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

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