the upper half of the normal range.

Estradiol will be delivered transdermally using a 100 mcg patch (Vivelle Dot) changed twice weekly. Subjects will receive cyclic micronized progesterone (Prometrium) 100 mg daily for the first 10 days of each month. All subjects will receive supplemental calcium and vitamin D.

Other Name: Mecasermin and Vivelle Dot patch
Placebo Comparator: Placebo + Transdermal estradiol
Placebo and transdermal 17-beta estradiol
Drug: Placebo and transdermal 17-beta estradiol
Placebo injections will be administered twice daily. Estradiol will be delivered transdermally using a patch (100 mcg) changed twice weekly. Subjects will receive cyclic micronized progesterone (Prometrium) 100 mg daily for the first 10 days of each month. All subjects will receive supplemental calcium and vitamin D.
Other Name: Vivelle Dot patch

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   14 Years to 22 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria: AN:

  • Age: 14-22 years old
  • Bone age (BA): ≥14 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 14-22 years
  • BA of ≥14 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)
  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: NCT01301183

Contacts
Contact: Amelia Mostovoy, BA 617-643-0266 AMOSTOVOY@PARTNERS.ORG
Contact: Madhu Misra, MD, MPH 617-724-5602 mmisra@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Amelia Mostovoy, BA    617-643-0266    AMOSTOVOY@PARTNERS.ORG   
Contact: Madhusmita Misra, MD    617-726-3870    mmisra@partners.org   
Principal Investigator: Anne Klibanski, MD         
Canada, Ontario
The Hospital for Sick Children Not yet recruiting
Toronto, Ontario, Canada
Contact: Debra Katzman, MD       debra.katzman@sickkids.ca   
Sub-Investigator: Debra Katzman, MD         
Sponsors and Collaborators
Massachusetts General Hospital
The Hospital for Sick Children
Investigators
Principal Investigator: Anne Klibanski, MD Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Anne Klibanski, MD, Laurie Carrol Guthart Professor of Medicine Associate Dean for Clinical and Translational Research, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01301183     History of Changes
Other Study ID Numbers: 2010-P-002768
Study First Received: February 18, 2011
Last Updated: October 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Anorexia Nervosa
Estrogen
Teenagers
IGF-1

Additional relevant MeSH terms:
Anorexia
Anorexia Nervosa
Eating Disorders
Mental Disorders
Signs and Symptoms
Signs and Symptoms, Digestive
Estradiol
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estradiol valerate
Polyestradiol phosphate
Contraceptive Agents
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014