Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS)

NCT04788745 | Completed Phase 2

• 1 other identifier: MetFlex
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• Sites: 3

Brief Summary

MetFlex is an investigator led, open-label, single-arm, Phase 2a trial to determine the safety and tolerability of trimetazidine for the treatment of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND).

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability

  The occurrence of adverse events, as assessed by Common Terminology Criteria for AEs Version 5, during the 12-week on-treatment period and 4-week wash-out period (16 weeks total).

  16 weeks

• Level of expression of oxidative stress markers in the plasma and/or serum of trial participants

  Expression of oxidative stress markers (malondialdehyde, 8-hydroxy-2'-deoxyguanosine, interleukin-6; assessed by liquid chromatography-mass spectrometry/mass-spectrometry or multiplexing) in the plasma and/or serum of trial participants throughout the treatment period (12-week) and at the end of the wash-out period (4 weeks)

  16 weeks

Secondary Outcomes (1)

• Level of expression of oxidative stress markers in the plasma and/or serum of trial participants to inform future clinical trials in ALS/MND

  16 weeks

Study Arms (1)

Experimental

EXPERIMENTAL

Trimetazidine 35mg

Drug: Trimetazidine Dihydrochloride

Interventions

Trimetazidine Dihydrochloride DRUG

Oral tablet, twice-daily

Experimental

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years
• Signed informed consent prior to the initiation of any study-specific procedures
• Familial or sporadic ALS/MND, defined as clinically possible, probable, or definite as per the El Escorial criteria
• Relative TRICALS risk score between -6.0 to -2.0 (75% of patients with ALS/MND)
• Metabolic index ≥110%, at the screening visit.
• The use of riluzole will be permitted during the study. Individuals taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit.
• Ability to swallow tablets
• Able to lie with torso elevated at a 35° angle for 30 minutes without respiratory support
• Able to give informed consent (as judged by the investigator) and able to comply with all study visits and all study procedures
• Females must not be able to become pregnant (e.g. post-menopausal, surgically sterile or using highly effective birth control methods) for the duration of the study. Highly effective methods of birth control are those with a failure rate of \< 1% per year when employed consistently and correctly, e.g. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• oral
• intravaginal
• transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
• oral

You may not qualify if:

• Unable to provide informed consent
• History of, or current diagnosis of diabetes or medical condition that impacts whole body energy expenditure (e.g. Hashimoto's, heart disease)
• Parkinson's disease or parkinsonism, tremor, restless-leg syndrome
• Safety Laboratory Criteria at screening related to significant kidney disease:
• Creatinine clearance \< 50 mL / min (Cockcroft-Gault) based on Cystatin C
• Tracheostomy or non-invasive ventilation (NIV) use \> 22 hours per day
• Inability to swallow tablets
• Contraindication therapy:
• Allergy for one of the product's active pharmaceutical ingredients (APIs) or excipients.
• Antihypertensive treatment \[Trimetazidine may cause hypotension\]
• Evidence of malignant disease
• Significant neuromuscular disease other than ALS/MND
• Ongoing disease that may cause neuropathy
• Pregnancy or breastfeeding
• Deprivation of freedom by administrative or court order

Sponsors & Collaborators

• The University of Queensland: lead
• FightMND: collaborator
• UMC Utrecht: collaborator
• King's College London: collaborator
• Julius Clinical: collaborator

Study Sites (3)

Royal Brisbane & Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

University Medical Centre Utrecht

Utrecht, Netherlands

Location

King's College London

London, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Trimetazidine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Shyuan Ngo, PhD

  The University of Queensland

  PRINCIPAL INVESTIGATOR

• Robert Henderson, MBBS, PhD

  Royal Brisbane & Women's Hospital

  PRINCIPAL INVESTIGATOR

• Leonard van den Berg, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Ammar Al-Chalabi, MB ChB, PhD

  King's College London

  PRINCIPAL INVESTIGATOR

• Frederik Steyn, PhD

  The University of Queensland

  PRINCIPAL INVESTIGATOR

• Ruben van Eijk, MD, PhD

  UMC Utrecht

  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: Open-label, single-arm study without placebo

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 9, 2021
• Study Start: June 29, 2021
• Primary Completion: May 24, 2023
• Study Completion: May 24, 2023
• Last Updated: July 20, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); AU (1); NL (1)