Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS)

• Status: Recruiting
• Trial end date: 2023-03-31
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The University of Queensland
• Collaborators: FightMND; Julius Clinical, The Netherlands; King's College London; UMC Utrecht
• Treatments: Trimetazidine

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

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