McCune Albright SyndromePhase 1NCT00006174
Effects of Letrozole on Precocious Puberty Due to McCune Albright Syndrome
A Phase 1 study testing Letrozole 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 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… Read more about this study
- Who is it for?
- Ages 1 year to 8 years, women only
- Conditions the study is for
- McCune Albright Syndrome, Polyostotic Fibrous Dysplasia, Precocious Puberty
- What is being tested?
- Letrozole
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2000to 18 May 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 1 year to 8 years
- Women only
- No healthy volunteers
- Child
Who may be able to join
- Patients will be girls age 1-8 years with precocious puberty (menses, and/or breast development, and/or BA greater than plus 2SD [for chronologic age] and/or linear growth rate greater than plus 2SD) and polyostotic fibrous dysplasia due to MAS.
- All ethnic groups will be included.
Who cannot join
- Boys with MAS will be excluded.
- Patients with clinically significant hepatic and/or renal impairment will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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)
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 drug's effects on substances involved in bone growth, including calcium, phosphate and amino acids.
Read more
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 0.5, 1, 1.5, 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.
Read the 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 hydroxyapatite/tricalcium 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.
- Being tested
- Letrozole
- Keywords
- Precocious Puberty, Polyostotic, Fibrous Dysplasia, PFD, McCune-Albright Syndrome (MAS)
- Medical subject headings
- Fibrous Dysplasia, Polyostotic, Puberty, Precocious, Fibrous Dysplasia of Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2000 (estimated)
- Study start3 Aug 2000
- Study completion18 May 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Enrolment
- 25 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
- NCT00006174
- Sponsor's protocol ID
- 000183
- Other IDs
- 00-D-0183
- Status last verified
- 18 May 2009
- First submitted
- 11 Aug 2000
- Last updated
- 2 Jul 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00006174
- Acronym / sponsor ID
- 000183
- Keywords
- Precocious Puberty, Polyostotic, Fibrous Dysplasia, PFD, McCune-Albright Syndrome (MAS)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)US National Institutes of Health
- Study start
- 3 Aug 2000
- Study completion
- 18 May 2009
- First posted
- 14 Aug 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 drug's 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 0.5, 1, 1.5, 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 hydroxyapatite/tricalcium 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 design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 1 year to 8 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Patients will be girls age 1-8 years with precocious puberty (menses, and/or breast development, and/or BA greater than plus 2SD [for chronologic age] and/or linear growth rate greater than plus 2SD) and polyostotic fibrous dysplasia due to MAS.
- All ethnic groups will be included.
Key exclusion criteria (2 listed)
- Boys with MAS will be excluded.
- Patients with clinically significant hepatic and/or renal impairment will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Letrozole | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
Related trials for McCune Albright Syndrome
RecruitingObservational study
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(Z)-Endoxifen in Girls With MAS-Associated Peripheral Precocious Puberty
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Fibrous Dysplasia, McCune-Albright Syndrome Patient Registry
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Letrozole 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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.