Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00006174
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2000-08-11
Brief Title:
Effects of Letrozole on Precocious Puberty Due to McCune Albright Syndrome
Sponsor:
National Institute of Dental and Craniofacial Research NIDCR
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Effects of the Aromatase Inhibitor Letrozole on Pubertal Progression and Indices of Bone Turnover in Girls With Precocious Puberty and McCune-Albright Syndrome MAS
Status:
COMPLETED
Status Verified Date:
2009-05-18
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will test the safety and effectiveness of letrozole in treating precocious early puberty in girls with McCune-Albright syndrome MAS The physical changes of puberty such as breast enlargement menstruation and growth spurt as well as the emotional changes of this developmental stage usually begin in girls between the ages of 8 and 14 Girls with MAS however often begin puberty before age 7 In MAS large ovarian cysts produce high levels of estrogens female hormones that cause the changes of puberty Children with MAS also have polyostotic fibrous dysplasia PFD a disease of bones that depending on what parts of the skeleton are affected can lead to broken bones or disfigurement of the head face arms and legs or can cause pressure on nerves and blood vessels Many children with MAS have cafe-au-lait spots increased pigmentation on areas of their skin as well
Letrozole is an estrogen-lowering drug that has been approved for treating women with breast and other cancers Although the drug has not been tested or approved for use in children some pediatric specialists have given it to girls with precocious puberty and MAS and found that it improves their condition without harmful side effects This study will examine whether letrozole can lower estrogen in girls with MAS and arrest puberty It will also study the drugs effects on substances involved in bone growth including calcium phosphate and amino acids
Girls 1 to 8 years old with MAS may be eligible for this study Patients who were enrolled in NIH protocol 98-D-0145 Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and the McCune-Albright syndrome are also eligible Participants will be admitted to the hospital for 2 to 3 days every 3 months for 15 months for a total of 6 visits They will undergo a complete history and physical examination and routine blood and urine tests every visit as well as evaluations of their general health growth and bone development endocrine system hormone-secreting glands status and PFD status A hand X-ray will be taken at the first visit and every 6 months to measure bone age advance The children will begin taking letrozole at the second visit and continue the drug for 6 months They will be evaluated after 3 months and 6 months on the drug visits 3 and 4 and again after 3 months and 6 months after stopping treatment visits 5 and 6
Parents of children who weigh more than 18 kilograms about 40 pounds may be asked if extra blood may be drawn after 3 months visit 3 and 6 months visit 4 of treatment to measure letrozole levels The blood will be drawn before the morning dose and at 05 1 15 2 3 4 6 8 and 24 hours after the dose through an indwelling needle placed in the vein for 8 to 24 hours
Parents will keep a record of all episodes of menstrual bleeding and any other symptoms or complaints Children who respond well to therapy decreased menses slowed breast development slowed growth and bone age advance will be offered another 12 months of letrozole treatment
Letrozole is an estrogen-lowering drug that has been approved for treating women with breast and other cancers Although the drug has not been tested or approved for use in children some pediatric specialists have given it to girls with precocious puberty and MAS and found that it improves their condition without harmful side effects This study will examine whether letrozole can lower estrogen in girls with MAS and arrest puberty It will also study the drugs effects on substances involved in bone growth including calcium phosphate and amino acids
Girls 1 to 8 years old with MAS may be eligible for this study Patients who were enrolled in NIH protocol 98-D-0145 Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and the McCune-Albright syndrome are also eligible Participants will be admitted to the hospital for 2 to 3 days every 3 months for 15 months for a total of 6 visits They will undergo a complete history and physical examination and routine blood and urine tests every visit as well as evaluations of their general health growth and bone development endocrine system hormone-secreting glands status and PFD status A hand X-ray will be taken at the first visit and every 6 months to measure bone age advance The children will begin taking letrozole at the second visit and continue the drug for 6 months They will be evaluated after 3 months and 6 months on the drug visits 3 and 4 and again after 3 months and 6 months after stopping treatment visits 5 and 6
Parents of children who weigh more than 18 kilograms about 40 pounds may be asked if extra blood may be drawn after 3 months visit 3 and 6 months visit 4 of treatment to measure letrozole levels The blood will be drawn before the morning dose and at 05 1 15 2 3 4 6 8 and 24 hours after the dose through an indwelling needle placed in the vein for 8 to 24 hours
Parents will keep a record of all episodes of menstrual bleeding and any other symptoms or complaints Children who respond well to therapy decreased menses slowed breast development slowed growth and bone age advance will be offered another 12 months of letrozole treatment
Detailed Description:
Girls ages 1 - 8 years with the McCune-Albright syndrome MAS and girls with other conditions characterized by precocious puberty due to estrogen hypersecretion from ovarian cysts will be eligible for this pilot study Patients who have previously enrolled in Protocol 98-D-0145 Screening and natural history of patients with polyostotic fibrous dysplasia and the McCune-Albright Syndrome will also be eligible Patients will be treated with letrozole a potent nonsteroidal aromatase inhibitor to suppress their elevated serum estrogen levels We will confirm the safety and efficacy of letrozole and study its effectiveness in controlling the elevated sex steroid levels and the advanced rates of linear growth bone maturation and pubertal progression in these patients We will also study the effect of decreased estrogen levels on the status of their polyostotic fibrous dysplasia by measuring serum and urine values for bone biomarkers including calcium phosphate organic amino acids and vitamin D metabolites which are known to be abnormal in many patients with MAS Patients will act as their own controls We will compare serum and urine parameters of pubertal progression and bone biomarkers before during and after discontinuation of letrozole This trial will be carried out in parallel with in-vitro and in-vivo laboratory studies using an animal model of fibrous dysplasia In this model osteogenic precursor cells from patient bone biopsies will be cultured in a hydroxyapatitetricalcium phosphate matrix and transplanted into immunocompromised mice We anticipate that our laboratory findings will complement the care of our patients resulting in more effective treatment for the precocious puberty and the bone disease in children with MAS Because our initial studies have indicated that letrozole is effective in treating precocious puberty in MAS patients this protocol also enrolls girls who have a related condition gonadotropin-independent precocious puberty without the bone disease polyostotic fibrous dysplasia We also believe that this study complements the recent FDA and NIH mandates that children be included in the evaluation of pharmaceutical products and in federally funded clinical research studies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-D-0183 | None | None | None |