Polyostotic Fibrous DysplasiaPhase 2NCT00001728
Alendronate to Treat Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome
A Phase 2 study testing Fosamax (Alendronate) in people with Polyostotic Fibrous Dysplasia, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
Trial summary
This study will evaluate the effectiveness of alendronate in treating the bone abnormality in polyostotic fibrous dysplasia and McCune-Albright syndrome. In these diseases, areas of normal bone are replaced with a fibrous growth similar to a scar. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Polyostotic Fibrous Dysplasia
- What is being tested?
- Fosamax (Alendronate)
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 1998to 2 May 2011
- Phase
- Phase 2
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients must be concomitantly enrolled in the companion Screening and Natural History protocol.
- Any patient with at least 2 active fibrous dysplastic lesions of either the cranial, axial, or appendicular skeleton will be eligible for consideration for inclusion in the study. The diagnosis will be based on evidence typical findings on bone biopsy (performed during the "Screening" protocol). Final consideration for enrollment will depend on diagnosis at the NIH.
- Patients must be at least 6 years old.
- Patients may be of child-bearing age, but will be expected to be on a nonhormonal form of birth control that gives a 95% protection rate. If a patient becomes pregnant during the course of the study, they must withdraw but will be eligible for re-enrollment upon the completion of pregnancy and lactation.
- Patients on previous of concomitant therapy are eligible for enrollment. However, patients who have received previous treatment with a bisphosphonate must wait one year from the completion of the last course before they can be enrolled.
Who cannot join
- Patient, child or parents unwilling to fully cooperate with the evaluation as outlined in the schedule and consent form and do not give informed consent.
- Any sexually active patient that is unwilling to use an appropriate contraceptive associated with a pregnancy-prevention rate of 95% or greater.
- Pregnancy is an absolute contraindication to be evaluated or admitted to the study and is grounds for removal from the study. However, patients may be re-enrolled once pregnancy and lactation are completed.
- Severe esophageal motility problems may put patients at increased risk for complications from alendronate and are not eligible for the study.
- Significant comorbidities such as decompensated heart failure or diabetes mellitus, renal or hepatic failure, or decompensated psychiatric conditions exclude patients from enrollment.
- Patients with either a history of sarcoma of the bone or who have a FD lesion that undergoes sarcomatous degeneration while enrolled in either this study or any of the companion protocols.
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: A Randomized, Placebo-Controlled Trial of Alendronate in the Treatment of Polyostotic Fibrous Dysplasia and the McCune-Albright Syndrome
This study will evaluate the effectiveness of alendronate in treating the bone abnormality in polyostotic fibrous dysplasia and McCune-Albright syndrome. In these diseases, areas of normal bone are replaced with a fibrous growth similar to a scar. The weakened bone causes pain and increases patients' risk of bone fractures and bone deformities. Alendronate belongs to a class of drugs called "bisphosphonates," which are approved by the Food and Drug Administration to treat bone weakening, deformity and pain in other medical conditions. It is thought that bisphosphonates might work by slowing the activity of osteoclasts-cells that break down bone.
Patients 12 years of age and older with polyostotic fibrous dysplasia or McCune-Albright syndrome may be eligible for this 3-year study. Candidates must also be enrolled in NIDCR's protocol 98-D-0145 (Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome).
Read more
Participants will be randomly assigned to one of two treatment groups: they will take one capsule a day of either alendronate or placebo (a look-alike capsule that has no active ingredient). They will take the capsules for 6 months, stop for 6 months, then take them for another 6 months and then go off them for 6 months. They will then remain off the drug or placebo for an additional 12 months and complete the study with a final follow-up visit at 36 months. While taking alendronate or placebo, patients will also take calcium and vitamin D to prevent secondary hyperparathyroidism-a side effect of alendronate in which the bone does not release enough calcium.
Patients will come to NIH for a physical examination and blood and urine tests every 6 months and for monitoring of their bone disease, vision, hearing, pain levels, functional evaluation, and photographs every 12 months. Many of the monitoring procedures, including imaging studies and biopsies, are performed for the screening protocol (98-D-0145) and will not be duplicated for this study. During the study periods when patients are taking alendronate or placebo, they will have blood samples drawn by their local physician once every 3 months and sent to NIH to check for secondary hyperparathyroidism.
If at the end of the study alendronate is found to be effective, patients who were in the placebo treatment group will be offered alendronate for a 24-month period.
Read the detailed description
Polyostotic fibrous dysplasia (PFD) is a sporadic disorder which affects multiple sites in the skeleton. The bone at these sites is rapidly resorbed and replaced by abnormal fibrous tissue and mechanically abnormal bone. PFD may occur alone or as part of the McCune-Albright Syndrome (MAS), a syndrome originally defined by the triad of PFD, cafe-au-lait pigmentation of the skin, and precocious puberty. The bony lesions are frequently disfiguring and painful, and depending on the location of the lesion, they can cause significant morbidity. Lesions in weight-bearing bones can lead to disabling fractures, while lesions in the skull can lead to compression of vital structures such as cranial nerves.
Currently there are no clearly-defined systemic therapies for this bone disease. Small, uncontrolled trials using the second generation bisphosphonate, pamidronate, suggest that bisphosphonates may be effective. This study is a phase 2, controlled, double blinded trial of the third generation oral bisphosphonate, alendronate for the treatment of fibrous dysplasia. We propose to show that treatment with alendronate will improve bone quality, decrease bone pain, decrease fractures, and, if the patient is referred to the companion bone grafting protocol, will allow for the regeneration of better quality bone.
- Conditions
- Polyostotic Fibrous Dysplasia
- Being tested
- Fosamax (Alendronate)
- Keywords
- Bone Marrow Stromal Cells, Bone Turnover, Fibrous Dysplastic Lesion, Polyostotic Fibrous Dysplasia, McCune-Albright Syndrome
- Medical subject headings
- Fibrous Dysplasia, Polyostotic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fosamax (Alendronate)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start24 Aug 1998
- Primary completion19 Aug 2007
- Study completion2 May 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Polyostotic Fibrous DysplasiaStudies 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 2
- Primary purpose
- Treatment
- Enrolment
- 40 participants (actual)
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
- NCT00001728
- Sponsor's protocol ID
- 980146
- Other IDs
- 98-D-0146
- Status last verified
- 2 May 2011
- First submitted
- 3 Nov 1999
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Liens D, Delmas PD, Meunier PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet. 1994 Apr 16;343(8903):953-4. doi: 10.1016/s0140-6736(94)90069-8.
PubMed 7909013Czerwiec FS, Collins M, Feuillan P, Shenker A. Further study of the therapy for fibrous dysplasia is necessary. J Bone Miner Res. 1997 Dec;12(12):2128-30. doi: 10.1359/jbmr.1997.12.12.2128. No abstract available.
PubMed 9421248Mastorakos 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 9226216Boyce AM, Kelly MH, Brillante BA, Kushner H, Wientroub S, Riminucci M, Bianco P, Robey PG, Collins MT. A randomized, double blind, placebo-controlled trial of alendronate treatment for fibrous dysplasia of bone. J Clin Endocrinol Metab. 2014 Nov;99(11):4133-40. doi: 10.1210/jc.2014-1371. Epub 2014 Jul 17.
PubMed 25033066
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
- A Randomized, Placebo-Controlled Trial of Alendronate in the Treatment of Polyostotic Fibrous Dysplasia and the McCune-Albright Syndrome
- ClinicalTrials.gov ID
- NCT00001728
- Acronym / sponsor ID
- 980146
- Conditions
- Polyostotic Fibrous Dysplasia
- Keywords
- Bone Marrow Stromal Cells, Bone Turnover, Fibrous Dysplastic Lesion, Polyostotic Fibrous Dysplasia, McCune-Albright Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)US National Institutes of Health
- Study start
- 24 Aug 1998
- Primary completion
- 19 Aug 2007 (actual)
- Study completion
- 2 May 2011 (actual)
- First posted
- 4 Nov 1999 (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 evaluate the effectiveness of alendronate in treating the bone abnormality in polyostotic fibrous dysplasia and McCune-Albright syndrome. In these diseases, areas of normal bone are replaced with a fibrous growth similar to a scar. The weakened bone causes pain and increases patients' risk of bone fractures and bone deformities. Alendronate belongs to a class of drugs called "bisphosphonates," which are approved by the Food and Drug Administration to treat bone weakening, deformity and pain in other medical conditions. It is thought that bisphosphonates might work by slowing the activity of osteoclasts-cells that break down bone.
Patients 12 years of age and older with polyostotic fibrous dysplasia or McCune-Albright syndrome may be eligible for this 3-year study. Candidates must also be enrolled in NIDCR's protocol 98-D-0145 (Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome).
Participants will be randomly assigned to one of two treatment groups: they will take one capsule a day of either alendronate or placebo (a look-alike capsule that has no active ingredient). They will take the capsules for 6 months, stop for 6 months, then take them for another 6 months and then go off them for 6 months. They will then remain off the drug or placebo for an additional 12 months and complete the study with a final follow-up visit at 36 months. While taking alendronate or placebo, patients will also take calcium and vitamin D to prevent secondary hyperparathyroidism-a side effect of alendronate in which the bone does not release enough calcium.
Patients will come to NIH for a physical examination and blood and urine tests every 6 months and for monitoring of their bone disease, vision, hearing, pain levels, functional evaluation, and photographs every 12 months. Many of the monitoring procedures, including imaging studies and biopsies, are performed for the screening protocol (98-D-0145) and will not be duplicated for this study. During the study periods when patients are taking alendronate or placebo, they will have blood samples drawn by their local physician once every 3 months and sent to NIH to check for secondary hyperparathyroidism.
If at the end of the study alendronate is found to be effective, patients who were in the placebo treatment group will be offered alendronate for a 24-month period.
Detailed description
Polyostotic fibrous dysplasia (PFD) is a sporadic disorder which affects multiple sites in the skeleton. The bone at these sites is rapidly resorbed and replaced by abnormal fibrous tissue and mechanically abnormal bone. PFD may occur alone or as part of the McCune-Albright Syndrome (MAS), a syndrome originally defined by the triad of PFD, cafe-au-lait pigmentation of the skin, and precocious puberty. The bony lesions are frequently disfiguring and painful, and depending on the location of the lesion, they can cause significant morbidity. Lesions in weight-bearing bones can lead to disabling fractures, while lesions in the skull can lead to compression of vital structures such as cranial nerves.
Currently there are no clearly-defined systemic therapies for this bone disease. Small, uncontrolled trials using the second generation bisphosphonate, pamidronate, suggest that bisphosphonates may be effective. This study is a phase 2, controlled, double blinded trial of the third generation oral bisphosphonate, alendronate for the treatment of fibrous dysplasia. We propose to show that treatment with alendronate will improve bone quality, decrease bone pain, decrease fractures, and, if the patient is referred to the companion bone grafting protocol, will allow for the regeneration of better quality bone.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- All patients must be concomitantly enrolled in the companion Screening and Natural History protocol.
- Any patient with at least 2 active fibrous dysplastic lesions of either the cranial, axial, or appendicular skeleton will be eligible for consideration for inclusion in the study. The diagnosis will be based on evidence typical findings on bone biopsy (performed during the "Screening" protocol). Final consideration for enrollment will depend on diagnosis at the NIH.
- Patients must be at least 6 years old.
- Patients may be of child-bearing age, but will be expected to be on a nonhormonal form of birth control that gives a 95% protection rate. If a patient becomes pregnant during the course of the study, they must withdraw but will be eligible for re-enrollment upon the completion of pregnancy and lactation.
- Patients on previous of concomitant therapy are eligible for enrollment. However, patients who have received previous treatment with a bisphosphonate must wait one year from the completion of the last course before they can be enrolled.
Key exclusion criteria (6 listed)
- Patient, child or parents unwilling to fully cooperate with the evaluation as outlined in the schedule and consent form and do not give informed consent.
- Any sexually active patient that is unwilling to use an appropriate contraceptive associated with a pregnancy-prevention rate of 95% or greater.
- Pregnancy is an absolute contraindication to be evaluated or admitted to the study and is grounds for removal from the study. However, patients may be re-enrolled once pregnancy and lactation are completed.
- Severe esophageal motility problems may put patients at increased risk for complications from alendronate and are not eligible for the study.
- Significant comorbidities such as decompensated heart failure or diabetes mellitus, renal or hepatic failure, or decompensated psychiatric conditions exclude patients from enrollment.
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 |
|---|---|---|
| Fosamax (Alendronate) | 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.
- Background: PubMed 7909013Liens D, Delmas PD, Meunier PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet. 1994 Apr 16;343(8903):953-4. doi: 10.1016/s0140-6736(94)90069-8.
- Background: PubMed 9421248Czerwiec FS, Collins M, Feuillan P, Shenker A. Further study of the therapy for fibrous dysplasia is necessary. J Bone Miner Res. 1997 Dec;12(12):2128-30. doi: 10.1359/jbmr.1997.12.12.2128. No abstract available.
- Background: PubMed 9226216Mastorakos 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.
- Derived from this study: PubMed 25033066Boyce AM, Kelly MH, Brillante BA, Kushner H, Wientroub S, Riminucci M, Bianco P, Robey PG, Collins MT. A randomized, double blind, placebo-controlled trial of alendronate treatment for fibrous dysplasia of bone. J Clin Endocrinol Metab. 2014 Nov;99(11):4133-40. doi: 10.1210/jc.2014-1371. Epub 2014 Jul 17.
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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 2 study testing Fosamax (Alendronate) in people with 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 5 inclusion and 6 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
On the ClinicalTrials.gov record for NCT00001728, which also lists 4 linked publications.
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.