targeting metabolic flexibility in amyotrophic lateral sclerosis (als)

Conditions: Amyotrophic Lateral Sclerosis; Motor Neuron Disease

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).

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.

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 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