NCT00310791

Brief Summary

This study seeks to gain new information on why young women with anorexia nervosa are predisposed to early bone loss and osteoporosis. Through a randomized treatment trial in which participants will receive either combined therapy with the adrenal hormone, dehydroepiandrosterone (DHEA) and estrogen replacement therapy or placebo, we will determine the effects of an 18-month treatment course on bone mass, circulating markers of bone turnover, and serum levels of a factor, insulin-like growth factor I (IGF-I). We are also studying if these therapies change bone structure to increase skeletal strength compared to placebo, as assessed through cross-sectional geometric analysis of our bone density data by dual-energy x-ray absorptiometry (DXA).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Apr 2004

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2004

Completed
2 years until next milestone

First Submitted

Initial submission to the registry

April 3, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 5, 2006

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2009

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2010

Completed
2.2 years until next milestone

Results Posted

Study results publicly available

February 1, 2013

Completed
Last Updated

April 11, 2018

Status Verified

March 1, 2018

Enrollment Period

5.5 years

First QC Date

April 3, 2006

Results QC Date

June 22, 2011

Last Update Submit

March 15, 2018

Conditions

Anorexia Nervosa

Keywords

anorexia nervosaadolescentsdual-energy x-ray absorptiometrydehydroepiandrosterone (DHEA)osteoporosis

Outcome Measures

Primary Outcomes (1)

  • Areal Bone Density by DXA

    18-Months

Study Arms (2)

Sugar Pill

PLACEBO COMPARATOR

Placebo (sugar pill); identical to treatment medication capsule

Other: Placebo (Sugar Pill)

DHEA + Hormone replacement therapy (estrogen/progestin)

EXPERIMENTAL

Combined therapy of dehydroepiandrosterone (DHEA) and hormone replacement therapy (ERT). Patients randomized to the DHEA + HRT arm will receive micronized oral DHEA in a dose of 50 mg daily + HRT (0.3 mg Premarin, 1 tablet daily for 3 months, follow by Alesse (20 mg ethinyl estradiol + 0.1 mg levonorgestrel for 15 months). The estrogen/progestin component of the regimen has been chosen to maximize patient compliance, as patients with AN may experience bloating or nausea if higher estrogen doses (\> 20 g) are initiated too rapidly. The DHEA capsule strength will be 50 mg, the total daily dose to be studied in combination with HRT. The micronized DHEA preparation achieves more constant DHEA and DHEA-S levels. Fifty milligrams appears to be a physiological replacement dose for these young women, determined both from our pilot (10) and longitudinal studies (7).

Drug: Hormone replacement therapy (estrogen/progestin)Drug: Dehydroepiandrosterone (DHEA)

Interventions

Hormone replacement therapy (estrogen/progestin)DRUG

Hormone replacement therapy (estrogen/progestin). 0.3 mg conjugated estrogens x 3 months, followed by 9 months of oral contraceptive (20 mg ethinyl estradiol + 0.1 mg levonorgestrel)

Also known as: Alesse (20 mg ethinyl estradiol + 0.1 mg levonorgestrel), Premarin (conjugated estrogens)
DHEA + Hormone replacement therapy (estrogen/progestin)
Placebo (Sugar Pill)OTHER

Placebo (sugar pill)

Also known as: Placebo, Sugar pill
Sugar Pill
Dehydroepiandrosterone (DHEA)DRUG

50 mg tablet, 1 daily

Also known as: Prasterone
DHEA + Hormone replacement therapy (estrogen/progestin)

Eligibility Criteria

Age15 Years - 30 Years
Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Age 15 - 30 years
  • Anorexia nervosa by psychiatric criteria
  • Amenorrhea for at least 3 months

You may not qualify if:

  • Receiving no medications known to affects bone metabolism
  • No other chronic medical conditions

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Related Publications (10)

  • Vajapeyam S, Ecklund K, Mulkern RV, Feldman HA, O'Donnell JM, DiVasta AD, Rosen CJ, Gordon CM. Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa. Bone. 2018 May;110:335-342. doi: 10.1016/j.bone.2018.02.021. Epub 2018 Feb 26.

    PMID: 29496516BACKGROUND

  • Divasta AD, Feldman HA, Brown JN, Giancaterino C, Holick MF, Gordon CM. Bioavailability of vitamin D in malnourished adolescents with anorexia nervosa. J Clin Endocrinol Metab. 2011 Aug;96(8):2575-80. doi: 10.1210/jc.2011-0243. Epub 2011 Jun 1.

    PMID: 21632810RESULT

  • Divasta AD, Feldman HA, Gordon CM. Vertebral fracture assessment in adolescents and young women with anorexia nervosa: a case series. J Clin Densitom. 2014 Jan-Mar;17(1):207-11. doi: 10.1016/j.jocd.2013.02.011. Epub 2013 Apr 3.

    PMID: 23562364RESULT

  • DiVasta AD, Feldman HA, Beck TJ, LeBoff MS, Gordon CM. Does hormone replacement normalize bone geometry in adolescents with anorexia nervosa? J Bone Miner Res. 2014 Jan;29(1):151-7. doi: 10.1002/jbmr.2005.

    PMID: 23744513RESULT

  • DiVasta AD, Mulkern RV, Gordon CM, Ecklund K. MR Imaging in a case of severe anorexia nervosa: the 'flip-flop' effect. Pediatr Radiol. 2015 Apr;45(4):617-20. doi: 10.1007/s00247-014-3145-3. Epub 2014 Aug 17.

    PMID: 25129340RESULT

  • Donaldson AA, Feldman HA, O'Donnell JM, Gopalakrishnan G, Gordon CM. Spinal Bone Texture Assessed by Trabecular Bone Score in Adolescent Girls With Anorexia Nervosa. J Clin Endocrinol Metab. 2015 Sep;100(9):3436-42. doi: 10.1210/jc.2015-2002. Epub 2015 Jun 24.

    PMID: 26108094RESULT

  • DiVasta AD, Feldman HA, O'Donnell JM, Long J, Leonard MB, Gordon CM. Effect of Exercise and Antidepressants on Skeletal Outcomes in Adolescent Girls With Anorexia Nervosa. J Adolesc Health. 2017 Feb;60(2):229-232. doi: 10.1016/j.jadohealth.2016.10.003. Epub 2016 Dec 6.

    PMID: 27939877RESULT

  • DiVasta AD, Feldman HA, O'Donnell JM, Long J, Leonard MB, Gordon CM. Skeletal outcomes by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in adolescent girls with anorexia nervosa. Osteoporos Int. 2016 Dec;27(12):3549-3558. doi: 10.1007/s00198-016-3685-5. Epub 2016 Jul 8.

    PMID: 27392467RESULT

  • Bialo SR, Gordon CM. Underweight, overweight, and pediatric bone fragility: impact and management. Curr Osteoporos Rep. 2014 Sep;12(3):319-28. doi: 10.1007/s11914-014-0226-z.

    PMID: 24986712RESULT

  • Ecklund K, Vajapeyam S, Mulkern RV, Feldman HA, O'Donnell JM, DiVasta AD, Gordon CM. Bone marrow fat content in 70 adolescent girls with anorexia nervosa: Magnetic resonance imaging and magnetic resonance spectroscopy assessment. Pediatr Radiol. 2017 Jul;47(8):952-962. doi: 10.1007/s00247-017-3856-3. Epub 2017 Apr 22.

    PMID: 28432403RESULT

MeSH Terms

Conditions

Anorexia NervosaOsteoporosis

Interventions

Hormone Replacement TherapyEstrogensProgestinsEthinyl Estradiol-Norgestrel CombinationEthinyl EstradiolLevonorgestrelEstrogens, Conjugated (USP)SugarsDehydroepiandrosterone

Condition Hierarchy (Ancestors)

Feeding and Eating DisordersMental DisordersBone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Drug TherapyTherapeuticsHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesNorpregnatrienesNorpregnanesNorsteroidsSteroidsFused-Ring CompoundsPolycyclic CompoundsNorgestrelNorpregnenesEstrogenic Steroids, AlkylatedEstradiol CongenersGonadal Steroid HormonesGonadal HormonesCarbohydratesAndrostenolsAndrostenesAndrostanes17-KetosteroidsKetosteroidsAdrenal Cortex HormonesTestosterone Congeners

Results Point of Contact

Title
Dr. Catherine Gordon
Organization
Children's Hospital Boston
cgordon1@lifespan.org
401-444-4712

Study Officials

  • Catherine M. Gordon, MD

    Boston Children's Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Catherine Gordon, MD, MSc

Study Record Dates

First Submitted

April 3, 2006

First Posted

April 5, 2006

Study Start

April 1, 2004

Primary Completion

October 1, 2009

Study Completion

December 1, 2010

Last Updated

April 11, 2018

Results First Posted

February 1, 2013

Record last verified: 2018-03

Locations

US(1)