Short Stature Clinical Trial
Official title:
Treatment With Recombinant Human Insulin-like Growth Factor 1 (rhIGF-1) in Patients With Pappalysin-2 (PAPP-A2) Gene Mutation.
Verified date | February 2024 |
Source | Children's Hospital Medical Center, Cincinnati |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
With this study we want to investigate the pharmacokinetic (PK) effect of a single injection of rhIGF-1 in patients with PAPP-A2 mutations compared to heterozygous carriers and healthy controls. This will be followed by treatment of PAPP-A2 deficient patients with IGF-1 for a period of one-year to assess growth velocity. Additionally, we want to further describe the phenotypic characteristics of patients with PAPP-A2 deficiency.
Status | Completed |
Enrollment | 7 |
Est. completion date | December 1, 2022 |
Est. primary completion date | October 14, 2022 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 10 Years and older |
Eligibility | PAPP-A2 deficient Inclusion Criteria: - Defect in PAPP-A2 (heterozygous or homozygous mutation) Exclusion Criteria: - None Healthy Volunteers Inclusion Criteria: - Between the ages of 18 and 30 - In general good health Exclusion Criteria: - Any medications (with the exception of contraceptives) - Pregnancy |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Children's Hospital Medical Center, Cincinnati |
Cabrera-Salcedo C, Mizuno T, Tyzinski L, Andrew M, Vinks AA, Frystyk J, Wasserman H, Gordon CM, Hwa V, Backeljauw P, Dauber A. Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and Effects on Glucose and Bone Density. J Clin Endocr — View Citation
Muthuvel G, Dauber A, Alexandrou E, Tyzinski L, Andrew M, Hwa V, Backeljauw P. Five-Year Therapy with Recombinant Human Insulin-Like Growth Factor-1 in a Patient with PAPP-A2 Deficiency. Horm Res Paediatr. 2023;96(5):449-457. doi: 10.1159/000529071. Epub — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Glucose Pre- and Post-treatment With Recombinant Human IGF-I | Observe nonparametric measures of glucose pre and post ongoing treatment with rhIGF-1. Oral glucose tolerance tests (OGTT) were performed annually during the five-year treatment period at pre-treatment (baseline) and post-initiation of treatment (after 12 months, 24 months, 36 months, 48 months, and 60 months). | Yearly until completion of the study, up to 6 years | |
Other | Insulin Metabolism Pre- and Post-treatment With Recombinant Human IGF-I | Observe nonparametric measures of insulin metabolism in each individual pre (baseline) and post ongoing treatment with rhIGF-1. Oral glucose tolerance testing (OGTT) was performed pre-treatment (baseline) and post-treatment (after 12 months, 24 months, 36 months, 48 months, and 60 months). | Annually through completion of the study, up to 6 years | |
Other | Body Mass Index at Baseline and on Treatment With rhIGF-I | Observe nonparametric measures of body composition pre (baseline) and post ongoing treatment with rhIGF-1 (assessed after 12 months, 24 months, 36 months, 48 months, and 60 months of rhIGF-1 treatment). BMI percentiles were determined utilizing Centers for Disease Control and Prevention growth charts. | Annually until completion of the study, up to 6 years | |
Other | Body Composition at Baseline and on Treatment With rhIGF-I | Observe nonparametric measures of body composition pre (baseline) and post ongoing treatment with rhIGF-1 (assessed after 12 months, 24 months, 36 months, 48 months, and 60 months of rhIGF-1 treatment). Body fat content and lean body mass were evaluated with dual energy x-ray absorptiometry. | Annually until completion of the study, up to 6 years | |
Other | Total Body Fat Percentage at Baseline and on Treatment With rhIGF-I | Observe nonparametric measures of body composition pre (baseline) and post ongoing treatment with rhIGF-1 (assessed after 12 months, 24 months, 36 months, 48 months, and 60 months of rhIGF-1 treatment). Body fat content and lean body mass were evaluated with dual energy x-ray absorptiometry. | Annually until completion of the study, up to 6 years | |
Other | C-telopeptide and Osteocalcin Concentrations at Baseline (Pre-treatment) and While on rhIGF-1. | Observe nonparametric measures of bone turnover pre-treatment (baseline) and post initiation of ongoing treatment (at 12 months, 24 months, 36 months, 48 months, and 60 months) while on rhIGF-1 | Yearly until completion of the study, up to 6 years | |
Other | Bone Density Pre-treatment (Baseline) and on Treatment With rhIGF-1 | Observe nonparametric measures of bone density at baseline (pre-treatment) and post initiation of ongoing treatment with rhIGF-1. Dual energy x-ray absorptiometry (DXA) was performed of total body less head, lumbar spine, hip, and forearm. Results are reported as height adjusted z-scores for age and gender, commonly done for bone density. A z-score of 0 is equivalent to population mean, positive above the mean, and negative below the mean. Z-scores within 2 standard deviations of the mean (Z-score 2 to -2) are generally considered normal, however are not sufficient to comment on presence or absence of osteoporosis in the pediatric population. | Annually until completion of therapy, up to 6 years | |
Other | Pharmacokinetic Description After Receiving Recombinant Human Insulin Like Growth Factor 1 (rhIGF-1): Maximum Corrected Total IGF-I and Free IGF-I | This was a pharmacokinetic assessment in regards to rhIGF-1 completed in siblings with PAPP-A2 deficiency, Participants received a 120 mcg/kg dose of rhIGF-1 (Increlex). Pharmacokinetic measurements were obtained over 24 hours. To isolate the effect of injected rhIGF-1, baseline-corrected concentrations were included by subtracting baseline concentration from measured concentrations. Results reported include maximum corrected total IGF-I and free IGF-I. Due to constraints of reporting platform, time to maximum values and area under the curve (AUC) 12 hours after the dose are reported as separate outcomes. | At baseline, prior to the ongoing treatment phase with rhIGF-1 | |
Other | Pharmacokinetic Description After Receiving Recombinant Human Insulin Like Growth Factor 1 (rhIGF-1): Time to Maximum Corrected Total IGF-I and Free IGF-I | This was a pharmacokinetic assessment in regards to rhIGF-1 completed in siblings with PAPP-A2 deficiency, Participants received a 120 mcg/kg dose of rhIGF-1 (Increlex). Pharmacokinetic measurements were obtained over 24 hours. To isolate the effect of injected rhIGF-1, baseline-corrected concentrations were included by subtracting baseline concentration from measured concentrations. Results reported include time to maximum corrected total IGF-I and free IGF-I. Due to constraints of reporting platform, maximum corrected total IGF-I and free IGF-I values and area under the curve (AUC) 12 hours after the dose are reported as separate outcomes. | At baseline, prior to the ongoing treatment phase with rhIGF-1 | |
Other | Pharmacokinetic Description After Receiving Recombinant Human Insulin Like Growth Factor 1 (rhIGF-1): Area Under the Curve | This was a pharmacokinetic assessment in regards to rhIGF-1 completed in siblings with PAPP-A2 deficiency, Participants received a 120 mcg/kg dose of rhIGF-1 (Increlex). Pharmacokinetic measurements were obtained over 24 hours. To isolate the effect of injected rhIGF-1, baseline-corrected concentrations were included by subtracting baseline concentration from measured concentrations. Results reported include area under the curve (AUC) 12 hours after the dose. Due to constraints of reporting platform, maximum corrected total IGF-I and free IGF-I, as well as time to maximum values separate outcomes. | At baseline, prior to the ongoing treatment phase with rhIGF-1 | |
Primary | Height Velocity | Height velocity in a patient with PAPP-A2 deficiency treated with rhIGF-1 for five years (when the patient elected to discontinue treatment after reviewing growth velocity and skeletal maturation). Ultimately only one patient was treated for the study duration with results reported, as the other recruited participant (sibling of the treated patient) experienced pseudotumor cerebri and discontinued treatment after 51 days. He nevertheless was followed, with height velocity also reported. | Yearly until participant on treatment stops growing, or discontinues treatment (up to 6 years) | |
Secondary | Height Standard Deviation Score | Height Standard Deviation Score is the standard deviation above or below the mean the height is for age and gender. Values were obtained by plotting heights on Centers for Disease Control and Prevention growth charts. An increase in Height Standard Deviation Score correlates with increase in height. Results are reported for the participant with PAPP-A2 deficiency treated with rhIGF-1, as well as sibling who did not continue treatment with rhIGF-1. | Annually until completion of study, up to 6 years | |
Secondary | Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship | Assess the PK/PD relationship (PD marker being IGFBP-3) annually while on treatment with rhIGF-1 | Yearly until completion of the study, up to 6 years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02826902 -
Effect of Anesthesia on Quality of Recovery in Patients Undergoing Correctional Tibial Osteotomy - A Randomized Controlled Trial
|
N/A | |
Completed |
NCT00235599 -
The IGFBP-3 Stimulation Test: A New Tool for the Diagnosis of Growth Hormone Deficiency in Children.
|
N/A | |
Completed |
NCT01911260 -
Weekly Zinc Chelate Supplementation on Children's Growth
|
Phase 2/Phase 3 | |
Completed |
NCT02137538 -
Aromatase Inhibitor Growth Study: Letrozole vs. Anastrozole
|
Phase 4 | |
Recruiting |
NCT01934270 -
Growth Hormone Secretion Following the Anaerobic Exercise
|
N/A | |
Completed |
NCT00443144 -
D3-GHR Polymorphism and Turner Syndrome
|
N/A | |
Recruiting |
NCT06295341 -
Short Stature and Psychological Well-being
|
||
Recruiting |
NCT05849389 -
Vosoritide for Short Stature in Turner Syndrome
|
Phase 2 | |
Recruiting |
NCT05829252 -
Testing the Feasibility of a Novel Growth Monitoring Smartphone App
|
||
Withdrawn |
NCT03323177 -
Long Term Effects of Nutritional Supplementation on Final Height
|
N/A | |
Completed |
NCT02389803 -
Evaluating the Effect of Nutritional Supplementation on Growth of Short and Lean Adolescents Boys
|
N/A | |
Recruiting |
NCT06294860 -
Biological Age in Children With GH Deficiency Undergoing Hormone Replacement Therapy
|
||
Recruiting |
NCT03123003 -
Bone Age Assessment in Children Using Ultrasound Compared to Wrist X-ray
|
N/A | |
Completed |
NCT03575221 -
Natural History of the Collagen-Related Disorder Osteogenesis Imperfecta and Genotype Phenotype Correlation
|
||
Terminated |
NCT01237041 -
Free Fatty Acids, Body Weight, and Growth Hormones Secretion in Children
|
Phase 1/Phase 2 | |
Completed |
NCT04244123 -
Web-based Adherence Information Integrated Nurse-led Monitoring Clinic
|
||
Recruiting |
NCT01901666 -
Assessment Of Gh-Igf-1 Axis In Children With Chronic Myelogenous Leukemia (CML) In Remission
|
Phase 4 | |
Withdrawn |
NCT01970800 -
The Role of Igf-1 Generation Test in Diagnosis and Treatment of Short Stature
|
N/A | |
Completed |
NCT00830141 -
Study of the Molecular Basis in the Pathophysiology of Food Intake and Growth in Children
|
N/A | |
Completed |
NCT00562705 -
Effects of Growth Hormone (GH) Treatment on Eating Regulation
|
N/A |