Back to results

Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS) (MetFlex)

Primary Purpose

Amyotrophic Lateral Sclerosis, Motor Neuron Disease

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Trimetazidine Dihydrochloride

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Royal Brisbane & Women's Hospital
University Medical Centre Utrecht
King's College London

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

Trimetazidine 35mg

Outcomes

Primary Outcome Measures

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).

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)

Secondary Outcome Measures

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

Full Information

NCT ID

NCT04788745

First Posted

March 2, 2021

Last Updated

July 19, 2023

Sponsor

The University of Queensland

Collaborators

FightMND, UMC Utrecht, King's College London, Julius Clinical

1. Study Identification

Unique Protocol Identification Number

NCT04788745

Brief Title

Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS)

Acronym

MetFlex

Official Title

Targeting Metabolic Flexibility in ALS (MetFlex); Safety and Tolerability of Trimetazidine for the Treatment of ALS

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

June 29, 2021 (Actual)

Primary Completion Date

May 24, 2023 (Actual)

Study Completion Date

May 24, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Queensland

Collaborators

FightMND, UMC Utrecht, King's College London, Julius Clinical

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis, Motor Neuron Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Open-label, single-arm study without placebo

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

Trimetazidine 35mg

Intervention Type

Drug

Intervention Name(s)

Trimetazidine Dihydrochloride

Intervention Description

Oral tablet, twice-daily

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability

Description

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).

Time Frame

16 weeks

Title

Level of expression of oxidative stress markers in the plasma and/or serum of trial participants

Description

Time Frame

16 weeks

Secondary Outcome Measure Information:

Title

Level of expression of oxidative stress markers in the plasma and/or serum of trial participants to inform future clinical trials in ALS/MND

Description

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials: