## Protocol Section
### Identification Module
**NCT ID:** NCT06429007

**Brief Title:** A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury

**Official Title:** A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury

#### Organization Study ID Info
**ID:** IRB-P00048370
#### Organization
**Class:** OTHER
**Full Name:** Boston Children's Hospital
### Status Module
#### Completion Date
**Date:** 2027-10-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-10-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-10-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Boston Children's Hospital

#### Responsible Party

**Investigator Affiliation:** Boston Children's Hospital

**Investigator Full Name:** Martha Sola-Visner

**Investigator Title:** Research Director, Department of Newborn Medicine

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care. Adjunctive treatments to promote brain repair are needed. The antidiabetic drug metformin has recently been recognized as a neurorestorative agent, but, to date, has not been used in infants. Herein, the investigator describes a clinical trial with the aim of demonstrating the safety and feasibility of metformin use to improve neurodevelopmental outcomes in infants with HIE.

### Conditions Module

**Conditions:**

- Hypoxic-Ischemic Encephalopathy

- HIE

- Neurodevelopment

- Infant Development

**Keywords:**

- HIE

- metformin

- Hypoxic-Ischemic Encephalopathy

- Pharmacokinetic modeling

- Neonates

- Brain Injury

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will complete a pre-study visit with baseline bloodwork including a complete blood count (CBC), liver and renal function, basic chemistry, glucose, and lactate. At this visit, parents will be taught how to administer metformin and given a 6-week supply of metformin at 50% of the target dose to minimize potential gastrointestinal upset. Parents will be educated on adverse effects and receive a diary to log dose administration and noted side effects. After six weeks, participants will return for a study visit with repeat labs. Bloodwork at this visit will include plasma metformin levels for measurement of pharmacokinetics. Study staff will also review diary completion for adverse effects and to ensure there have been no missed doses. Parents will then receive a 6-week supply of metformin 25mg/kg for 6 weeks. A final study visit will then occur following 12-weeks of metformin therapy, with repeat labs including plasma metformin levels.

**Intervention Names:**

- Drug: Metformin

**Label:** Metformin Intervention

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Metformin Intervention

**Description:** Infants in the study will receive 50% of the target dose (12.5mg/kg) for the first 6 weeks of participation. At the 6 week visit, the patient will be assessed and if found still eligible, will receive the full dose (25mg/kg) for the remaining 6 weeks of participation.

**Name:** Metformin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** A renal function panel (chem 10 with renal function) will be performed prior to the initiation of therapy and at all subsequent study visits.

**Measure:** Safety profile of kidney function

**Time Frame:** 12 weeks

**Description:** A liver function test (LFT) will be performed prior to the initiation of therapy and at all subsequent study visits.

**Measure:** Safety profile of liver function

**Time Frame:** 12 weeks

**Description:** To assess feasibility, the number of eligible patients will be compared to the number of patients who consent to participate in the study.

**Measure:** Recruitment feasibility

**Time Frame:** 12 weeks

#### Secondary Outcomes

**Description:** Plasma metformin levels will be analyzed by investigators with whole blood obtained at study visits.

**Measure:** Validity of neonatal model of metformin pharmacokinetics

**Time Frame:** 12 weeks

**Description:** Parents/caregivers will be sent a survey that utilizes a 5 point Likert scale to assess key factors that prevented or encouraged participation.

**Measure:** Stakeholder Satisfaction

**Time Frame:** 12 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Infants born \> 35 weeks' gestational age AND
* Received therapeutic hypothermia for clinically diagnosed HIE

Exclusion Criteria:

* Infants with known genetic or chromosomal disorders
* Infants with a liver or kidney disease that may affect drug metabolism
* Maternal metformin use while actively breastfeeding
* Infant weight is below the 10th percentile (as defined by World Health Organization) at time of study drug initiation.

**Maximum Age:** 6 Months

**Minimum Age:** 3 Months

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Vanessa.young@childrens.harvard.edu

**Name:** Vanessa Young, MS, RN

**Phone:** 617-355-8330

**Role:** CONTACT

**Contact 2:**

**Email:** katherine.eident@childrens.harvard.edu

**Name:** Kate Eident, BS

**Phone:** 617-355-2184

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Boston Children's Hospital

**Name:** Martha Sola-Visner, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000006259

- Term: Craniocerebral Trauma

- ID: D000020196

- Term: Trauma, Nervous System

- ID: D000014947

- Term: Wounds and Injuries

- ID: D000000860

- Term: Hypoxia

- ID: D000012818

- Term: Signs and Symptoms, Respiratory

- ID: D000002561

- Term: Cerebrovascular Disorders

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000002534

- Term: Hypoxia, Brain

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC26

- Name: Wounds and Injuries

- Abbrev: BC14

- Name: Heart and Blood Diseases

### Condition Browse Module - Browse Leaves

- ID: M10543

- Name: Ischemia

- Relevance: LOW

- As Found: Unknown

- ID: M4185

- Name: Hypoxia

- Relevance: LOW

- As Found: Unknown

- ID: M5207

- Name: Brain Injuries

- Relevance: HIGH

- As Found: Brain Injury

- ID: M5794

- Name: Brain Ischemia

- Relevance: HIGH

- As Found: Ischemic Encephalopathy

- ID: M5204

- Name: Brain Diseases

- Relevance: HIGH

- As Found: Encephalopathy

- ID: M22660

- Name: Hypoxia-Ischemia, Brain

- Relevance: HIGH

- As Found: Hypoxic Ischemic Encephalopathy

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M9349

- Name: Craniocerebral Trauma

- Relevance: LOW

- As Found: Unknown

- ID: M22023

- Name: Trauma, Nervous System

- Relevance: LOW

- As Found: Unknown

- ID: M15623

- Name: Signs and Symptoms, Respiratory

- Relevance: LOW

- As Found: Unknown

- ID: M5810

- Name: Cerebrovascular Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5783

- Name: Hypoxia, Brain

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001930

- Term: Brain Injuries

- ID: D000001927

- Term: Brain Diseases

- ID: D000002545

- Term: Brain Ischemia

- ID: D000020925

- Term: Hypoxia-Ischemia, Brain

### Intervention Browse Module - Ancestors

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Hemat

- Name: Hematinics

### Intervention Browse Module - Browse Leaves

- ID: M11667

- Name: Metformin

- Relevance: HIGH

- As Found: Assessment

- ID: M11110

- Name: Liver Extracts

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000008687

- Term: Metformin

### Misc Info Module

- Version Holder: 2024-05-31
