Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS)

NCT ID: NCT04788745

Last Updated: 2023-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-29
• Study Completion Date: 2023-05-24

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).

Detailed Description

The study will consist of a 4-week lead-in period to obtain a stable baseline measurement of clinical markers of disease and oxidative stress. After the lead-in phase, participants will receive trimetazidine for 12 weeks. Participants will visit the clinic at 6-week intervals, during which we will obtain a blood sample to measure the pharmacodynamic response. We will also collect information regarding the rate of disease progression (i.e. ALSFRS-R and SVC). At weeks 3 and 9 of treatment, participants will conduct a teleconference visit, during which we will collect data on ALSFRS-R. Adverse events will be collected and recorded throughout the entire trial duration. At the end of the on-treatment period, a close-out visit will occur after four weeks. The total study period per participant will be 20 weeks.

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

Trimetazidine 35mg

Group Type: EXPERIMENTAL

Trimetazidine Dihydrochloride

Intervention Type: DRUG

Oral tablet, twice-daily

Interventions

Trimetazidine Dihydrochloride

Oral tablet, twice-daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• injectable
• implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system ( IUS)
• vasectomised partner
• Females of child-bearing potential must have a negative serum pregnancy test at screening and baseline and be non-lactating

• Deprivation of freedom by administrative or court order

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FightMND

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: collaborator

King's College London

OTHER

Sponsor Role: collaborator

Julius Clinical

INDUSTRY

Sponsor Role: collaborator

The University of Queensland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shyuan Ngo, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Queensland

Robert Henderson, MBBS, PhD

Role: PRINCIPAL_INVESTIGATOR

Royal Brisbane & Women's Hospital

Leonard van den Berg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Ammar Al-Chalabi, MB ChB, PhD

Role: PRINCIPAL_INVESTIGATOR

King's College London

Frederik Steyn, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Queensland

Ruben van Eijk, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

Royal Brisbane & Women's Hospital

Brisbane, Queensland, Australia

University Medical Centre Utrecht

Utrecht, , Netherlands

King's College London

London, , United Kingdom

Countries

Australia; Netherlands; United Kingdom

Other Identifiers

MetFlex

Identifier Type: -

Identifier Source: org_study_id