5 Clinical Trials for Various Conditions
Background: Fibrous dysplasia (FD) is a disorder that affects bone growth. Affected bone tissue is weakened, and people with FD are prone to deformities, fractures, and other problems. People with FD may also have low blood phosphate levels. This can make bones even weaker. Better treatments are needed. Objective: To test a study drug (burosumab) in people with FD who have low blood phosphate levels. Eligibility: People aged 1 year or older who have FD and low blood phosphate levels. Design: Participants will visit the NIH 3 times in 48 weeks. Each visit will last 5 to 7 days. Participants will self-inject burosumab under the skin in their belly, upper arm, or thigh. They (or a caregiver) will do this at home 1 or 2 times a month. They will be trained in person on how to inject the drug. Home injections will be guided via telehealth. During NIH visits, participants will have a physical exam with blood and urine tests. They will have x-rays of different parts of their body. They will have a radioactive tracer injected into their vein; then they will have a bone scan. They will have tests to assess their strength, walking, and movement. They will complete questionnaires about their pain, mobility, and fatigue levels. Adult participants may have bone biopsies. These will be done under anesthesia with sedation. Small samples of FD-affected bone will be removed for study. Between NIH visits, participants will go to a local laboratory for blood and urine tests. Child participants will have an additional follow-up visit 2 weeks after the final NIH visit.
This study will evaluate the effectiveness of a new bone injection technique for treating bone disease in patients with polyostotic fibrous dysplasia or McCune-Albright syndrome. In these patients, some bones develop areas with much less mineral, making the bones more prone to fracture or deformity and causing pain. This new treatment is intended to reduce the risk of fracture, minimize deformities and improve overall function in these patients. Patients 4 years of age and older with bone lesions that are highly likely to cause significant pain and illness may be eligible for this 2-year study. Participants must be simultaneously enrolled in NIDCR's research protocol 98-D-0145 (Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome) or 98-D-0146 (A Randomized, Placebo-Controlled Trial of Alendronate in the Treatment of Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome). Within 14 days of the bone injection procedure, patients will have a medical history, routine blood tests, urinalysis and check of vital signs (blood pressure, pulse and temperature) and will complete a 30-minute quality-of-life questionnaire. Women of child-bearing potential will have a pregnancy test. Patients who do not have recent X-rays and bone density scans available for review will have new ones taken. When these studies are completed, patients will undergo the bone injection procedure, followed immediately by bone densitometry and coned-down X-rays, as follows: * Bone injection - Patients will be given an anesthetic either to make them sleepy or put them to sleep completely. A portion of bone marrow will be withdrawn through a needle inserted into the hip bone and, at the same time, abnormal bone in the arms and legs will be sucked out using a needle. The abnormal bone will be replaced with a mixture of bone marrow and collagen (connective tissue protein) injected into the hole in the bone. The areas of injection will be closed * Bone densitometry - X-rays of the operated bone and opposite normal bone will be taken. * Coned-down X-rays - Magnified normal X-rays will be taken as close-ups of an active lesion. Patients will have a history and physical examination by their local physician or at NIH every month for the first 4 months after the procedure. Every 6 months after the procedure, patients will return to NIH for follow-up, including a physical examination and completion of a quality-of-life questionnaire. Imaging studies of the injected site will be done 3, 6, and 12 months after the procedure.
This study will investigate how a gene mutation (change in DNA) causes the abnormal bone in fibrous dysplasia-a condition in which areas of normal bone are replaced with a fibrous growth similar to a scar. The bone abnormalities in fibrous dysplasia can occur in a single bone (monostotic fibrous dysplasia), multiple bones (polyostotic fibrous dysplasia), or in McCune Albright syndrome, in which there are associated glandular abnormalities. This study will also examine calcinosis samples that have been surgically removed from patients with juvenile dermatomyositis. Patients who are scheduled to have orthopedic surgery for treatment of polyostotic fibrous dysplasia may participate in this study. A small sample of bone tissue removed during surgery will be given to investigators in this study for research tests. DNA will be extracted from the tissue and tested for the mutation. Investigators will attempt to grow cells from the sample in the laboratory to evaluate them for their ability to grow and make proteins that normal bone cells make. These tests are designed to help scientists understand how the mutation leads to abnormal bone formation and provide information that might lead to better treatments for fibrous dysplasia. Patients with juvenile Dermatomyositis who have a calcinosis sample surgically removed are also eligible for participation. The removed tissues will be examined for their composition and microscopic appearance, to better understand the pathogenesis of dystrophic calcification in this disease.
Objectives: The primary objective of this study is to evaluate the effect of denosumab on bone turnover in individuals with fibrous dysplasia (FD). Secondary objectives are to determine the effect of denosumab on bone pain, FD lesion intensity as revealed in 18F-sodium fluoride PET/CT bone scan, and to determine the effect of denosumab discontinuation on bone turnover re-bound after discontinuation. Study Population: Up to 14 adult subjects with FD may be enrolled to ensure complete study data on 9 subjects. Design: This study is a single center, open label pilot study of once-monthly dosing of denosumab. Subjects will be treated for 6 months, after which they will be followed by an 8-month observation period. A final visit will occur 21 months after denosumab discontinuation. Dosing will be adopted from studies in adults on treatment for giant cell tumors, with denosumab administered at 120 mg per dose every 4 weeks, with loading doses on days 7 and 14 of month 1. Outcome Measures: Primary: Assessment of the effects of denosumab on: 1. Markers of bone turnover: Beta-crosslaps C-telopeptides (bone resorption marker) Procollagen-1-propeptide (bone formation marker) Secondary: Assessment of the effects of denosumab on: 1. Bone histomorphometric indices: Mineralized perimeter Bone formation rate Cortical width Cortical area Osteoid width Osteoid perimeter Mineral apposition rate 2. Surrogate markers of a direct therapeutic effect of denosumab on FD lesions: Semi-quantitative changes in RANKL, Ki67 (marker of cell proliferation), p16 (marker of cell senescence), and/or apoptosis index before and after treatment, as assessed by immunohistochemistry Changes in sentinel lesion intensity, measured quantitatively by uptake on 18Fsodium fluoride PET/CT bone scan. 3. FD-related bone pain assessed by the Brief Pain Inventory (Short Form) , a validated self-reporting tool for assessment of pain. Exploratory Endpoints: 1. Effect of denosumab initiation and discontinuation on Serum calcium, phosphorus and parathyroid hormone Serum RANKL and osteoprotegerin (OPG), and RANKL/OPG levels 2. Effect of denosumab discontinuation, as measured by the following outcomes: Biochemical markers of bone metabolism: beta-crosslaps C-telopeptides, procollagen-1 propeptide, bone specific alkaline phosphatase, osteocalcin, NTX-telopeptides 3. Effect measured by change in other outcome measures, such as: Bone density assessed by DXA Physical Medicine and Rehabilitation evaluation
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.