Targeting metabolic flexibility in ALS (MetFlex); safety and tolerability of trimetazidine for the treatment of ALS;An investigator initiated and conducted, multicentre, international, open-label Phase 2a trial to determine the safety and tolerability of trimetazidine for the treatment of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND)
- Conditions
- amyotrophic lateral sclerosis (ALS)motor neuron disease (MND)10029317
- Registration Number
- NL-OMON52162
- Lead Sponsor
- niversity of Queensland
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
• 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,
probable laboratory supported or definite as per the El Escorial criteria
• Relative TRICALS risk score between -6.0 to -2.0 (75% of patients with
ALS/MND)
• 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 highley effective birth control methods) for the duration of
the study.
• Females of child-bearing potential must have a negative serum pregnancy test
at screening and baseline and be non-lactating
• 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 (Cockroft-Gault) based on Cystatin C
• Tracheostomy or non-invasive ventilation (NIV) use > 22 hours per day
• Contraindication therapy:
Allergy for one of the product*s API*s or expedients.
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
• Deprivation of freedom by administrative or court order
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoints are safety and tolerability of trimetazidine, and the<br /><br>change from baseline of oxidative stress markers.<br /><br>The safety and tolerability of trimetazidine will be determined by examining<br /><br>the toxicities and AEs that are attributable to treatment. The safety<br /><br>parameters will include an assessment of clinical signs and symptoms from the<br /><br>history and physical exam, vital signs, AEs, and laboratory findings (e.g.<br /><br>liver and kidney function).<br /><br>The change from baseline of oxidative stress markers will be determined by<br /><br>quantitative analyses of plasma and/or serum samples by liquid chromatography-<br /><br>mass spectrometry/mass-spectrometry (LC-MS/MS) and/or multiplex analysis of<br /><br>selected targets of interest: IL-6, MDA, 8-OhdG. </p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary endpoints are:<br /><br>• Change from baseline in energy expenditure, based on a composite outcome of<br /><br>body composition and predicted energy expenditure, and measured energy<br /><br>expenditure, following administration of trimetazidine.<br /><br>• Pharmacodynamic properties of oxidative stress markers (IL-6, MDA, and<br /><br>8-OhdG) following administration of trimetazidine</p><br>