A Study of the Effects of Pegvisomant on Growth Hormone Excess in McCune-Albright Syndrome
A Study of the Effects of Pegvisomant on Growth Hormone Excess in McCune-Albright Syndrome
This study will examine the effect of pegvisomant on growth hormone excess in patients with
 McCune-Albright syndrome (MAS). Patients with this disease have polyostotic fibrous
 dysplasia-a condition in which areas of normal bone are replaced with fibrous growth similar
 to scar tissue, abnormal skin pigmentation (birth marks) and precocious (early) puberty.
 About 10 percent of patients have excess growth hormone (GH). GH stimulates the production of
 another hormone called insulin-like growth factor 1 (IGF-1). Together, GH and IGF-1 affect
 bone growth. The excess of these hormones in MAS can cause overgrowth of the bones of the
 face, hands and feet, excess sweating, or increased height.

 Pegvisomant is a synthetic drug that binds to cell receptors where GH would normally bind,
 thus preventing the naturally occurring hormone from stimulating IGF-1 and bone growth as it
 normally would. This study will see if pegvisomant will reduce blood levels of IGF-1 and
 mitigate the effects of growth hormone excess, including bone pain, bone turnover, hand and
 foot swelling and sweating, and abnormal levels of related hormones.

 Patients who were screened for polyostotic fibrous dysplasia and MAS under NIH protocol
 98-D-0145 and were found to have MAS with excess growth hormone are eligible for this 36-week
 study. The screening protocol includes a history and physical examination, blood and urine
 tests, hearing, eye and dental examinations, pain and physical function evaluations,
 endocrine and bone screening tests, various bone imaging studies, including magnetic
 resonance imaging (MRI) and computed tomography (CT) scans and bone biopsy in patients over 6
 years old.

 Participants in the current study will receive daily injections of either pegvisomant or
 placebo (an inactive substance) for 12 weeks, followed by a 6-week "washout" period with no
 drug. Then, patients who received placebo will be switched, or "crossed over," to receive
 pegvisomant for another 12 weeks, and those who received pegvisomant will receive placebo.
 This will be followed by another 6-week washout period. The drug and placebo will be injected
 under the skin, similar to insulin injections. Blood and urine tests will be done at the
 beginning of the study and repeated every 6 weeks until the study ends.
McCune-Albright Syndrome (MAS) was originally described as the triad of polyostotic fibrous
 dysplasia of bone, cafe-au-lait skin pigmentation and precocious puberty. Other endocrine
 abnormalities have been identified in this disease. Growth hormone (GH) excess is associated
 with MAS and occurs in approximately 10% of the patients. Current therapies of MAS involve
 separate treatment for the bone and endocrine diseases. We propose to test the effectiveness
 of a novel GH receptor antagonist, pegvisomant at reducing the growth hormone excess in these
 patients. Secondarily we shall also assess the impact of pegvisomant therapy on the fibrous
 dysplastic bone lesions associated with the disease.

 The subjects will be patients with MAS and non-suppressible growth hormone as determined by
 standard oral glucose tolerant testing (OGTT) and an elevated insulin-like growth factor-1
 (IGF-I). It will be a randomized, blinded crossover design. The primary and secondary
 measures of efficacy will be: the normalization of serum (IGF-I), a reduction in signs and
 symptoms of growth hormone excess, and a net change in Insulin-like Growth Factor Binding
 Protein 3 (IGFBP-3). The effect of pegvisomant on the fibrous dysplastic bone activity in
 these patients will be determined by a net change in the levels of bone turnover markers.
INCLUSION CRITERIA:

 Diagnosis of PFD/MAS as required in Protocol 98-D-0145

 Growth hormone excess will be determined as a non-suppressible serum growth hormone by oral
 glucose tolerance test (OGTT). The OGTT parameter will be serum GH greater than 2.0 ng/ml
 at 60 minutes after an oral load of 75g glucose.

 Two consecutive and duplicate measurements of serum IGF-I level should be at least 1.3
 times greater than the upper limit of normal (age and sex adjusted according to laboratory
 normal range).