A Study of the Effects of Pegvisomant on Growth Hormone Excess in McCune-Albright Syndrome

NCT00017927 | Completed Phase 3

• 2 other identifiers: 01019701-D-0197
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

McCune Albright Syndrome; Polyostotic Fibrous Dysplasia

Keywords

Acromegaly; McCune-Albright Syndrome; IGF-1; Adenoma; Hyperplasia; MAS; Polyostotic Fibrous Dysplasia; PFD

Interventions

Pegvisomant DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

Sponsors & Collaborators

• National Institute of Dental and Craniofacial Research (NIDCR): lead

Study Sites (1)

National Institute of Dental And Craniofacial Research (NIDCR)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Chanson P, Dib A, Visot A, Derome PJ. McCune-Albright syndrome and acromegaly: clinical studies and responses to treatment in five cases. Eur J Endocrinol. 1994 Sep;131(3):229-34. doi: 10.1530/eje.0.1310229.

  PMID: 7921205 BACKGROUND

• Shenker A, Weinstein LS, Moran A, Pescovitz OH, Charest NJ, Boney CM, Van Wyk JJ, Merino MJ, Feuillan PP, Spiegel AM. Severe endocrine and nonendocrine manifestations of the McCune-Albright syndrome associated with activating mutations of stimulatory G protein GS. J Pediatr. 1993 Oct;123(4):509-18. doi: 10.1016/s0022-3476(05)80943-6.

  PMID: 8410501 BACKGROUND

• Mastorakos G, Mitsiades NS, Doufas AG, Koutras DA. Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report. Thyroid. 1997 Jun;7(3):433-9. doi: 10.1089/thy.1997.7.433.

  PMID: 9226216 BACKGROUND

MeSH Terms

Conditions

Fibrous Dysplasia, Polyostotic; Acromegaly; Adenoma; Hyperplasia

Interventions

pegvisomant

Condition Hierarchy (Ancestors)

Fibrous Dysplasia of Bone; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 20, 2001
• First Posted: June 21, 2001
• Study Start: June 1, 2001
• Study Completion: June 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-06

Locations

US (1)