Bronchopulmonary Dysplasia (BPD)Early Phase 1NCT07120971
Metformin for Premature Infants With Bronchopulmonary Dysplasia
A Early Phase 1 study testing Metformin (open-label) in people with Bronchopulmonary Dysplasia (BPD), run by Medical College of Wisconsin at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 days to 6 months
- Conditions the study is for
- Bronchopulmonary Dysplasia (BPD)
- What is being tested?
- Metformin (open-label)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2025to 1 Sep 2030
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 days to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- Persistent hypoglycemia
- Lactic acidosis
- Feeding intolerance
- Renal or hepatic dysfunction
- Active infection
- Congenital anomalies that preclude feedings
- Infants whose parents have chosen palliative care
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Wisconsin
Milwaukee, Wisconsin, 53226
Kathleen Meskin, BSN, RN, CCRP, 414-337-7171, kmeskin@mcw.edu
G. Ganesh Konduri, MD, MS
About this study
Official title: A Phase 0/Phase 1 Trial of Metformin for Premature Infants With Bronchopulmonary Dysplasia
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?
Read the 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.
- Conditions
- Bronchopulmonary Dysplasia (BPD)
- Being tested
- Metformin (open-label)
- Keywords
- bronchopulmonary dysplasia, BPD, prematurity, metformin
- Medical subject headings
- Bronchopulmonary Dysplasia, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin (open-label)Drug
Enteric metformin 5mg/kg/day in two divided doses will be given for three days to two subjects
Metformin (open-label)Drug
Enteric metformin 10mg/kg/day in two divided doses will be given for three days to two subjects.
Metformin (open-label)Drug
Enteric metformin 20mg/kg/day in two divided doses will be given for seven days to three subjects.
Metformin (open-label)Drug
Enteric metformin 25mg/kg/day in two divided doses will be given for 14 days to three subjects.
Metformin (open-label)Drug
Enteric metformin 15mg/kg/day in a single daily dose will be given for three days to 3-6 subjects. Depending on tolerance, the next Cohort will increase to 25mg/kg/day (Cohort 2) or decrease to 10mg/kg/day (Cohort 3)
Metformin (open-label)Drug
Enteric metformin 25mg/kg/day in a single daily dose will be given for three days to 3-6 subjects. Depending on tolerance, either 25mg/kg/day or 15mg/kg/day will be dose selected for the next Cohort (Cohort 4)
Metformin (open-label)Drug
Enteric metformin 10mg/kg/day in a single daily dose will be given for three days to 3-6 subjects. Depending on tolerance, either 10mg/kg/day dose selected for the next Cohort (Cohort 4) or the study will be stopped due to excessive toxicity.
Metformin (open-label)Drug
The dose for this cohort will be selected from either Cohort 2 or 3 based on tolerance. Enteric metformin 10-25mg/kg/day in a single daily dose will be given for seven days to 6 subjects.
Metformin (open-label)Drug
The dose for this cohort will be the same as Cohort 4. Enteric metformin 10-25mg/kg/day in a single daily dose will be given for 14 days to 6 subjects.
| Study group | Role | What they receive |
|---|---|---|
| Phase 0 - Cohort 1 | Experimental | 5mg/kg/day in two divided doses for three days Receives: Drug: Metformin (open-label) |
| Phase 0 - Cohort 2 | Experimental | 10mg/kg/day in two divided doses for three days Receives: Drug: Metformin (open-label) |
| Phase 0 - Cohort 3 | Experimental | 20mg/kg/day in two divided doses for seven days Receives: Drug: Metformin (open-label) |
| Phase 0 - Cohort 4 | Experimental | 25mg/kg/day in two divided doses for 14 days Receives: Drug: Metformin (open-label) |
| Phase 1 - Cohort 1 Escalation | Experimental | 15mg/kg/day in a single daily dose for three days Receives: Drug: Metformin (open-label) |
| Phase 1 - Cohort 2 Escalation | Experimental | 25mg/kg/day in a single daily dose for three days Receives: Drug: Metformin (open-label) |
| Phase 1- Cohort 3 Escalation | Experimental | 10mg/kg/day in a single daily dose for three days Receives: Drug: Metformin (open-label) |
| Phase 1 - Cohort 4 Expansion | Experimental | 10-25mg/kg/day (dose selected from either Cohort 2 or 3) Receives: Drug: Metformin (open-label) |
| Phase 1 - Cohort 5 Expansion | Experimental | 10-25mg/kg/day (dose selected from either Cohort 2 or 3) Receives: Drug: Metformin (open-label) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 14 days after administration of the first dose of metformin
Secondary outcomes (5)
Incidence of bronchopulmonary dysplasia
Number of subjects who are diagnosed with bronchopulmonary dysplasia
Measured: 14 days after administration of the first dose of metformin
Incidence of necrotizing enterocolitis
Number of subjects who are diagnosed with necrotizing enterocolitis
Measured: 14 days after administration of the first dose of metformin
Incidence of retinopathy of prematurity
Number of subjects who are diagnosed with retinopathy of prematurity
Measured: 14 days after administration of the first dose of metformin
Incidence of intraventricular hemorrhage
Number of subjects who are diagnosed with intraventricular hemorrhage
Measured: 14 days after administration of the first dose of metformin
Incidence of patent ductus arteriosus
Number of subjects who are diagnosed with patent ductus arteriosus
Measured: 14 days after administration of the first dose of metformin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2025
- Study start19 Dec 2025
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary Dysplasia (BPD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, G. Ganesh Konduri, Medical College of Wisconsin
- Investigators
- G. Ganesh Konduri, MD, MS, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07120971
- Sponsor's protocol ID
- PRO55881
- Status last verified
- Jan 2026
- First submitted
- 29 Jul 2025
- Last updated
- 26 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Since this is a small phase 0 and phase 1 study with enrollment of 4-30 infants from one site only in a short time frame, we are concerned about potential for unmasking the identification of individual identification from the sharing of individual patient data.
Publications
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.
PubMed 38869353Alemon-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.
PubMed 34602916Kirkpatrick 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.
PubMed 33029553Ayoub R, Ruddy RM, Cox E, Oyefiade A, Derkach D, Laughlin S, Ades-Aron B, Shirzadi Z, Fieremans E, MacIntosh BJ, de Medeiros CB, Skocic J, Bouffet E, Miller FD, Morshead CM, Mabbott DJ. Assessment of cognitive and neural recovery in survivors of pediatric brain tumors in a pilot clinical trial using metformin. Nat Med. 2020 Aug;26(8):1285-1294. doi: 10.1038/s41591-020-0985-2. Epub 2020 Jul 27.
PubMed 32719487Biag HMB, Potter LA, Wilkins V, Afzal S, Rosvall A, Salcedo-Arellano MJ, Rajaratnam A, Manzano-Nunez R, Schneider A, Tassone F, Rivera SM, Hagerman RJ. Metformin treatment in young children with fragile X syndrome. Mol Genet Genomic Med. 2019 Nov;7(11):e956. doi: 10.1002/mgg3.956. Epub 2019 Sep 14.
PubMed 31520524Brittain EL, Niswender K, Agrawal V, Chen X, Fan R, Pugh ME, Rice TW, Robbins IM, Song H, Thompson C, Ye F, Yu C, Zhu H, West J, Newman JH, Hemnes AR. Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension. J Am Heart Assoc. 2020 Nov 17;9(22):e018349. doi: 10.1161/JAHA.120.018349. Epub 2020 Nov 10.
PubMed 33167773Liao S, Li D, Hui Z, McLachlan CS, Zhang Y. Metformin added to bosentan therapy in patients with pulmonary arterial hypertension associated with congenital heart defects: a pilot study. ERJ Open Res. 2018 Aug 22;4(3):00060-2018. doi: 10.1183/23120541.00060-2018. eCollection 2018 Jul.
PubMed 30151369Wang X, Liu Y, Han D, Zhong J, Yang C, Chen X. Dose-dependent immunomodulatory effects of metformin on human neonatal monocyte-derived macrophages. Cell Immunol. 2022 Jul;377:104557. doi: 10.1016/j.cellimm.2022.104557. Epub 2022 Jun 3.
PubMed 35679651Jing Y, Wu F, Li D, Yang L, Li Q, Li R. Metformin improves obesity-associated inflammation by altering macrophages polarization. Mol Cell Endocrinol. 2018 Feb 5;461:256-264. doi: 10.1016/j.mce.2017.09.025. Epub 2017 Sep 18.
PubMed 28935544Howie SR. Blood sample volumes in child health research: review of safe limits. Bull World Health Organ. 2011 Jan 1;89(1):46-53. doi: 10.2471/BLT.10.080010. Epub 2010 Sep 10.
PubMed 21346890Autmizguine J, Benjamin DK Jr, Smith PB, Sampson M, Ovetchkine P, Cohen-Wolkowiez M, Watt KM. Pharmacokinetic studies in infants using minimal-risk study designs. Curr Clin Pharmacol. 2014;9(4):350-8. doi: 10.2174/1574884709666140520153308.
PubMed 24844642General clinical pharmacology considerations for neonatal studies for drugs and biological products- Guidance for industry. Food and Drug Administration. Clinical Pharmacology July 2022
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.
PubMed 38983827Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20. doi: 10.1093/jnci/djp079. Epub 2009 May 12.
PubMed 19436029DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism. 2016 Feb;65(2):20-9. doi: 10.1016/j.metabol.2015.10.014. Epub 2015 Oct 9.
PubMed 26773926