Effects of Anorexia Nervosa on Peak Bone Mass
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.
|Anorexia Nervosa||Drug: RhIGF-1 with transdermal 17-beta estradiol Drug: Placebo and transdermal 17-beta estradiol||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Effects of Anorexia Nervosa on Peak Bone Mass|
- A significant increase in bone density over a 12-month period [ Time Frame: 12 months ]
- A significant improvement in bone microarchitecture parameters at the ultradistal radius and tibia over a 12-month period [ Time Frame: 12 months ]
|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)|
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01301183
|Contact: Shreya Tulsiani, BA||617-643-0266||STULSIANI@MGH.HARVARD.EDU|
|Contact: Madhu Misra, MD, MPHemail@example.com|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Shreya Tulsiani, BA 617-643-0266 firstname.lastname@example.org|
|Contact: Madhusmita Misra, MD 617-726-3870 email@example.com|
|Principal Investigator: Anne Klibanski, MD|
|Principal Investigator:||Anne Klibanski, MD||Massachusetts General Hospital|