IGF-1 and Bone Loss in Women With Anorexia Nervosa

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
IGF-1 and Bone Loss in Women With Anorexia Nervosa

Conditions
-----------------
Anorexia Nervosa, Osteopenia, Osteoporosis

Intervention / Treatment
-----------------
* Drug: rhIGF-1
* Drug: Risedronate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rhIGF-1 followed by Risedronate<br>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<br>* Study participants will be started at a dose of 30 mcg/kg BID and will be titrated.<br>* Other names: Increlex;Drug: Risedronate<br>* Risedronate 35mg PO one time weekly<br>* Other names: Actonel;|
| Active Comparator: Risedronate<br>Risedronate 35mg PO once weekly for 12 months | Drug: Risedronate<br>* Risedronate 35mg PO one time weekly<br>* Other names: Actonel;|
| Placebo Comparator: Placebo<br>Placebo for 12 months | Drug: Placebo<br>* Placebo injections 30 mcg/kg BID, Placebo tablet PO once weekly<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anorexia Nervosa, Osteopenia, Osteoporosis, Bone density