McCune Albright SyndromePhase 3NCT00017927
A Study of the Effects of Pegvisomant on Growth Hormone Excess in McCune-Albright Syndrome
A Phase 3 study testing Pegvisomant in people with McCune Albright Syndrome and Polyostotic Fibrous Dysplasia, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- McCune Albright Syndrome, Polyostotic Fibrous Dysplasia
- What is being tested?
- Pegvisomant
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2001to Jun 2005
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Dental And Craniofacial Research (NIDCR)
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the detailed description
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.
- Being tested
- Pegvisomant
- Keywords
- Acromegaly, McCune-Albright Syndrome, IGF-1, Adenoma, Hyperplasia, MAS, Polyostotic Fibrous Dysplasia, PFD
- Medical subject headings
- Fibrous Dysplasia, Polyostotic, Acromegaly, Adenoma, Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegvisomantDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2001 (estimated)
- Study startJun 2001
- Study completionJun 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for McCune Albright SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Enrolment
- 10 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00017927
- Sponsor's protocol ID
- 010197
- Other IDs
- 01-D-0197
- Status last verified
- Jun 2005
- First submitted
- 20 Jun 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
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.
PubMed 7921205Shenker 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.
PubMed 8410501Mastorakos 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.
PubMed 9226216