View clinical trials related to Hypophosphatemia.
Filter by:The primary objective of this study is to establish the effect of KRN23 treatment on improvement in XLH-associated osteomalacia as determined by osteoid volume (osteoid volume/bone volume, OV/BV).
The primary efficacy objective of this study is to establish the effect of burosumab treatment compared with placebo on increasing serum phosphorus levels in adults with XLH.
The primary objectives of this study are to: - Assess the long-term safety of KRN23 subcutaneous (SC) administration in adult subjects with XLH - Assess the proportion of subjects achieving serum phosphorus levels in the normal range (2.5-4.5 mg/dL) with long-term administration of KRN23 - Assess long-term pharmacodynamics (PD) of KRN23 as measured by changes in the following: serum intact parathyroid hormone (iPTH); serum and urinary phosphorus; ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) and tubular reabsorption of phosphate (TRP); serum 1,25-dihydroxy vitamin D (1,25[OH]2D); serum fibroblast growth factor 23 (FGF23); bone biomarkers: serum alkaline phosphatase (ALP), bone-specific ALP (BALP), carboxy terminal crosslinked telopeptide of type I collagen (CTx), and procollagen type 1 N-terminal propeptide (P1NP) - Assess long-term immunogenicity of KRN23 as measured by presence of anti-KRN23 antibody (ADA)
The objectives of the study are to: - Identify a dose and dosing regimen of burosumab, based on safety and pharmacodynamic (PD) effect, in pediatric XLH participants - Establish the safety profile of burosumab for the treatment of children with XLH including ectopic mineralization risk, cardiovascular effects, and immunogenicity profile - Characterize the pharmacokinetic (PK)/PD profile of the KRN23 doses tested in the monthly (Q4) and biweekly (Q2) dose regimens in pediatric XLH patients - Determine the PD effects of burosumab treatment on markers of bone health in pediatric XLH patients - Obtain a preliminary assessment of the clinical effects of burosumab on bone health and deformity, muscle strength, and motor function - Obtain a preliminary assessment of the effects of burosumab on participant-reported outcomes, including pain, disability, and quality of life in pediatric XLH patients - Evaluate the long-term safety and efficacy of burosumab
Background: - Hypophosphatemia is a condition where a person has low levels of phosphorus in the blood. Low blood phosphorus can cause muscle and bone weakness (such as rickets) and teeth problems. One cause of the condition is having too much fibroblast growth factor 23 (FGF23). FGF23 is a hormone that causes the kidney to get rid of phosphorus in the urine. It can also prevent the body from making vitamin D, which helps the body absorb phosphorus in food. - Many people with low blood phosphorus take high doses of phosphorus and calcium medications. However, one side effect of these drugs is increased blood levels of parathyroid hormone (PTH). The drug cinacalcet can help lower PTH levels, which may decrease the amount of phosphorus lost in the urine and increase the phosphorus levels in the blood. Researchers want to see if cinacalcet can help blood phosphorus and decrease the amount of phosphorus supplements that people need to take. Objectives: - To see if cinacalcet can be a safe and effective treatment for people with low phosphorus conditions due to high FGF23. Eligibility: - Individuals between 18 and 70 years of age who have different forms of hypophosphatemic rickets and tumor-induced hypophosphatemia Design: - Participants will have up to 25 study visits over about 28 weeks. - Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. - Up to three more lab visits for blood and urine tests will be required before treatment. Imaging studies of the bones, spine, and kidneys will be performed. - Participants will have a 3-night hospital stay to start treatment. They will take cinacalcet once a day. Treatment will be monitored with frequent blood tests and imaging studies. - Participants will continue to take cinacalcet once a day for 3 weeks. They will have regular study visits to monitor the treatment. - There will be up to two other overnight hospital stays (1 to 3 nights) to adjust cinacalcet doses. The dose will increase until the maximum dose is reached, or side effects develop. - After the end of the cinacalcet study, participants will have several more followup visits to monitor the effects of treatment.
There is a deficit in the number of 'age-appropriate' formulations available for the delivery of medicines to children. Liquid preparations are considered the 'gold standard' for delivering medicines to children however many of these are formulated using ingredients which can be toxic to children (e.g. preservatives, alcohols), particularly to neonatal babies (< 4 weeks old) who do not possess the metabolic processes and mature organ function of older children or adults. Rapidly dissolving oral thin films (OTFs) dissolve quickly in the saliva, releasing the active ingredient(s) without the need for chewing or water, making them ideally suited to patients who find it difficult to swallow other oral dosage forms such as tablets or capsules. The aim of this study is to demonstrate that OTFs can offer a safe and effective alternative for oral administration of phosphate supplements to neonatal infants for the treatment of hypophosphataemia and osteopenia of prematurity. It is hypothesised that this treatment will be equal to standard therapy using an oral solution. Babies born before 32 weeks gestational age are routinely supplemented with oral phosphate as soon as they have been established on oral feeds in order to prevent bone disorders such as osteopenia. Babies recruited to this study will be given phosphate supplementation as per NHS Greater Glasgow and Clyde guidelines. This single-centre cross-over study will take place in the intensive care and special care baby units at the Princess Royal Maternity in Glasgow. The investigators aim to recruit 20-30 babies and will use blood phosphate levels (obtained from routine sampling only) to evaluate treatment effect. Babies will be randomised to receive either OTFs or oral solution of potassium acid phosphate for 2 weeks followed by 2 weeks of the other therapy. The investigators hypothesise that OTF treatment will be equivalent to standard oral solution.
Fibroblast froth factors (FGFs) are humoral factors identified by their ability to stimulate cell proliferation1. They play different roles in the regulation of cell proliferation, differentiation and function. Most FGF family members act as paracrine factors. But FGF19(FGF19) subfamily members, including FGF19, 21, and 23, work as endocrine factors to regulate bile acid, carbohydrate and phosphate metabolism2. Of these, FGF23 plays an important role in phosphate and bone metabolism3. FGF23 gene encodes 251 amino acids, including a 24-amino acid signal peptide4. The secreted FGF23 is a protein consisted of 227 amino acids. It works by binding to a Klotho-FGF receptor 1c (FGF1c) complex5. FGF suppresses the expression of type 2a and 2c sodium-phosphate cotransporters, which mediate phosphate reabsorption in proximal tubules.6 FGF23 decreases 25-hydroxyvitamin D-1α-hydroxylase expression and enhances 25-hydroxyvitamin D-24-hydroxylase expression6. Therefore, FGF23 reduces serum 1,25-dihydroxyvitamin D〔1,25(OH)2D〕, which stimulates intestinal calcium and phosphate absorption. FGF23 decreases serum phosphate through the above mechanisms FGF23 over-expression might result in hypophosphatemic rickets and osteomalacia. Tumor induced osteomalacia (TIO) is a paraneoplastic syndrome usually caused by benign phosphaturic mesenchymal tumors. Symptoms are nonspecific, such as general weakness, fatigue, and bone pain. Sometimes fracture may occurs. The responsible tumors are sometimes small and difficult to detect. Tumors secrete FGF23. FGF23 reduced phosphate reabsorption in the proximal tubules and decrease 1,25(OH)2D levels, which result in hypophosphatemia and then osteomalacia. The investigators would like to observe the changes of FGF23 in patients who receive operation or medical treatment and hope this will benefit future treatment.
X-linked hypophosphatemia (XLH) is the most common form of inherited rickets in the United States. It also causes bone disease in adults. XLH is caused by overproduction of a hormone call FGF23, which makes the body waste phosphate. This study is designed to determine if nasal calcitonin, an already approved drug in the US, can lower blood levels of FGF23 and reduce phosphate wasting in patients with XLH. In this study the investigators will: 1. Determine whether nasal calcitonin significantly lowers integrated 24-hour blood levels of FGF23 in patients with XLH. 2. Evaluate whether nasal calcitonin improves serum phosphate levels in XLH. 3. Assess whether nasal calcitonin improves blood levels of the active form of vitamin D and calcium absorption from the intestine. 4. Make sure that nasal calcitonin is safe and well tolerated.
The primary purpose of this study is to assess the safety and efficacy of repeated subcutaneous (SC) injections of KRN23 in adult subjects with X-Linked Hypophosphatemia (XLH).
The primary purpose of this study is to assess the safety and efficacy of repeated subcutaneous (SC) injections of KRN23 in adult subjects with X-Linked Hypophosphatemia (XLH). A Bone Substudy will evaluate the effects of single-blind KRN23 versus Placebo on bone mineral density and bone quality.