Effects of Anorexia Nervosa on Bone Mass in Adolescents

NCT00088153 | Completed Phase 2 Results DMC

• 2 other identifiers: DK062249R01DK062249
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anorexia Nervosa

Keywords

Anorexia Nervosa; Amenorrhea; Bone Mass; Growth hormone

Outcome Measures

Primary Outcomes (2)

• 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= \[\[Bone density at 18 months- Bone density at baseline)\*100/Bone density at baseline\]%

  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= \[Bone density Z-score at 18 months- Bone density Z-score at baseline\]

  Baseline and 18 months

Secondary Outcomes (1)

• Change in N-terminal Propeptide of Type 1 Procollagen (P1NP) Over the Study Duration (18 Months)

  Baseline and 18 months

Study Arms (2)

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

Drug: Physiologic Estrogen/progesterone

Placebo

PLACEBO COMPARATOR

Placebo patches or pills

Other: Placebo

Interventions

Physiologic Estrogen/progesterone DRUG

Vivelle Dot patch 100 mcg twice weekly; Provera 2.5 mg daily for the first 10 days of the month

Also known as: Bone age >=15: Vivelle Dot patch with cyclic Provera

Physiologic estrogen replacement

Placebo OTHER

Placebo patches twice weekly; Placebo pills daily for the first 10 days of every month

Placebo

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• The Hospital for Sick Children: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

• 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.

  PMID: 21698665 RESULT

• Misra 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.

  PMID: 24021517 DERIVED

• Faje 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.

  PMID: 22728230 DERIVED

MeSH Terms

Conditions

Anorexia Nervosa; Amenorrhea

Interventions

Progesterone

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Results Point of Contact

• Title: Anne Klibanski
• Organization: Massachusetts General Hospital

aklibanski@partners.org

617-726-3870

Study Officials

• Madhusmita Misra, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Pediatric Endocrinology

Study Record Dates

• First Submitted: July 20, 2004
• First Posted: July 21, 2004
• Study Start: July 1, 2003
• Primary Completion: February 1, 2011
• Study Completion: June 1, 2011
• Last Updated: November 2, 2021
• Results First Posted: October 10, 2011

Record last verified: 2021-10

Locations

US (1)