Targeting Metabolic Flexibility in ALS (MetFlex); Safety and Tolerability of Trimetazidine for the Treatment of ALS

Study Purpose:

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).

Study Status:

Not recruiting


Amyotrophic Lateral Sclerosis , Motor Neuron Disease

Study Type:


Type of Intervention:


Intervention Name:

Trimetazidine Dihydrochloride




Phase 2

Study Chair(s)/Principal Investigator(s):

Shyuan Ngo, PhD, The University of Queensland, Robert Henderson, MBBS, PhD, Royal Brisbane & Women's Hospital, Leonard van den Berg, MD, PhD, UMC Utrecht, Ammar Al-Chalabi, MB ChB, PhD, King's College London, Frederik Steyn, PhD, The University of Queensland, Ruben van Eijk, MD, PhD, UMC Utrecht ID:


Neals Affiliated?


Coordinating Center Contact Information

Shyuan Ngo, PhD / email hidden; JavaScript is required / +61734431133

Full Study Summary:

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.

Study Sponsor:

The University of Queensland

Estimated Enrollment:


Estimated Study Start Date:

06 / 29 / 2021

Estimated Study Completion Date:

03 / 31 / 2023

Posting Last Modified Date:

08 / 25 / 2021

Date Study Added to

03 / 09 / 2021

Minimum Age:

18 Years

Maximum Age:

75 Years

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

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

- Females actively seeking to become pregnant who are not using an adequate form of contraceptive as detailed in the Inclusion criteria.

- Deprivation of freedom by administrative or court order

Royal Brisbane & Women's Hospital | Recruiting

Robert Henderson, MBBS, PhD / +617 3646 3111 / email hidden; JavaScript is required

Brisbane, Queensland 4029

University Medical Centre Utrecht | Not yet recruiting

Leonard van den Berg, MD, PhD / +31 88 75 554 94 / email hidden; JavaScript is required


King's College London | Not yet recruiting

Ammar Al-Chalabi, MB ChB, PhD / +44 20 7848 5192 / email hidden; JavaScript is required

United Kingdom