Metformin for Cerebral Palsy

No longer recruiting at 1 trial location

Overseen By Eisha Amjad

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Holland Bloorview Kids Rehabilitation Hospital

Must not be taking: Diuretics, Cationic drugs, others

Disqualifiers: Diabetes, Uncontrolled seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether metformin, a drug commonly used for diabetes, can help children with cerebral palsy (CP) improve motor skills and cognitive functions. Participants will take metformin for a period and then stop, allowing researchers to observe any changes in their abilities. Children with CP who haven't recently undergone certain surgeries or experienced metabolic issues, and who can swallow tablets or use a feeding tube, might be suitable candidates. The trial aims to determine if metformin is safe and tolerated in these children. As a Phase 2 trial, this research focuses on assessing metformin's effectiveness in an initial, smaller group of children with CP, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that could interact with metformin, such as diuretics, cationic drugs, and some other specific medications. If you are on any of these, you may need to stop or adjust them before participating.

Is there any evidence suggesting that metformin is likely to be safe for children with cerebral palsy?

Research shows that metformin is generally safe for children. Studies have found no serious problems when children use metformin. Some mild issues, such as an upset stomach, have been reported, but these are not serious.

Reviews of metformin use have uncovered no new safety concerns. The known side effects have not increased in frequency or severity. Additionally, no reports have linked deaths directly to metformin.

While metformin is being tested in this study, previous research suggests it is well-tolerated by young people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cerebral palsy?

Metformin is unique because, unlike traditional treatments for cerebral palsy that primarily focus on managing symptoms through therapies and surgeries, it targets cellular energy processes. Researchers are excited about metformin because it is traditionally used to treat type 2 diabetes by improving insulin sensitivity and has shown potential to influence neural repair and growth. This means metformin might offer a new way to enhance brain function in individuals with cerebral palsy, which could lead to improved motor skills and cognitive abilities. This possible mechanism of promoting neural health makes metformin a promising candidate for changing the way cerebral palsy is managed.

What evidence suggests that metformin might be an effective treatment for cerebral palsy?

Research has shown that metformin, a medication commonly used for diabetes, might offer additional benefits. Early animal studies suggested that metformin can help reduce movement problems after a brain injury. This trial will investigate whether metformin can also aid movement issues in cerebral palsy. Additionally, researchers are studying metformin's potential to improve cognitive function in children. While more research is needed, these findings are promising for using metformin to treat cerebral palsy. ^{1 2 3 5 6}

Who Is on the Research Team?

Darcy Fehlings, MD, MSc

Principal Investigator

Holland Bloorview Kids Rehabilitation Hospital

Are You a Good Fit for This Trial?

Children aged 5-18 with cerebral palsy who can follow simple instructions, have no history of renal disease or severe lung infections, and haven't had recent orthopedic surgery. They must not be on certain other medications, have uncontrolled seizures, heart failure, diabetes, or a known allergy to metformin.

Inclusion Criteria

I haven't had low blood sugar episodes since turning 2 years old.

Informed consent (and assent, where applicable) will be obtained from the participants by study team members authorized to consent for this study

Evidence of WMI or GMI pattern on prior clinical neuro-imaging scanning (MRI)

Exclusion Criteria

I have pernicious anemia.

I haven't had brain scans to check for white or gray matter issues.

I have been treated for heart failure in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase A1

Participants undergo a baseline period with no metformin

16 weeks

Phase B

Participants receive metformin for 16 weeks

16 weeks

7 safety visits

Phase A2

Participants undergo a follow-up period with no metformin

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The trial is testing the safety and how well children stick to taking metformin. It's also looking at whether metformin can improve movement and thinking skills in kids with cerebral palsy. The study has periods without the drug followed by a period with it.

How Is the Trial Designed?

Group I: Metformin Experimental Treatment 1 Intervention

Metformin oral tablet will be taken by mouth or through a gastrostomy tube, once or twice a day for 16 weeks.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Holland Bloorview Kids Rehabilitation Hospital

Lead Sponsor

Trials

69

Recruited

14,100+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03710343

Metformin for Motor and Cognitive Improvement in Children ... The study is exploring whether metformin has possible health benefits for improving motor function and cognition.

2. bmjpaedsopen.bmj.com bmjpaedsopen.bmj.com/content/9/1/e002784

Safety and feasibility trial protocol of metformin in infants ... Metformin is an antidiabetic drug that has shown promise to promote recovery after brain injury, but it has not been widely used in infants or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7218053/

Neuroprotective Effects of Diabetes Drugs for the Treatment of ... It can result in long-term devastating consequences with neurologic complications varying from mild behavioral deficits to severe seizure, ...

4. canchild.ca canchild.ca/resources/303-metformin-and-neural-repair-in-mouse-models-of-cerebral-palsy/

Metformin and Neural Repair in Mouse Models of Cerebral ... Our early studies have shown that animals that receive metformin soon after the brain injury have significantly less motor impairment. This outcome is ...

5. hollandbloorview.ca hollandbloorview.ca/metformin-motor-and-cognitive-improvement-children-cerebral-palsy-feasibility-study

Metformin for Motor and Cognitive Improvement in Children ... We want to conduct a small study to see if it would be possible to do a bigger study that would test the effectiveness of a drug called metformin, ...

6. fda.gov fda.gov/media/181843/download

Riomet Pediatric Postmarketing Safety Review There were no new safety signals identified, no increased severity or frequency of any labeled adverse events, and no deaths directly ...