X-linked dominant hypophosphatemic rickets (XLH)
Conditions
Interventions
experimental group:PEGylated Recombinant Human Growth Hormone (Jintrolong) combined with conventional therapy
control group:conventional therapy
Sponsors
Shandong Provincial Hospital Affiliated to Shandong First Medical University
Eligibility
Sex/Gender
All
Age
1 Years to 9 Years
Inclusion criteria
Inclusion criteria: (1) girls aged 1-8 years and boys aged 1-9 years who were prepubertal (Tanner stage 1: girls B1; G1 in boys, testicular volume < 3mL) in children was diagnosed XLH who met the following diagnostic criteria: ?there were clinical manifestations of hypophosphatemic rickets (such as skull deformity, dental lesions, beaded ribs, valgus ribs, pectus carinatum or pectus pectus, "bracelets or ankle-bracelets", genu varum or valgum, growth retardation, etc.), and calcium or vitamin D deficiency was excluded. ?Biochemical changes: hypophosphatemia (fasting serum phosphorus < 1.29 mmol/L or less than the lower limit of the reference range for the corresponding age), and renal phosphorus loss (increased urine phosphorus and decreased TmP/GFR) was considered, but other causes of hypophosphatemia were excluded (see exclusion criteria); Serum ALP increased; ?Bone lesions of rickets confirmed by imaging data; ?Patients with previous PHEX gene mutation test results, or family history of PHEX gene mutation (PHEX gene mutation test results can be provided) and in accordance with X-linked inheritance; (2) Meet the conditions for using growth hormone:?Well-controlled hypophosphatemic rickets: patients had been treated with phosphate mixture and calcitriol for at least 3 months (stable state: clinical, biochemical and radiological remission: rickets clinical remission; The levels of serum calcium, serum phosphorus at 2h after taking phosphorus, ALP and PTH were well controlled according to the clinician's evaluation, and the calcium-phosphorus product was = the lower limit of normal range. Imaging showed that active bone lesions were stationary). ?Skeletal deformity is not serious (severe cases see exclusion criteria) : after the doctor's evaluation, the use of growth hormone will not aggravate the original skeletal deformity; ?Indications for GH use: short stature for chronological age (< p10th percentile); ?There is still the potential for linear growth: the epiphysis has not closed, and the adult height has not been reached. ?There was no contraindication to the use of growth hormone, and no allergy to growth hormone and excipents. (3) At least 180 days before enrollment, no growth hormone of any type was required; (4) recorded objective height/length data for at least 3 months ±7 days before screening; (5) normal adrenocortical function and thyroid function; (6) They are willing to sign the informed consent form before the start of activities related to this trial, and they are able to understand the procedures and methods of this trial, and they are willing to strictly abide by the clinical trial protocol to complete all the treatment and visit plans of this trial, and cooperate with relevant examinations.
Exclusion criteria
Exclusion criteria: (1) rickets due to suspected vitamin D or calcium deficiency; (2) Suspected acquired hypophosphatemic rickets or other types of hereditary hypophosphatemic rickets: There are other causes of hypophosphatemia, such as insufficient phosphorus intake, reduced intestinal phosphorus absorption, redistribution of phosphorus in the body, excessive phosphorus loss from the digestive tract, or renal phosphorus loss from other causes, for example, primary hyperparathyroidism, tumor related hypophosphatemia, fibrous dysplasia of bone, McCune-Albright syndrome (MAS) or renal phosphorus loss caused by diseases of the kidney, such as Fanconi syndrome, hereditary hypophosphatemic rickets with hypercalciuria (such as hypercalciuria and/or SLC34A3 gene mutation), etc. (3) combined with other definite causes of growth failure and short stature, such as GHD, hypothyroidism, multiple pituitary hormone deficiencies, SGA, Turner syndrome, and other severe chronic disease-related short stature (such as malnutrition, cardiac insufficiency, hepatic and renal insufficiency, chronic inflammatory bowel disease); (4) Severe hypophosphatemic rickets: severe bone lesions (severe lower limb curve or scoliosis, with or without a history of osteotomy) or poor control of laboratory indicators (such as serum ALP > 800IU/L), who are not suitable for growth hormone treatment as assessed by doctors; (5) severe hypophosphatemic rickets related complications: severe nephrocalcinosis confirmed by ultrasound; Or uncontrolled severe secondary hyperparathyroidism (e.g. iPTH > 2 times the upper limit of normal); (6) hypercalcemia or hypocalcemia: serum calcium outside the reference range for age; (7) hypercalciuria, proteinuria, glucosuria, etc. (8) planned orthopedic surgery within one year, or fracture not healed; (9) Severe abnormal liver function: ALT or AST > 3 times of the upper limit of normal; Or patients with hepatitis B "big three positive" or other types of viral hepatitis; Patients with a history of alkylating agent application; (10) severe renal dysfunction: eGFR upper limit of normal; (11) patients with severe cardiovascular disease: including severe heart disease (such as cardiac function class ? and above, severe arrhythmia, etc.), poorly controlled hypertension (such as systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg under treatment) or higher than 95% of the corresponding age; (12) patients with severe brain disease: patients who were considered to be at risk for growth hormone replacement therapy if cranial MRI/CT showed intracranial mass or other abnormalities at screening/baseline; Or have a history of epilepsy. (13) patients with impaired glucose regulation (including impaired fasting glucose and impaired glucose tolerance) or diabetes; Family history of diabetes onset before 25 years old; (14) patients with other serious medical conditions affecting protocol completion, such as severe obesity, uncontrolled severe obstructive sleep apnea, active psychosis, severe infection, immunocompromised patients, etc. (15) Use of other drugs within the past 3 months that may affect the efficacy of the study endpoint: "These include other growth hormone drugs, aromatase inhibitors (including but not limited to letrozole and anastrozole), gonadotropin-releasing hormone analogues (including but not limited to triptorelin and leuprolide), sex hormones (including but not limit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| the changes of height standard deviation score by chronological age(?HtSDSCA); | — |
Secondary
| Measure | Time frame |
|---|---|
| the changes of height(?Ht);the changes of growth velocity(?GV);the changes of predicted adult height standard deviation score(?PAHSDS);the changes of predicted adult height(?PAH);the changes of Bone age/the changes of Bone age(?BA/?CA); | — |
Countries
China
Contacts
Public ContactLi Gui-Mei
Shandong Provincial Hospital Affiliated to Shandong First Medical University
Outcome results
None listed