IGF-1 and Bone Loss in Women With Anorexia Nervosa

Anorexia nervosa is an eating disorder that can cause thinning of the bones (a decrease in bone density). A significant decrease in bone density is called osteopenia or osteoporosis. Sometimes the loss of bone density can be severe enough to cause breaks and fractures of the bones. It is not known what causes the bones to thin in anorexia nervosa. Women who have this condition often have thin or weak bones that are more likely to break. They also have very low levels of a chemical called IGF-1 in their body. This chemical is very important for increasing bone growth in puberty and for maintaining healthy adult bones. The investigators would like to find out if giving rhIGF-1 followed by risedronate or risedronate alone can lead to an increase in bone formation, bone density, and bone strength in women with anorexia nervosa.

Study Overview

• Status: Completed
• Conditions: Anorexia Nervosa; Osteoporosis; Osteopenia
• Intervention / Treatment: Drug: rhIGF-1; Drug: Risedronate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age 18-45 years
• AN defined by DSM-IV diagnostic criteria, including weight less than 85% of ideal body weight (restricting or binge/purge type, BMI 15-17.5) OR meet criteria for sub-threshold AN, i.e., all DSM-IV criteria except that patients can have a BMI of <18.5 kg/m2 with or without amenorrhea
• Oral contraceptive use prior to enrollment
• BMD T score < -1.0
• Normal FSH and TSH or free T4
• Normal serum 25-OH vitamin D (>20 ng/mL) and calcium levels
• Ongoing care from a primary care provider
• Agree to use barrier contraception

Exclusion Criteria:

• Any subject with contraindications to risedronate
• Any subject with binge-purge subtype of anorexia nervosa who vomits regularly as their form of purging (vs. those who use laxatives or diuretics) and who have significant periodontal disease, tooth erosion or an invasive dental or periodontal procedure within the previous three months.
• Any disease known to affect bone, including untreated thyroid dysfunction, Cushing's or renal failure
• Any medication known to affect bone metabolism within 3 months of the study, excluding oral contraceptives. Bisphosphonates must have been discontinued for at least one year before participation
• Serum potassium <3.0 meq/L
• Serum ALT >3 times upper limit of normal
• eGFR of less than 30 ml/min
• Pregnant and/or breastfeeding
• Diabetes mellitus
• Active substance abuse, including alcohol
• History of malignancy
• Atraumatic fracture within the prior year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: rhIGF-1 followed by Risedronate; Sequential therapy with rhIGF-1 (started at a dose of 30 mcg/kg subcutaneous BID and titrated) for 6 months followed by 6 months of risedronate 35mg PO once weekly	Drug: rhIGF-1; Study participants will be started at a dose of 30 mcg/kg BID and will be titrated.; Other Names: Increlex; Drug: Risedronate; Risedronate 35mg PO one time weekly; Other Names: Actonel
ACTIVE_COMPARATOR: Risedronate; Risedronate 35mg PO once weekly for 12 months	Drug: Risedronate; Risedronate 35mg PO one time weekly; Other Names: Actonel
PLACEBO_COMPARATOR: Placebo; Placebo for 12 months	Drug: Placebo; Placebo injections 30 mcg/kg BID, Placebo tablet PO once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postero-anterior Spine Bone Mineral Density by DXA	Postero-anterior spine bone mineral density by dual-energy X-ray absorptiometry	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lateral Spine Bone Mineral Density by DXA	Lateral spine bone mineral density by dual-energy X-ray absorptiometry	12 Months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Study Director: Karen Miller, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): May 1, 2019
• Study Completion (ACTUAL): May 1, 2019

Study Registration Dates

• First Submitted: July 26, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (ESTIMATE): August 1, 2011

Study Record Updates

• Last Update Posted (ACTUAL): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 6, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Osteoporosis; Anorexia Nervosa; Bone density; Osteopenia
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Musculoskeletal Diseases; Bone Diseases; Anorexia; Anorexia Nervosa; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Risedronic Acid
• Other Study ID Numbers: 2R01DK052625 (NIH)