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

NCT03710343 | Completed Phase 2 DMC

• 1 other identifier: MET-09-2017
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

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.

Conditions

Cerebral Palsy

Keywords

Cerebral Palsy; Pediatric; Motor Function; GMFCS; Cognitive Function; Metformin

Outcome Measures

Primary Outcomes (5)

• The first indicator of feasibility will be assessed

  Whether 50% of identified eligible potential participants are consented.

  1.25 years

• The second indicator of feasibility will be assessed

  Whether 80% of the study medication (metformin) was taken by all enrolled participants

  1.25 years

• The third indicator of feasibility will be assessed

  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).

  1.25 years

• The fourth indicator of feasibility will be assessed

  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).

  1.25 years

• Tolerability and safety

  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.

  1.25 years

Secondary Outcomes (2)

• 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

• 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

Other Outcomes (5)

• Cambridge Neuropsychological Test Automated Battery (CANTAB)

  Change in CANTAB measures at different from from baseline/pre-intervention (visit 2) to week 16 of Intervention (visit 9) to 48 weeks

• NIH Toolbox (National Institutes of Health)

  Change in NIH toolbox measures from from baseline/pre-intervention (visit 2) to week 16 of Intervention (visit 9) to 48 weeks

• Children's Auditory Verbal Learning Test-2 [CAVLT-2] or Rey Auditory Verbal Learning Test [RAVLT] (depending on age of participant)

  Change in CAVLT-2 measures from from baseline/pre-intervention (visit 2) to week 16 of Intervention (visit 9) to 48 weeks

Study Arms (1)

Metformin

EXPERIMENTAL

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

Drug: Metformin

Interventions

Metformin DRUG

Single case ABA study design. Phase B (intervention period) with metformin administered orally (or by gastrostomy tube) for 16 weeks.

Also known as: Sandoz Metformin FC

Metformin

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Physician diagnosis of cerebral palsy defined "as a group of permanent disorders of the development of movement and posture causing activity limitation that is attributed to non-progressive disturbances that occurred in the developing fetal or infant brain."
• Evidence of WMI or GMI pattern on prior clinical neuro-imaging scanning (MRI)
• No history of hypoglycemia after 2 years of age
• No aspiration pneumonias in the last year requiring hospitalization
• No lower extremity orthopedic surgery in the last six months prior to trial entry
• No acute or chronic metabolic acidosis and/or lactic acidosis over the lifespan, including a lactate level greater than 2.4 mmol/L at the screening visit.
• No history of renal disease
• Age 5 to 18 years, 11 months at the time of enrollment
• Either declare English as their native language or have had at least two years of schooling in English at the time of their baseline assessment
• Gross Motor Function Classification System Level of II - V at the time of enrollment
• Ability to communicate (verbal or non-verbal) pain or discomfort
• With the exception of physiotherapy, no participation in active gross motor rehabilitation treatment (e.g. receiving lower extremity botulinum toxin injections, engaged in robotic walking therapy) up to 4 months prior to trial entry period and willingness to forgo introducing any new CP treatments during the 16 week trial period
• Able to consume whole or crushed tablets swallowed orally or through a gastrostomy tube
• Ability to understand and follow single step instructions/commands (i.e. blinking eyes, opening mouth, and moving head side to side).
• Meet criteria for normal organ function requirements as described below:

You may not qualify if:

• Participants who meet any of the following criteria will not be eligible to take part in the trial:
• No prior clinically ordered neuro-imaging to allow determination of WMI or GMI
• Have a known hypersensitivity to metformin hydrochloride or any of the excipients
• Have Diabetes (Type I or II)
• Have taken oral metformin previously
• Have been part of another clinical intervention study within the past 3 months prior to study entry
• Require sedation for blood tests
• Treatment or planned treatment involving diuretics
• Current or planned treatment with cationic drugs excreted by the kidneys (e.g. amiloride, cimetidine, digoxin, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin).
• Current or planned treatment with concomitant medications with potential unacceptable interaction with metformin including topiramate, lamotrigine, levetiracetam, beta blockers, ACE inhibitors, glycopyrrolate, and carbonic anhydrase inhibitors, or at the discretion of the delegated study physician for medications with potential interactions such as sertraline, lansoprazole and omeprazole.
• Receiving deep brain stimulation or intrathecal baclofen
• Dosage of oral baclofen and benzodiazepines stabilized for less than 2 months prior to study entry, and/or planning to change the dosage over the treatment period (if applicable)
• Females who are pregnant, nursing, or planning a pregnancy during the study
• Pernicious anemia (according to results of the screening visit blood draw)
• Weight for age percentile less than 5%

Sponsors & Collaborators

• Holland Bloorview Kids Rehabilitation Hospital: lead
• The Hospital for Sick Children: collaborator

Study Sites (2)

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Ontario, M4G1R8, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Cerebral Palsy

Interventions

Metformin

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Darcy Fehlings, MD, MSc

  Holland Bloorview Kids Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The trial is designed as a 48 week limited institution two-site single case ABA study feasibility trial.

Study Record Dates

• First Submitted: July 11, 2018
• First Posted: October 18, 2018
• Study Start: November 14, 2023
• Primary Completion: April 11, 2025
• Study Completion: April 24, 2025
• Last Updated: March 2, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)