Anorexia NervosaPhase 2/3NCT00088153
Effects of Anorexia Nervosa on Bone Mass in Adolescents
A Phase 2/3 study testing Physiologic Estrogen/progesterone in people with Anorexia Nervosa, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study is to determine the effects of anorexia nervosa on bone mass and hormone levels in adolescents. Whether administration of estrogen, a normal hormone present during puberty, can help maintain bone development in girls with anorexia nervosa will be determined. Read more about this study
- Who is it for?
- Ages 12 to 18 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Anorexia Nervosa
- What is being tested?
- Physiologic Estrogen/progesterone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2003to Jun 2011
- Phase
- Phase 2/3
- 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 12 to 18 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Females Only with Anorexia Nervosa and Amenorrhea 12-18 years
- Normal-weight girls 12-18 years with no past or present history of an eating disorder
Who cannot join
- Diseases affecting bone metabolism (including untreated thyroid disease, premature ovarian failure, diabetes, cancer, pituitary, renal disease or bone fracture within the past six months)
- Use of prescription medications affecting bone metabolism within three months
- Suicidality
- Psychosis
- Substance abuse
- Hematocrit <30 %
- Potassium <3.0 mmol/L
- Glucose <50 mg/dl.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Effects of Anorexia Nervosa on Peak Bone Mass
This study is to determine the effects of anorexia nervosa on bone mass and hormone levels in adolescents. Whether administration of estrogen, a normal hormone present during puberty, can help maintain bone development in girls with anorexia nervosa will be determined.
Read the detailed description
Adolescence is a critical time for bone mineral accretion as between 60-90% of peak bone mass is established during this period, and peak bone mass is a major determinant of bone density and osteoporosis risk during adulthood. Anorexia nervosa (AN) is the third most common chronic illness among adolescent girls, with a prevalence of 0.2-1.0%. Therefore, AN occurs at a time during which patients are the most vulnerable to disruption of bone mineral accretion. Osteopenia is a major co-morbid complication of AN in 50-75% of female adolescents and adult women with this eating disorder. Women with the onset of the disorder during adolescence have more severe osteopenia than women with onset during adulthood. Little is known about the pathogenesis of osteopenia in this adolescent population and there are no established therapies. Improved understanding of bone mineral metabolism and factors which predict recovery of bone mineral accretion are critical in the development of therapeutic strategies to preserve and maximize bone mass in girls with the onset of AN during adolescence. Estrogen is known to be a critical factor in the development of peak bone mass. Although AN is associated with profound estrogen deficiency, there are no controlled studies investigating the effects of estrogen administration in this population.
This research proposal will address critical unanswered questions regarding bone abnormalities in adolescents with anorexia nervosa. Defining changes in bone formation with weight recuperation and hormonal variables would provide insight into the factors essential for bone mineral accretion during adolescence, as well as those that predict recovery. Determination of dose-dependent estrogen effects in this population will be key in targeting interventions during the time of active disease, with the long-term goal of preserving peak bone mass accretion in this vulnerable group of patients. Data obtained from women with post-menopausal osteoporosis or from women with AN cannot be extrapolated to adolescent patients who are in an active period of bone growth and mineralization as well as remodeling. Given the increasing prevalence of AN and its profound consequences on bone health, these studies will provide much needed data to enable treatment strategies for this severe co-morbid disease.
- Conditions
- Anorexia Nervosa
- Being tested
- Physiologic Estrogen/progesterone, Placebo
- Keywords
- Anorexia Nervosa, Amenorrhea, Bone Mass, Growth hormone
- Medical subject headings
- Anorexia Nervosa, Amenorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physiologic Estrogen/progesteroneDrug
Also called Bone age >=15: Vivelle Dot patch with cyclic Provera
Vivelle Dot patch 100 mcg twice weekly; Provera 2.5 mg daily for the first 10 days of the month
PlaceboOther
Placebo patches twice weekly; Placebo pills daily for the first 10 days of every month
| Study group | Role | What they receive |
|---|---|---|
| Physiologic estrogen replacement | Experimental | Mature girls with anorexia nervosa (AN) (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month).
Immature girls with AN (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study Receives: Drug: Physiologic Estrogen/progesterone |
| Placebo | Placebo comparator | Placebo patches or pills Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Spine Bone Density Over the Study Duration (18 Months)
Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months.
The primary outcome was the percent change in bone density at the spine from baseline to 18 months. Areal bone density is measured as g/cm2. The unit of measure for the percent change in bone density is 'percent' Percent change in bone density= [[Bone density at 18 months- Bone density at baseline)*100/Bone density at baseline]%
Measured: Baseline and 18 months
Change in Spine Bone Mineral Density Z-scores Over the Study Duration (18 Months)
Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months.
The other primary outcome was the change in spine bone density Z-score from baseline to 18 months. The bone density Z-score is a standard deviation score that compares one's bone density to the mean for age and gender, and the Z-score, therefore, does not have any units. It is simply referred to as a Z-score. Change in bone density Z-score= [Bone density Z-score at 18 months- Bone density Z-score at baseline]
Measured: Baseline and 18 months
Secondary outcomes (1)
Change in N-terminal Propeptide of Type 1 Procollagen (P1NP) Over the Study Duration (18 Months)
P1NP is a surrogate marker of bone formation that is measured in serum. P1NP levels were measured at baseline, 6, 12 and 18 months.
A secondary outcome was the change in P1NP levels from baseline to 18 months: [P1NP at 18 months - P1NP at baseline). The unit is ng/ml
Measured: Baseline and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2004 (estimated)
- Study startJul 2003
- Primary completionFeb 2011
- Study completionJun 2011
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.
- Publications (3)Papers the sponsor has linked to this study.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The Hospital for Sick Children
- Responsible party
- Principal investigator, Madhusmita Misra, Massachusetts General Hospital
- Investigators
- Madhusmita Misra, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00088153
- Sponsor's protocol ID
- DK062249
- Other IDs
- R01DK062249
- Status last verified
- Oct 2021
- First submitted
- 20 Jul 2004
- Last updated
- 2 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Misra M, Katzman D, Miller KK, Mendes N, Snelgrove D, Russell M, Goldstein MA, Ebrahimi S, Clauss L, Weigel T, Mickley D, Schoenfeld DA, Herzog DB, Klibanski A. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J Bone Miner Res. 2011 Oct;26(10):2430-8. doi: 10.1002/jbmr.447.
PubMed 21698665Misra M, Katzman DK, Estella NM, Eddy KT, Weigel T, Goldstein MA, Miller KK, Klibanski A. Impact of physiologic estrogen replacement on anxiety symptoms, body shape perception, and eating attitudes in adolescent girls with anorexia nervosa: data from a randomized controlled trial. J Clin Psychiatry. 2013 Aug;74(8):e765-71. doi: 10.4088/JCP.13m08365.
PubMed 24021517Faje AT, Fazeli PK, Katzman DK, Miller KK, Breggia A, Rosen CJ, Mendes N, Klibanski A, Misra M. Sclerostin levels and bone turnover markers in adolescents with anorexia nervosa and healthy adolescent girls. Bone. 2012 Sep;51(3):474-9. doi: 10.1016/j.bone.2012.06.006. Epub 2012 Jun 15.
PubMed 22728230
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 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
- NCT00088153
- Acronym / sponsor ID
- DK062249
- Conditions
- Anorexia Nervosa
- Keywords
- Anorexia Nervosa, Amenorrhea, Bone Mass, Growth hormone
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), The Hospital for Sick Children
- Study start
- Jul 2003
- Primary completion
- Feb 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 21 Jul 2004 (estimated)
- Results
- Posted 10 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to determine the effects of anorexia nervosa on bone mass and hormone levels in adolescents. Whether administration of estrogen, a normal hormone present during puberty, can help maintain bone development in girls with anorexia nervosa will be determined.
Detailed description
Adolescence is a critical time for bone mineral accretion as between 60-90% of peak bone mass is established during this period, and peak bone mass is a major determinant of bone density and osteoporosis risk during adulthood. Anorexia nervosa (AN) is the third most common chronic illness among adolescent girls, with a prevalence of 0.2-1.0%. Therefore, AN occurs at a time during which patients are the most vulnerable to disruption of bone mineral accretion. Osteopenia is a major co-morbid complication of AN in 50-75% of female adolescents and adult women with this eating disorder. Women with the onset of the disorder during adolescence have more severe osteopenia than women with onset during adulthood. Little is known about the pathogenesis of osteopenia in this adolescent population and there are no established therapies. Improved understanding of bone mineral metabolism and factors which predict recovery of bone mineral accretion are critical in the development of therapeutic strategies to preserve and maximize bone mass in girls with the onset of AN during adolescence. Estrogen is known to be a critical factor in the development of peak bone mass. Although AN is associated with profound estrogen deficiency, there are no controlled studies investigating the effects of estrogen administration in this population.
This research proposal will address critical unanswered questions regarding bone abnormalities in adolescents with anorexia nervosa. Defining changes in bone formation with weight recuperation and hormonal variables would provide insight into the factors essential for bone mineral accretion during adolescence, as well as those that predict recovery. Determination of dose-dependent estrogen effects in this population will be key in targeting interventions during the time of active disease, with the long-term goal of preserving peak bone mass accretion in this vulnerable group of patients. Data obtained from women with post-menopausal osteoporosis or from women with AN cannot be extrapolated to adolescent patients who are in an active period of bone growth and mineralization as well as remodeling. Given the increasing prevalence of AN and its profound consequences on bone health, these studies will provide much needed data to enable treatment strategies for this severe co-morbid disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Physiologic estrogen replacement | Experimental | Drug: Physiologic Estrogen/progesteroneMature girls with anorexia nervosa (AN) (bone age 15 or greater): Transdermal estradiol (100 mcg) with cyclic progesterone (days 1-10 of each month). Immature girls with AN (bone age less than 15 years): Ethinyl estradiol (3.75 mcg daily for the first 6 months, 7.5 mcg daily for the next 6 months, and 11.25 mcg daily for the final 6 months of the study |
| Placebo | Placebo comparator | Other: PlaceboPlacebo patches or pills |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Females Only with Anorexia Nervosa and Amenorrhea 12-18 years
- Normal-weight girls 12-18 years with no past or present history of an eating disorder
Key exclusion criteria (8 listed)
- Diseases affecting bone metabolism (including untreated thyroid disease, premature ovarian failure, diabetes, cancer, pituitary, renal disease or bone fracture within the past six months)
- Use of prescription medications affecting bone metabolism within three months
- Suicidality
- Psychosis
- Substance abuse
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 |
|---|---|---|
| Physiologic Estrogen/progesteroneAlso: Bone age >=15: Vivelle Dot patch with cyclic ProveraVivelle Dot patch 100 mcg twice weekly; Provera 2.5 mg daily for the first 10 days of the month | Drug | Physiologic estrogen replacement |
| PlaceboPlacebo patches twice weekly; Placebo pills daily for the first 10 days of every month | Other | Placebo |
Primary outcome
Percent Change in Spine Bone Density Over the Study Duration (18 Months)
Time frame: Baseline and 18 months
Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months. The primary outcome was the percent change in bone density at the spine from baseline to 18 months. Areal bone density is measured as g/cm2. The unit of measure for the percent change in bone density is 'percent' Percent change in bone density= [[Bone density at 18 months- Bone density at baseline)*100/Bone density at baseline]%
Change in Spine Bone Mineral Density Z-scores Over the Study Duration (18 Months)
Time frame: Baseline and 18 months
Bone density at the spine (lumbar 1-4 vertebrae) was measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 months, 12 months and 18 months. The other primary outcome was the change in spine bone density Z-score from baseline to 18 months. The bone density Z-score is a standard deviation score that compares one's bone density to the mean for age and gender, and the Z-score, therefore, does not have any units. It is simply referred to as a Z-score. Change in bone density Z-score= [Bone density Z-score at 18 months- Bone density Z-score at baseline]
1 secondary outcome
Change in N-terminal Propeptide of Type 1 Procollagen (P1NP) Over the Study Duration (18 Months)
Time frame: Baseline and 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21698665Misra M, Katzman D, Miller KK, Mendes N, Snelgrove D, Russell M, Goldstein MA, Ebrahimi S, Clauss L, Weigel T, Mickley D, Schoenfeld DA, Herzog DB, Klibanski A. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J Bone Miner Res. 2011 Oct;26(10):2430-8. doi: 10.1002/jbmr.447.
- Derived from this study: PubMed 24021517Misra M, Katzman DK, Estella NM, Eddy KT, Weigel T, Goldstein MA, Miller KK, Klibanski A. Impact of physiologic estrogen replacement on anxiety symptoms, body shape perception, and eating attitudes in adolescent girls with anorexia nervosa: data from a randomized controlled trial. J Clin Psychiatry. 2013 Aug;74(8):e765-71. doi: 10.4088/JCP.13m08365.
- Derived from this study: PubMed 22728230Faje AT, Fazeli PK, Katzman DK, Miller KK, Breggia A, Rosen CJ, Mendes N, Klibanski A, Misra M. Sclerostin levels and bone turnover markers in adolescents with anorexia nervosa and healthy adolescent girls. Bone. 2012 Sep;51(3):474-9. doi: 10.1016/j.bone.2012.06.006. Epub 2012 Jun 15.
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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 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 2/3 study testing Physiologic Estrogen/progesterone 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 2 inclusion and 8 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 2 Nov 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 10 Oct 2011). 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?
Percent Change in Spine Bone Density Over the Study Duration (18 Months) (time frame: Baseline and 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00088153, which also lists 3 linked publications.
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 2 Nov 2021.