Patients suffering from amyotrophic lateral sclerosis (ALS)
Conditions
Interventions
Trade Name: Vastarel
Product Name: Trimetazidine
Product Code: 201600930
Pharmaceutical Form: Tablet
Sponsors
The University of Queensland
Eligibility
Sex/Gender
All
Inclusion 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, 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) - Metabolic index (defined as measured resting energy expenditure as a % of predicted resting energy expenditure) =110%, averaged over the lead-in period. - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: - 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 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 - 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 |
|---|---|
| Main Objective: To determine: - The safety and tolerability of trimetazidine in patients with ALS/MND - The change from baseline in oxidative stress markers in patients with ALS/MND after the initiation of trimetazidine - The change from baseline in energy expenditure in patients with ALS/MND after the initiation of trimetazidine - The preliminary pharmcodynamic properties of trimetazidine on oxidative stress markers in patients with ALS/MND - Exploratory associations of the effect of trimetazidine on oxidative stress markers relative to clinical features of hypermetabolism (increased energy expenditure) in patients with ALS/MND - Exploratory associations of the effect of trimetazidine on oxidative stress markers relative to clinical markers of disease progression (e.g.ALSFRS-R and SVC) in patients with ALS/MND This study will provide evidence for the contribution of increased energy expenditure in the pathophysiology of ALS/MND. It will also assess the preliminary effect of trimetazidine.;Secondary Objective: The exploratory endpoints are: - The association between oxidative stress markers (IL-6, MDA, and 8-OHdG) and clinical features of hypermetabolism (i.e. measured resting energy expenditure relative to predicted resting energy expenditure). - The association between oxidative stress markers (IL-6, MDA, and 8-OHdG) and clinical markers of disease progression including ALSFRS-R and SVC (% predicted according to GLI-2012 reference standard).;Primary end point(s): The primary endpoints are safety and tolerability of trimetazidine, and the change from baseline of oxidative stress markers. The safety and tolerability of trimetazidine will be determined by examining the toxicities and AEs that are attributable to treatment. The safety parameters will include an assessment of clinical signs and symptoms from the history and physical exam, vital signs, AEs, and laboratory findings (e.g. liver and kidney function). The change from baseline of oxidative stress markers wi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: - Change from baseline in energy expenditure, based on a composite outcome of body composition and predicted energy expenditure, and measured energy expenditure, following administration of trimetazidine. - Pharmacodynamic properties of oxidative stress markers (IL-6, MDA, and 8-OhdG) following administration of trimetazidine.;Timepoint(s) of evaluation of this end point: - 4-week (28 days) lead-in period to obtain a stable baseline measurement of ALS/MND-related oxidative stress markers (IL-6, MDA, and 8-OHdG), clinical markers of disease (ALSFRS-R and SVC), and to assess that measured energy expenditure is =110% of predicted resting energy expenditure. - 12-week (84 days) on-treatment phase. We will obtain a blood sample to measure the pharmacodynamic response. We will also collect information regarding the ALSFRS-R and SVC and perform assessments to evaluate alterations in energy expenditure. At weeks 3 and 9, we will conduct a teleconference with patients to collect ALSFRS-R score, and inquire about AEs/SAEs. - 4-week (28 days) wash-out with a close-out visit planned for 28 days after the last dose of the study drug. | — |
Countries
Australia, Netherlands
Contacts
Public ContactALS Centrum Nederland
University Medical Centre Utrecht
Outcome results
None listed