Amyotrophic Lateral SclerosisPhase 2MetFlexNCT04788745
Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing Trimetazidine Dihydrochloride in people with Amyotrophic Lateral Sclerosis and Motor Neuron Disease, run by The University of Queensland at 3 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
- What is being tested?
- Trimetazidine Dihydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 29 Jun 2021to 24 May 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Australia1 site
Royal Brisbane & Women's Hospital
Brisbane, Queensland, 4029
About this study
Official title: Targeting Metabolic Flexibility in ALS (MetFlex); Safety and Tolerability of Trimetazidine for the Treatment of ALS
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).
Read the 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.
- Being tested
- Trimetazidine Dihydrochloride
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trimetazidine DihydrochlorideDrug
Oral tablet, twice-daily
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Trimetazidine 35mg Receives: Drug: Trimetazidine Dihydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability
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).
Measured: 16 weeks
Level of expression of oxidative stress markers in the plasma and/or serum of trial participants
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)
Measured: 16 weeks
Secondary outcomes (1)
Level of expression of oxidative stress markers in the plasma and/or serum of trial participants to inform future clinical trials in ALS/MND
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
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2021
- Study start29 Jun 2021
- Primary completion24 May 2023
- Study completion24 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label, single-arm study without placebo
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Queensland
- Sponsor type
- University, hospital or other
- Collaborators
- FightMND, UMC Utrecht, King's College London, Julius Clinical
- Responsible party
- Sponsor
- Investigators
- Shyuan Ngo, PhD, Principal investigator, The University of QueenslandRobert Henderson, MBBS, PhD, Principal investigator, Royal Brisbane & Women's HospitalLeonard van den Berg, MD, PhD, Principal investigator, UMC UtrechtAmmar Al-Chalabi, MB ChB, PhD, Principal investigator, King's College LondonFrederik Steyn, PhD, Principal investigator, The University of QueenslandRuben van Eijk, MD, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04788745
- Sponsor's protocol ID
- MetFlex
- Acronym
- MetFlex
- Status last verified
- Nov 2022
- First submitted
- 2 Mar 2021
- Last updated
- 20 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Metabolic Flexibility in ALS (MetFlex); Safety and Tolerability of Trimetazidine for the Treatment of ALS
- ClinicalTrials.gov ID
- NCT04788745
- Acronym / sponsor ID
- MetFlex / MetFlex
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- The University of QueenslandUniversity, hospital or other
- Collaborators
- FightMND, UMC Utrecht, King's College London, Julius Clinical
- Study start
- 29 Jun 2021 (actual)
- Primary completion
- 24 May 2023 (actual)
- Study completion
- 24 May 2023 (actual)
- First posted
- 9 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label, single-arm study without placebo
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Trimetazidine DihydrochlorideTrimetazidine 35mg |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (16 listed)
- 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:
- Tracheostomy or non-invasive ventilation (NIV) use > 22 hours per day
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trimetazidine DihydrochlorideOral tablet, twice-daily | Drug | Experimental |
Primary outcome
Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability
Time frame: 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
Time frame: 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)
1 secondary outcome
Level of expression of oxidative stress markers in the plasma and/or serum of trial participants to inform future clinical trials in ALS/MND
Time frame: 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shyuan Ngo, PhD principal investigator
The University of Queensland
Robert Henderson, MBBS, PhD principal investigator
Royal Brisbane & Women's Hospital
Leonard van den Berg, MD, PhD principal investigator
UMC Utrecht
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trimetazidine Dihydrochloride in people with Amyotrophic Lateral Sclerosis and Motor Neuron Disease, run by The University of Queensland at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability (time frame: 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.