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Bone Loss in Women With Anorexia Nervosa

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Anne Klibanski, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00089843
First received: August 16, 2004
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

Women with Anorexia Nervosa have been found to have low bone density. The study will determine whether administration of low doses of a natural hormone, testosterone and/or risedronate, a medication to help prevent bone breakdown will improve or prevent bone loss in this condition.


Condition Intervention Phase
Anorexia Nervosa
Drug: Testosterone
Drug: Actonel (risedronate)
Drug: Placebo Actonel (risedronate)
Drug: Placebo testosterone
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: IGF-1 and Bone Loss in Women Anorexia Nervosa

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Bone Mineral Density [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Percent change in postero-anterior (PA) spine bone mineral density as measured by dual energy x-ray absorptiometry (DXA)over a 12-month period. The differences in log-transformed values are reported as percent change.


Secondary Outcome Measures:
  • Markers of Bone Metabolism [ Time Frame: Baseline to 12 months ] [ Designated as safety issue: No ]
    type 1 collagen C-telopeptide(CTX); The differences in log-transformed values are reported as percent change.


Enrollment: 77
Study Start Date: June 2003
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 2
Placebo Actonel (risedronate) and active testosterone patch
Drug: Testosterone
Testosterone patch 150mcg daily
Other Name: Intrinsa
Drug: Placebo Actonel (risedronate)
Placebo tablet identical in appearance to active Actonel (risedronate) tablet
Active Comparator: 3
Active Actonel (risedronate) and active testosterone patch
Drug: Testosterone
Testosterone patch 150mcg daily
Other Name: Intrinsa
Drug: Actonel (risedronate)
Actonel (risedronate) 35mg PO one time weekly
Other Name: Actonel
Active Comparator: 4
Active Actonel (risedronate) and placebo testosterone
Drug: Actonel (risedronate)
Actonel (risedronate) 35mg PO one time weekly
Other Name: Actonel
Drug: Placebo testosterone
Placebo patch identical in appearance to testosterone patch
Placebo Comparator: 1
Placebo testosterone patch and placebo Actonel (risedronate)
Drug: Placebo Actonel (risedronate)
Placebo tablet identical in appearance to active Actonel (risedronate) tablet
Drug: Placebo testosterone
Placebo patch identical in appearance to testosterone patch

Detailed Description:

II. SPECIFIC AIMS

Severe osteopenia is a prevalent complication of anorexia nervosa (AN), affecting over half of all women with this disease. Loss of 25-50% of total bone mass occurs frequently and is often permanent. Although anorexia nervosa affects from 0.5-1.0% of college age women, no successful therapeutic interventions have been developed for osteoporosis in this population. Bone loss in anorexia nervosa is characterized by reduced bone formation coupled with increased bone resorption. Anorexia nervosa results in a deficiency of testosterone. Testosterone administration reduces bone resorption and data suggest that low-dose testosterone replacement therapy can increase surrogate markers of bone formation. Bisphosphonates are now well established to decrease bone resorption and improve bone density in severely osteopenic postmenopausal women. However, there are few data regarding the use of this antiresorptive therapy in women with severe pre-menopausal bone loss. Our preliminary data demonstrate that administration of a bisphosphonate decreases bone resorption and increases bone mass in women with AN after 6 and 9 months. These are the first data to demonstrate a striking increase in bone density in such women. We will test the hypothesis that a combined strategy to increase bone formation and decrease bone resorption by combining testosterone with a bisphosphonate will increase bone mass in anorexia nervosa.

The following hypotheses will be tested:

Specific Aim 1. Testosterone, a nutritionally dependent bone trophic factor, is a critical determinant of decreased bone formation in anorexia nervosa, and administration of physiologic testosterone will increase bone formation and lean body mass in this disease

We will investigate in women with anorexia nervosa whether:

A. Bone formation is reduced in association with low serum testosterone B. Testosterone deficiency is due to a combination of ovarian and adrenal defects resulting from undernutrition C. Testosterone administration reverses testosterone deficiency leading to an acute and sustained increase in bone formation and a decrease in bone resorption D. Administration of physiologic testosterone replacement stimulates increases in IGF-I levels in women with anorexia nervosa, a mechanism for increased bone formation and bone density E. Administration of physiologic testosterone replacement increases lean body mass, a major determinant of bone density

Specific Aim 2. Long-term (12 months) physiologic testosterone administration combined with a bisphosphonate increases bone density by a dual anabolic and anti-resorptive strategy

We will investigate in women with anorexia nervosa whether:

A. Physiologic testosterone administration increases bone density B. Administration of a bisphosphonate decreases the excessive state of bone resorption and increases bone density C. Co-administration of physiologic testosterone replacement and a bisphosphonate increases bone density to a greater degree than testosterone or a bisphosphonate alone by increasing bone formation and decreasing bone resorption

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Anorexia Nervosa,
  • Over 18,
  • Female,
  • Decreased bone density

Exclusion Criteria:

  • Medications to increase bone density
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089843

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Anne Klibanski, M.D. Massachusetts General Hospital
  More Information

No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anne Klibanski, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00089843     History of Changes
Other Study ID Numbers: 5 R01 DK052625 (completed), R01DK052625, 1UL1RR025758
Study First Received: August 16, 2004
Results First Received: November 9, 2011
Last Updated: May 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Eating Disorders
Osteopenia

Additional relevant MeSH terms:
Anorexia
Anorexia Nervosa
Eating Disorders
Mental Disorders
Signs and Symptoms
Signs and Symptoms, Digestive
Etidronic Acid
Methyltestosterone
Risedronic acid
Testosterone
Testosterone 17 beta-cypionate
Testosterone enanthate
Testosterone undecanoate
Anabolic Agents
Androgens
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Bone Density Conservation Agents
Calcium Channel Blockers
Cardiovascular Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014