IGF-1 and Bone Loss in Women With Anorexia Nervosa

Mass General Brigham

Status: Completed

Conditions: Osteoporosis; Osteopenia; Anorexia Nervosa

Treatments: Drug: Placebo; Drug: Risedronate; Drug: rhIGF-1

Study type: Interventional

Funder types: Other

Identifiers

NCT01406444

2R01DK052625

Details and patient eligibility

About

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.

Enrollment: 148 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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148 participants in 3 patient groups, including a placebo group

rhIGF-1 followed by Risedronate

Active Comparator group

Description:

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

Treatment:

Drug: rhIGF-1

Drug: Risedronate

Risedronate

Active Comparator group

Description:

Risedronate 35mg PO once weekly for 12 months

Treatment:

Drug: Risedronate

Placebo

Placebo Comparator group

Description:

Placebo for 12 months

Treatment:

Drug: Placebo