Amyotrophic Lateral Sclerosis, Motor Neuron Disease
Conditions
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.
Interventions
Oral tablet, twice-daily
Sponsors
FightMND
UMC Utrecht
King's College London
Julius Clinical
The University of Queensland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, single-arm study without placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability | 16 weeks | 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). |
| Level of expression of oxidative stress markers in the plasma and/or serum of trial participants | 16 weeks | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Assessment of the 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) to determine suitability for incorporation into future trial design |
Countries
Australia, Netherlands, United Kingdom
Outcome results
None listed