Trial · Interventional

CompletedPhase 3Results postedRegistry data

Effects of Anorexia Nervosa on Peak Bone Mass

NCTNCT01301183Other id2010-P-002768

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 75 participants (actual)
Sponsor: Massachusetts General Hospital · Other
Design: Randomized · Double masking
Countries: 1 country
United States
Start: Feb 2011
Primary completion: Mar 2019
Completion: Mar 2020
First posted: 23 Feb 2011 (estimated)
Last update posted: 13 Jul 2021
Conditions: Anorexia Nervosa

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

20122014201620182020

Ph 3
Effects of Anorexia Nervosa on Peak Bone Mass
NCT01301183
Feb 2011 to Mar 2020

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

RhIGF-1 with transdermal 17-beta estradiolDrug
Placebo and transdermal 17-beta estradiolDrug

Arms2

Experimental
Rh IGF-1 + Transdermal estradiol
RhIGF-1 with transdermal 17-beta estradiol
Placebo comparator
Placebo + Transdermal estradiol
Placebo and transdermal 17-beta estradiol

Primary outcomes1

Outcomes the sponsor listed as primary.

Change in Bone Density Over a 12-month Period
Time frame · 12 months
Registry description
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.

Secondary outcomes(1)

Change in Trabecular Number at the Ultradistal Radius Over a 12-month Period
Time frame · 12 months
Registry description
Change in trabecular number at the ultradistal radius over 12 months as assessed by high resolution peripheral quantitative computed tomography (HRpQCT)

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMedian· 12 months

Change in Bone Density Over a 12-month Period

Group	Value (score on a scale)
Rh IGF-1 + Transdermal Estradiol	0.045
Placebo + Transdermal Estradiol	0.280

Secondary and other outcome results(1)

Secondary outcomeMedian· 12 months

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

Group	Value (1/mm)
Rh IGF-1 + Transdermal Estradiol	-0.10
Placebo + Transdermal Estradiol	-0.02

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Rh IGF-1 + Transdermal EstradiolRhIGF-1 with transdermal 17-beta estradiol 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.	0 / 38	7 / 38	8 / 38
Placebo + Transdermal EstradiolPlacebo and transdermal 17-beta estradiol 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.	0 / 37	12 / 37	19 / 37

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: Female
Age: from 14 Years up to 22 Years
Healthy volunteers: Accepted

Inclusion and exclusion criteria, as posted

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)

PepBank is a research reference. Talk to a doctor before you use any peptide.