Bronchopulmonary Dysplasia (BPD)
Conditions
Keywords
bronchopulmonary dysplasia, BPD, prematurity, metformin
Brief summary
The overall objective of this study is to investigate the role of metformin in decreasing lung injury and promoting lung growth in premature infants. There are two phases to this pilot study. For Phase 0, the goal is to investigate the safety and tolerance of oral metformin in premature who have been diagnosed with bronchopulmonary dysplasia (BPD) at 36-44 weeks gestation. For Phase 1, the goal is to investigate metformin safety and tolerance in extremely premature infants who are 7-30 days old who have an increased risk of BPD. The main questions it aims to answer are: * how well do older premature infants tolerate metformin? * how well do younger premature infants tolerate metformin?
Detailed description
In Phase 0, there are four groups with different doses of metformin, starting at 5mg/kg/day to a maximum of 25mg/kg/day. Participants will take oral metformin twice a day for 3, 7 or 14 days, depending on which group they are in. In Phase 1, there are four groups with different doses of metformin, starting at 15mg/kg/day to a maximum of 25mg/kg/day. Participants will take oral metformin once a day for 3, 7, or 14 days, depending on what group they are in.
Interventions
Enteric metformin 5mg/kg/day in two divided doses will be given for three days to two subjects
Sponsors
Medical College of Wisconsin
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Days to 6 Months
Healthy volunteers
No
Inclusion criteria
Phase 0: * Birth gestational age of \< 29 weeks AND * Postnatal age between 8 and 22 weeks AND * Diagnosed with BPD at 36 weeks postnatal age Inclusion Criteria Phase 1: * Birth gestational age of \< 29 weeks, AND * Requiring mechanical ventilation or positive pressure support at 7 days postnatal age, AND * Postnatal age between 7 and 30 days
Exclusion criteria
* Persistent hypoglycemia * Lactic acidosis * Feeding intolerance * Renal or hepatic dysfunction * Active infection * Congenital anomalies that preclude feedings * Infants whose parents have chosen palliative care
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with treatment-related feeding problems | 14 days after administration of the first dose of metformin | Number of subjects who require a decrease in enteral feeding volume by \>50% from baseline |
| Number of subjects who require dose adjustments of metformin | 14 days after administration of the first dose of metformin | Number of subjects who need decreases in dose or discontinuation of metformin due to hepatic or renal dysfunction |
| Number of subjects who complete the treatment protocol | 14 days after administration of the first dose of metformin | Number of subjects who complete the study doses of enteric metformin |
| Number of subjects with respiratory deterioration | 14 days after administration of the first dose of metformin | Number of subjects who develop pneumonia and increases in oxygen concentration and ventilator support during the study |
| Number of subjects who complete pharmacokinetic evaluation of metformin | 14 days after administration of the first dose of metformin | Number of subjects who have at least one metformin concentration in blood measured at 1, 4 and 12 hours after an enteric dose |
| Pharmacokinetic analysis of metformin | 14 days after administration of the first dose of metformin | Area under the curve of Plasma Concentration Versus Time (AUC) of metformin over a time frame of 1, 4 and 12 hours after an enteric dose of metformin. |
| Number of participants who tolerate metformin | 14 days after administration of the first dose of metformin | Number of subjects who receive enteral doses of metformin and complete the study days without an adverse event while continuing enteral feedings |
| Number of participants with treatment-related adverse events | 14 days after administration of the first dose of metformin | Number of participants who develop hypoglycemia defined as blood glucose value \<50 |
| Number of participants with treatment-related metabolic acidosis | 14 days after administration of the first dose of metformin | Number of subjects who develop lactic acid levels \> 5mmol/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of patent ductus arteriosus | 14 days after administration of the first dose of metformin | Number of subjects who are diagnosed with patent ductus arteriosus |
| Incidence of necrotizing enterocolitis | 14 days after administration of the first dose of metformin | Number of subjects who are diagnosed with necrotizing enterocolitis |
| Incidence of retinopathy of prematurity | 14 days after administration of the first dose of metformin | Number of subjects who are diagnosed with retinopathy of prematurity |
| Incidence of intraventricular hemorrhage | 14 days after administration of the first dose of metformin | Number of subjects who are diagnosed with intraventricular hemorrhage |
| Incidence of bronchopulmonary dysplasia | 14 days after administration of the first dose of metformin | Number of subjects who are diagnosed with bronchopulmonary dysplasia |
Countries
United States
Contacts
CONTACTKathleen Meskin, BSN, RN, CCRP
PRINCIPAL_INVESTIGATORG. Ganesh Konduri, MD, MS
Medical College of Wisconsin
Outcome results
None listed