Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43974   clinical trials with a EudraCT protocol, of which   7312   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Randomised, double-blinded, placebo-controlled, adaptive design trial of the efficacy of acipimox in patients with Mitochondrial Myopathy

    Summary
    EudraCT number
    2018-002721-29
    Trial protocol
    GB  
    Global end of trial date
    21 Dec 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    07 Jun 2023
    First version publication date
    07 Jun 2023
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    08486
    Additional study identifiers
    ISRCTN number
    ISRCTN12895613
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    The Newcastle upon Tyne Hospitals NHS Foundation Trust
    Sponsor organisation address
    Level 1, Regent Point Regent Farm Road, Gosforth, Newcastle upon Tyne, United Kingdom, NE3 3HD
    Public contact
    Gillian Watson, Newcastle Clinical Trials Unit, 0044 0191208813, gillian.watson@newcastle.ac.uk
    Scientific contact
    Gillian Watson, Newcastle Clinical Trials Unit, 0044 01912088813, gillian.watson@newcastle.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 May 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Dec 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Dec 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary outcome is to establish if acipimox can increase energy (ATP content) in skeletal muscle in adult patients with mitochondrial disease and muscle involvement.
    Protection of trial subjects
    None
    Background therapy
    None
    Evidence for comparator
    Patients with mitochondrial disease and muscle involvement will be treated with acipimox or matched placebo to determine what effect treatment has on the ATP content of muscle. Participants will also be treated with low dose aspirin to reduce the incidence of facial flushing, a known side effect of acipimox, and thus to maintain trial blinding.
    Actual start date of recruitment
    07 Jan 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 21
    Worldwide total number of subjects
    21
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    20
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Recruitment was by clinic appointment, interrogation of the Wellcome Centre for Mitochondrial Research Patient Cohort followed by invitation, and advertisement. Cohort patients with mitochondrial disease may be related to one another; to minimise the risk of unblinding, patients with a familial relationship were not screened at the same time.

    Pre-assignment
    Screening details
    Patients’ medical history was viewed, to assess eligibility. Screening procedures: obtaining consent and collection of medical history and information on demographics, medical history, prior procedures and current medication. Eligibility blood samples were taken, and a pregnancy test carried out and contraceptive counselling given, if appropriate.

    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor
    Blinding implementation details
    The trial IMP (acipimox and placebo) were manufactured and packaged to ensure that the participants, PI, Pharmacy staff, clinical team and monitors were blinded to treatment allocation.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Acipimox
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Acipimox
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will be randomised at baseline on to receive either acipimox 250mg or matched placebo PO three times a day (TDS) for 12 weeks. Participants will be advised to take their medication with, or just after, a meal, with the first dose of the day taken 20 – 30 minutes after the nIMP (Section 10.8). No dose modifications are permitted during the treatment period.

    Arm title
    Placebo
    Arm description
    -
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matched placebo capsule, PO, three times daily

    Number of subjects in period 1
    Acipimox Placebo
    Started
    10
    11
    Completed
    6
    6
    Not completed
    4
    5
         Consent withdrawn by subject
    1
    -
         Withdrawn due to COVID-19
    1
    3
         No baseline muscle biopsy
    -
    1
         Unstable baseline muscle biopsy
    2
    1
    Period 2
    Period 2 title
    12 weeks
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Acipimox
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Acipimox
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will be randomised at baseline on to receive either acipimox 250mg or matched placebo PO three times a day (TDS) for 12 weeks. Participants will be advised to take their medication with, or just after, a meal, with the first dose of the day taken 20 – 30 minutes after the nIMP (Section 10.8). No dose modifications are permitted during the treatment period.

    Arm title
    Placebo
    Arm description
    -
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matched placebo capsule, PO, three times daily

    Number of subjects in period 2
    Acipimox Placebo
    Started
    6
    6
    Completed
    6
    6
    Period 3
    Period 3 title
    Change from baseline to 12 weeks
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Acipimox
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Acipimox
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects will be randomised at baseline on to receive either acipimox 250mg or matched placebo PO three times a day (TDS) for 12 weeks. Participants will be advised to take their medication with, or just after, a meal, with the first dose of the day taken 20 – 30 minutes after the nIMP (Section 10.8). No dose modifications are permitted during the treatment period.

    Arm title
    Placebo
    Arm description
    -
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Matched placebo capsule, PO, three times daily

    Number of subjects in period 3
    Acipimox Placebo
    Started
    6
    6
    Completed
    6
    6

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Acipimox
    Reporting group description
    -

    Reporting group title
    Placebo
    Reporting group description
    -

    Reporting group values
    Acipimox Placebo Total
    Number of subjects
    10 11 21
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    10 10 20
        From 65-84 years
    0 1 1
    Gender categorical
    Units: Subjects
        Female
    8 9 17
        Male
    2 2 4

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Acipimox
    Reporting group description
    -

    Reporting group title
    Placebo
    Reporting group description
    -
    Reporting group title
    Acipimox
    Reporting group description
    -

    Reporting group title
    Placebo
    Reporting group description
    -
    Reporting group title
    Acipimox
    Reporting group description
    -

    Reporting group title
    Placebo
    Reporting group description
    -

    Primary: ATP content in muscle at baseline (mean and sd)

    Close Top of page
    End point title
    ATP content in muscle at baseline (mean and sd) [1]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the small number of participants with both baseline and week 12 data for the primary outcome, the analyses are descriptive and no statistical comparison between the placebo and the acipimox groups are made.
    End point values
    Acipimox Placebo
    Number of subjects analysed
    6
    6
    Units: nmol/mg
        arithmetic mean (standard deviation)
    5.47 ( 1.37 )
    4.78 ( 0.74 )
    No statistical analyses for this end point

    Primary: ATP content in muscle at Week 12 (mean and sd)

    Close Top of page
    End point title
    ATP content in muscle at Week 12 (mean and sd) [2]
    End point description
    End point type
    Primary
    End point timeframe
    12 weeks
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the small number of participants with both baseline and week 12 data for the primary outcome, the analyses are descriptive and no statistical comparison between the placebo and the acipimox groups are made.
    End point values
    Acipimox Placebo
    Number of subjects analysed
    6
    6
    Units: nmol/mg
        arithmetic mean (standard deviation)
    4.51 ( 1.13 )
    4.91 ( 1.24 )
    No statistical analyses for this end point

    Primary: Change in ATP content in muscle from baseline to Week 12 (mean and sd)

    Close Top of page
    End point title
    Change in ATP content in muscle from baseline to Week 12 (mean and sd) [3]
    End point description
    End point type
    Primary
    End point timeframe
    Change from baseline to 12 weeks
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the small number of participants with both baseline and week 12 data for the primary outcome, the analyses are descriptive and no statistical comparison between the placebo and the acipimox groups are made.
    End point values
    Acipimox Placebo
    Number of subjects analysed
    6
    6
    Units: nmol/mg
        arithmetic mean (standard deviation)
    -0.97 ( 1.47 )
    0.128 ( 1.618 )
    No statistical analyses for this end point

    Primary: ATP content in muscle at baseline (median and range)

    Close Top of page
    End point title
    ATP content in muscle at baseline (median and range) [4]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the small number of participants with both baseline and week 12 data for the primary outcome, the analyses are descriptive and no statistical comparison between the placebo and the acipimox groups are made.
    End point values
    Acipimox Placebo
    Number of subjects analysed
    6
    6
    Units: nmol/mg
        median (full range (min-max))
    5.47 (3.27 to 7.17)
    4.86 (3.46 to 5.54)
    No statistical analyses for this end point

    Primary: ATP content in muscle at Week 12 (median and range)

    Close Top of page
    End point title
    ATP content in muscle at Week 12 (median and range) [5]
    End point description
    End point type
    Primary
    End point timeframe
    12 weeks
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the small number of participants with both baseline and week 12 data for the primary outcome, the analyses are descriptive and no statistical comparison between the placebo and the acipimox groups are made.
    End point values
    Acipimox Placebo
    Number of subjects analysed
    6
    6
    Units: nmol/mg
        median (full range (min-max))
    4.73 (2.72 to 5.79)
    4.81 (3.3 to 6.94)
    No statistical analyses for this end point

    Primary: Change in ATP content in muscle from baseline to Week 12 (median and range)

    Close Top of page
    End point title
    Change in ATP content in muscle from baseline to Week 12 (median and range) [6]
    End point description
    End point type
    Primary
    End point timeframe
    Change from baseline to 12 weeks
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the small number of participants with both baseline and week 12 data for the primary outcome, the analyses are descriptive and no statistical comparison between the placebo and the acipimox groups are made.
    End point values
    Acipimox Placebo
    Number of subjects analysed
    6
    6
    Units: nmol/mg
        median (full range (min-max))
    -0.565 (-2.87 to 0.55)
    0.395 (-2.24 to 2.33)
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events are reported as they happen, throughout the trial.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    2.1
    Reporting groups
    Reporting group title
    Acipimox
    Reporting group description
    -

    Reporting group title
    Placebo
    Reporting group description
    -

    Serious adverse events
    Acipimox Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Acipimox Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 10 (90.00%)
    10 / 11 (90.91%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Burning sensation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Impaired healing
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Peripheral swelling
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Chest pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Choking
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Dyspnoea
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 11 (27.27%)
         occurrences all number
    0
    2
    Oropharyngeal pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Sinonasal obstruction
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood magnesium decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Fall
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Head injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Wound haemorrhage
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 10 (10.00%)
    5 / 11 (45.45%)
         occurrences all number
    1
    4
    Hypoaesthesia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Eye disorders
    Blepharitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Dyspepsia
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    Eructation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Nausea
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    Vomiting
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Contusion
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    Dermatitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Dermatitis contact
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Hypoaesthesia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Skin discolouration
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Myopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Alveolar osteitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Bacterial vaginosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    COVID-19
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 11 (9.09%)
         occurrences all number
    2
    1
    Oral infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Post-acute COVID-19 syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    Urinary tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Aug 2019
    Substantial Amendment 01 This amendment relates to two additional documents not previously submitted as part of the initial REC approval process. These documents include: • AIMM Sleep Wake Diary (attached) – This is a diary to be used for the subset of participants who will undergo activity monitoring as part of the trial. It is detailed in the approved trial protocol but was not included in the original application • Pregnancy Follow-up Consent Form - To formally obtain consent for follow-up for trial participants or their partner should a pregnancy occur during their participation in the trial
    08 Jul 2020
    Substantial Amendment 02 Inclusion criteria updated to include patients (≥ 16 years) with clinician-confirmed, genetically proven mitochondrial myopathy. Protocol, PIS, Brief PIS and Lily wording adverts updated to reflect change Assay analysis of primary outcome measure changed following assay validation work Secondary outcome measure of cycle ergometry made optional due to COVID-19 and access to facilities Frequency of follow-up phone calls reduced from weekly to Weeks 1, 2, 4 and 8, and optional at Week 10 Options for participants wishing to withdraw from trial or from active treatment clarified and refined to withdrawal from active treatment with continued follow-up by trial team, or withdrawal with no further data collection; protocol updated and Participant Withdrawal Form and Discontinuation of Treatment Form created Protocol updated to allow use of routine bloods taken in previous three months period to be used for screening, to minimise visit length participant burden Protocol updated to provide more contraceptive guidance for participants and their partners while on the trial Protocol updated to include signposting of participants via Patient Identifying Centres (PICs) Staffing and contact detail changes: • Protocol, GP letter, Hospital Consultant letter, Thank you letters, invitation letter and consent form - Update of Chief Investigator’s title and role • Protocol updated to include: additional trial management and data management staff, updated Sponsor Pharmacy email and Sponsor address, and to remove Prof Turnbull as a Co-investigator Information sheets created to provide participants with information prior to, and following, muscle biopsy Pregnant Partner Information sheet created to provide information formally to a pregnant partner of a trial participant, prior to obtaining their consent for pregnancy follow-up and to accompany previously approved Consent to Follow up Form
    16 Dec 2020
    Substantial Amendment 03 Dr Naomi Thomas replaced Professor Gráinne Gorman as Principal Investigator at the single trial site PIC Site Invitation Letter created for PIC sites to give to potential participants Patient Information Sheet, brief Patient Information Sheet, invitation letter and adverts updated to correct timings of follow-up phone calls
    11 Jun 2021
    Substantial Amendment 04 Change of Trial Manager Transfer of Physical Examination and assessment of Vital Signs from Baseline to Screening Addition of Oxygen saturations to Vital Signs tests ECG only to be performed in patients undergoing exercise testing Removal of laboratory analyses in trial protocol: Investigation of potential molecular markers of mitochondrial biogenesis, and metabolomic analysis to identify novel biomarkers in blood and urine Alteration of laboratory analyses: use of an assay kit forNAD+/NADH ratio via metabolomics in muscle, and quantitative proteomics analysis made optional Correction of typographical errors in protocol Addition of box for witness details to Informed Consent Form, and amendment of wording in Patient Information Sheet and protocol to allow for oral consent, with independent witnessing and signature of the Consent Form, for patients with weakness/ataxia due to their condition Addition of information relating to site procedures to manage potential non-availability of web-based randomisation system Change of individual performing expectedness assessment of SARs, due to change in Sponsor process Avoidance of unblinding during recruitment process, in this cohort of patients Update to Contraception Guidance to include exclusively same-sex relationships Protocol updated to state that eligibility bloods analysed in Newcastle Laboratories in previous three months are acceptable for screening Clarification of which staff members can carry out follow-up phone calls Separation of Chief Investigator (CI) and Principal Investigator (PI) responsibilities Addition of information relating to filing withdrawal forms at site Clarification of: SAE, site pregnancy reporting, and Statistics procedures, and timing of dispensing and fitting of wearable activity monitor, and provision of sleep-wake diary
    29 Jul 2021
    Substantial Amendment 05 This amendment was submitted for the formal halt of trial recruitment. A temporary recruitment pause was necessary as the trial IMP reached the end of its shelf life as a result of COVID-19 and delays to the second IMP campaign.
    02 Dec 2021
    Substantial Amendment 06 Change of definition of end of trial, from Last Patient Last Visit (LPLV) date, to date of last data collection for last participant.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    16 Mar 2020
    The interruption involved the withdrawal from trial treatment of the five participants that were participating at the trial at the time. The interruption was due to the COVID-19 pandemic, and the decision was made in the best interests of the participants, as mitochondrial patients are considered vulnerable and as such, at the time, were subject to shielding measures.
    01 Dec 2020

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA