Anorexia NervosaPhase 3NCT01301183
Effects of Anorexia Nervosa on Peak Bone Mass
A Phase 3 study testing RhIGF-1 with transdermal 17-beta estradiol in people with Anorexia Nervosa, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 14 to 22 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Anorexia Nervosa
- What is being tested?
- RhIGF-1 with transdermal 17-beta estradiol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Mar 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 22 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- Pregnancy
- History of malignancy
- Contraindications to estrogen therapy (for girls with AN)
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
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.
Read the 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.
- Conditions
- Anorexia Nervosa
- Being tested
- RhIGF-1 with transdermal 17-beta estradiol, Placebo and transdermal 17-beta estradiol
- Keywords
- Anorexia Nervosa, Estrogen, Teenagers, IGF-1
- Medical subject headings
- Anorexia Nervosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RhIGF-1 with transdermal 17-beta estradiolDrug
Also called Mecasermin and Vivelle Dot patch
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.
Placebo and transdermal 17-beta estradiolDrug
Also called Vivelle Dot patch
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.
| Study group | Role | What they receive |
|---|---|---|
| Rh IGF-1 + Transdermal estradiol | Experimental | RhIGF-1 with transdermal 17-beta estradiol Receives: Drug: RhIGF-1 with transdermal 17-beta estradiol |
| Placebo + Transdermal estradiol | Placebo comparator | Placebo and transdermal 17-beta estradiol Receives: Drug: Placebo and transdermal 17-beta estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (1)
Change in Trabecular Number at the Ultradistal Radius Over a 12-month Period
Change in trabecular number at the ultradistal radius over 12 months as assessed by high resolution peripheral quantitative computed tomography (HRpQCT)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2011 (estimated)
- Study startFeb 2011
- Primary completionMar 2019
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anorexia NervosaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Madhusmita Misra, Massachusetts General Hospital
- Investigators
- Madhusmita Misra, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01301183
- Sponsor's protocol ID
- 2010-P-002768
- Status last verified
- Jun 2021
- First submitted
- 18 Feb 2011
- Last updated
- 13 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Anorexia Nervosa on Peak Bone Mass
- ClinicalTrials.gov ID
- NCT01301183
- Acronym / sponsor ID
- 2010-P-002768
- Conditions
- Anorexia Nervosa
- Keywords
- Anorexia Nervosa, Estrogen, Teenagers, IGF-1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Feb 2011 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 23 Feb 2011 (estimated)
- Results
- Posted 13 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rh IGF-1 + Transdermal estradiol | Experimental | Drug: RhIGF-1 with transdermal 17-beta estradiolRhIGF-1 with transdermal 17-beta estradiol |
| Placebo + Transdermal estradiol | Placebo comparator | Drug: Placebo and transdermal 17-beta estradiolPlacebo and transdermal 17-beta estradiol |
Who may qualify
- Ages
- 14 to 22 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RhIGF-1 with transdermal 17-beta estradiolAlso: Mecasermin and Vivelle Dot patchRhIGF-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. | Drug | Rh IGF-1 + Transdermal estradiol |
| Placebo and transdermal 17-beta estradiolAlso: Vivelle Dot patchPlacebo 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. | Drug | Placebo + Transdermal estradiol |
Primary outcome
Change in Bone Density Over a 12-month Period
Time frame: 12 months
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.
1 secondary outcome
Change in Trabecular Number at the Ultradistal Radius Over a 12-month Period
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Madhusmita Misra, MD, MPH principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RhIGF-1 with transdermal 17-beta estradiol in people with Anorexia Nervosa, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Bone Density Over a 12-month Period (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2021.