Metformin for Premature Infants With Bronchopulmonary Dysplasia

NCT07120971 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: PRO55881
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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?

Conditions

Bronchopulmonary Dysplasia (BPD)

Keywords

bronchopulmonary dysplasia; BPD; prematurity; metformin

Outcome Measures

Primary Outcomes (9)

• Number of participants who tolerate metformin

  Number of subjects who receive enteral doses of metformin and complete the study days without an adverse event while continuing enteral feedings

  14 days after administration of the first dose of metformin

• Number of participants with treatment-related adverse events

  Number of participants who develop hypoglycemia defined as blood glucose value \<50

  14 days after administration of the first dose of metformin

• Number of participants with treatment-related metabolic acidosis

  Number of subjects who develop lactic acid levels \> 5mmol/L

  14 days after administration of the first dose of metformin

• Number of subjects with treatment-related feeding problems

  Number of subjects who require a decrease in enteral feeding volume by \>50% from baseline

  14 days after administration of the first dose of metformin

• Number of subjects who require dose adjustments of metformin

  Number of subjects who need decreases in dose or discontinuation of metformin due to hepatic or renal dysfunction

  14 days after administration of the first dose of metformin

• Number of subjects with respiratory deterioration

  Number of subjects who develop pneumonia and increases in oxygen concentration and ventilator support during the study

  14 days after administration of the first dose of metformin

• Number of subjects who complete pharmacokinetic evaluation 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

  14 days after administration of the first dose of metformin

• Pharmacokinetic analysis 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.

  14 days after administration of the first dose of metformin

• Number of subjects who complete the treatment protocol

  Number of subjects who complete the study doses of enteric metformin

  14 days after administration of the first dose of metformin

Secondary Outcomes (5)

• Incidence of bronchopulmonary dysplasia

  14 days after administration of the first dose of metformin

• Incidence of necrotizing enterocolitis

  14 days after administration of the first dose of metformin

• Incidence of retinopathy of prematurity

  14 days after administration of the first dose of metformin

• Incidence of intraventricular hemorrhage

  14 days after administration of the first dose of metformin

• Incidence of patent ductus arteriosus

  14 days after administration of the first dose of metformin

Study Arms (9)

Phase 0 - Cohort 1

EXPERIMENTAL

5mg/kg/day in two divided doses for three days

Drug: Metformin (open-label)

Phase 0 - Cohort 2

EXPERIMENTAL

10mg/kg/day in two divided doses for three days

Drug: Metformin (open-label)

Phase 0 - Cohort 3

EXPERIMENTAL

20mg/kg/day in two divided doses for seven days

Drug: Metformin (open-label)

Phase 0 - Cohort 4

EXPERIMENTAL

25mg/kg/day in two divided doses for 14 days

Drug: Metformin (open-label)

Phase 1 - Cohort 1 Escalation

EXPERIMENTAL

15mg/kg/day in a single daily dose for three days

Drug: Metformin (open-label)

Phase 1 - Cohort 2 Escalation

EXPERIMENTAL

25mg/kg/day in a single daily dose for three days

Drug: Metformin (open-label)

Phase 1- Cohort 3 Escalation

EXPERIMENTAL

10mg/kg/day in a single daily dose for three days

Drug: Metformin (open-label)

Phase 1 - Cohort 4 Expansion

EXPERIMENTAL

10-25mg/kg/day (dose selected from either Cohort 2 or 3)

Drug: Metformin (open-label)

Phase 1 - Cohort 5 Expansion

EXPERIMENTAL

10-25mg/kg/day (dose selected from either Cohort 2 or 3)

Drug: Metformin (open-label)

Interventions

Metformin (open-label) DRUG

Enteric metformin 5mg/kg/day in two divided doses will be given for three days to two subjects

Phase 0 - Cohort 1

Eligibility Criteria

• Age: 7 Days - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Birth gestational age of \< 29 weeks AND
• Postnatal age between 8 and 22 weeks AND
• Diagnosed with BPD at 36 weeks postnatal age
• 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

You may not qualify if:

• Persistent hypoglycemia
• Lactic acidosis
• Feeding intolerance
• Renal or hepatic dysfunction
• Active infection
• Congenital anomalies that preclude feedings
• Infants whose parents have chosen palliative care

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Publications (23)

• Rana U, Joshi C, Whitney E, Afolayan A, Dowell J, Teng RJ, Konduri GG. Decreased Liver Kinase B1 Expression and Impaired Angiogenesis in a Murine Model of Bronchopulmonary Dysplasia. Am J Respir Cell Mol Biol. 2024 Oct;71(4):481-494. doi: 10.1165/rcmb.2024-0037OC.

  PMID: 38869353 BACKGROUND

• Alemon-Medina R, Altamirano-Bustamante N, Lugo-Goytia G, Garcia-Alvarez R, Rivera-Espinosa L, Torres-Espindola LM, Chavez-Pacheco JL, Juarez-Olguin H, Gomez-Garduno J, Flores-Perez C, Fernandez-Perez PG. Comparative Bioavailability and Pharmacokinetics Between the Solid Form of Metformin vs a Novel Liquid Extemporaneous Formulation in Children. Dose Response. 2021 Sep 27;19(3):15593258211033140. doi: 10.1177/15593258211033140. eCollection 2021 Jul-Sep.

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• Kirkpatrick EC, Mitchell ME, Thilly WG, Cava J, Tomita-Mitchell A, Gostjeva EV. Use of Metformin in Pulmonary Vein Stenosis after TAPVR Repair. Glob Pediatr Health. 2020 Sep 25;7:2333794X20958924. doi: 10.1177/2333794X20958924. eCollection 2020. No abstract available.

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• General clinical pharmacology considerations for neonatal studies for drugs and biological products- Guidance for industry. Food and Drug Administration. Clinical Pharmacology July 2022

  BACKGROUND

• See KC. Metformin-associated lactic acidosis: A mini review of pathophysiology, diagnosis and management in critically ill patients. World J Diabetes. 2024 Jun 15;15(6):1178-1186. doi: 10.4239/wjd.v15.i6.1178.

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• Hutchinson AM, Pais R, Endginton AN, Pilon B, MacDonald JM, MacDonald ME, Lewis T, Offringa M, Kalish BT. Safety and feasibility trial protocol of metformin in infants after perinatal brain injury. BMJ Paediatr Open. 2025 Aug 24;9(1):e002784. doi: 10.1136/bmjpo-2024-002784.

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MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• G. Ganesh Konduri, MD, MS

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathleen Meskin, BSN, RN, CCRP

CONTACT

414-337-7171; kmeskin@mcw.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Division Chief of Neonatology

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: August 13, 2025
• Study Start: December 19, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2030
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)