Effects of Anorexia Nervosa on Peak Bone Mass

NCT01301183 | Completed Phase 3 Results DMC

• 1 other identifier: 2010-P-002768
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anorexia Nervosa

Keywords

Anorexia Nervosa; Estrogen; Teenagers; IGF-1

Outcome Measures

Primary Outcomes (1)

• Change in Bone Density Over a 12-month Period

  Change in lumbar spine BMD z-score over 12 months as assessed by dual energy x-ray absorptiometry (DXA) The z-score indicates the number of standard deviations that BMD is away from the mean for age, sex and race. A z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher values. A positive change in z-scores indicates a favorable outcome whereas a negative change in z-scores indicates an unfavorable outcome.

  12 months

Secondary Outcomes (1)

• Change in Trabecular Number at the Ultradistal Radius Over a 12-month Period

  12 months

Study Arms (2)

Rh IGF-1 + Transdermal estradiol

EXPERIMENTAL

RhIGF-1 with transdermal 17-beta estradiol

Drug: RhIGF-1 with transdermal 17-beta estradiol

Placebo + Transdermal estradiol

PLACEBO COMPARATOR

Placebo and transdermal 17-beta estradiol

Drug: Placebo and transdermal 17-beta estradiol

Interventions

RhIGF-1 with transdermal 17-beta estradiol DRUG

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.

Also known as: Mecasermin and Vivelle Dot patch

Rh IGF-1 + Transdermal estradiol

Placebo and transdermal 17-beta estradiol DRUG

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.

Also known as: Vivelle Dot patch

Placebo + Transdermal estradiol

Eligibility Criteria

• Age: 14 Years - 22 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Anorexia Nervosa

Interventions

mecasermin

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders

Results Point of Contact

• Title: Madhu Misra
• Organization: Massachusetts General Hospital

mmisra@mgh.harvard.edu

6177265790

Study Officials

• Madhusmita Misra, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fritz Bradley Talbot and Nathan Bill Talbot Professor of Pediatrics

Study Record Dates

• First Submitted: February 18, 2011
• First Posted: February 23, 2011
• Study Start: February 1, 2011
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2020
• Last Updated: July 13, 2021
• Results First Posted: July 13, 2021

Record last verified: 2021-06

Locations

US (1)