Metformin for Motor and Cognitive Improvement in Children With Cerebral Palsy: A Feasibility Study

Phase 2

Active, not recruiting

• Conditions: Cerebral Palsy
• Interventions: Drug: Metformin

• Registration Number: NCT03710343
• Lead Sponsor: Holland Bloorview Kids Rehabilitation Hospital

Brief Summary

The study design is a single-subject ABA clinical trial that is investigating the feasibility including adherence, safety and tolerability of metformin in children aged 5 to 18 years with cerebral palsy (CP). ABA refers to Phase A1 with no metformin, Phase B with metformin, and Phase A2 with no metformin. Secondarily, the study is exploring whether metformin has possible health benefits for improving motor function and cognition.

Detailed Description

The trial is designed as a 48 week limited institution two-site single case ABA study feasibility trial. ABA refers to Phase A1 with no metformin, Phase B with metformin, and Phase A2 with no metformin. Primary endpoints are feasibility, including recruitment, adherence to study medication and outcome measure completion, safety and tolerability of metformin. Key secondary endpoints are gross motor function and sustainability of intervention. Exploratory endpoints are cognitive and MRI measures as well as qualitative information regarding barriers to participation.

All participants will receive the study drug (metformin) during the 16 week intervention period.

This study will be done at two different locations in Toronto 1) Holland Bloorview Kids Rehabilitation Hospital and 2) the Hospital for Sick Children (SickKids). Each participant will be asked to go to both hospitals to do different tests and assessments for the study. Ten participants with physician diagnosis of CP age 5 to 18 with evidence of white matter imaging (WMI) or Grey Matter Imaging (GMI), and gross motor function classification system (GMFCS) levels II-V will be recruited for participation. MRI, cognitive testing and focus groups will be conducted at SickKids where paediatric protocols and processes have been developed.

Study Timeline

• Study First Submitted: 2018-07-11
• Study First Submitted QC: 2018-10-15
• Study First Posted: 2018-10-18
• Study Start: 2023-11-14
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-13
• Last Update Posted: 2024-05-14
• Primary Completion: 2025-01-31
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
The third indicator of feasibility will be assessed	1.25 years	Whether the GMFM-66 was performed for 80% of participants at all time points: pre-pre intervention , pre-intervention, post-intervention and at follow up (4 months post-intervention).
The fourth indicator of feasibility will be assessed	1.25 years	Whether an MRI was performed for 70% of participants at pre-intervention (i.e. beginning of the 16 week-intervention) and post-intervention (i.e. at the end of the 16-week intervention).
Tolerability and safety	1.25 years	Tolerability and safety of metformin will be evaluated with adverse event reporting and by semi-structured interviews of participants' perceptions of the study procedures known as the Safety Monitoring Uniform Research Form (SMURF) during the 16-week intervention period at all 7 safety visits.
The first indicator of feasibility will be assessed	1.25 years	Whether 50% of identified eligible potential participants are consented.
The second indicator of feasibility will be assessed	1.25 years	Whether 80% of the study medication (metformin) was taken by all enrolled participants

Secondary Outcome Measures

Name	Time	Method
Gross Motor Function Measure-66	Change in Gross Motor Function Measure-66 (GMFM-66) from pre-pre Intervention (visit 1) to baseline/pre-Intervention (visit 2) to week 16 of Intervention (visit 9) to 48 weeks	Gross motor function as assessed by the Gross Motor Function Measure-66 (GMFM-66).
Change in spasticity as measured by the Modified Tardieu Scale from baseline/pre-intervention (visit 2) to 48 weeks	Change in Modified Tardieu Scale (MTS) measure from baseline/pre-intervention (visit 2) to week 16 of Intervention (visit 9) to 48 weeks	Measured by the Modified Tardieu Scale (MTS), which consists of performing a passive muscle stretch at two velocities, slow and fast. The rater measures the angle of the spastic catch in the fast stretch (defined as R1) and then measures the passive range of motion during the slow stretch (defined as R2) in the ankle plantar flexors and knee flexors bilaterally. The difference between R2 and R1 will be the measure of the dynamic component of spasticity. Results are presented on a scale ranging from 0-4 where decreased scores indicate less resistance, which is considered to be a better outcome.

Trial Locations

Locations (2)

Holland Bloorview Kids Rehabilitation Hospital; 🇨🇦 Toronto, Ontario, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada