Mitochondrial myopathy Nervous System Diseases
Conditions
Interventions
This is a randomised, double-blinded, placebo-controlled trial using an adaptive design model that will allow modification of the number of patients needed, as more information is collected. Randomisa
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This single centre trial will take place over 16 weeks per participant. Participants will take a tablet of trial medication three times a day for a period of 12 weeks. Half o
Sponsors
The Newcastle Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must be able to provide full informed consent 2. Male or female patients = 16 years of age 3. Patients must fulfil the following: 3.1. Genetically proven diagnosis of m.3243A>G mutation or single large-scale mtDNA deletion, and 3.2. Evidence of myopathy as confirmed by the investigator 4. Able and willing, in the opinion of the investigator, to comply with all trial requirements 5. Willing for their GP and Specialist (if applicable), to be informed of their participation in the trial 6. Be on a stable dose of any current regular medication for at least four weeks prior to trial entry.
Exclusion criteria
Exclusion criteria: 1. Patients who are currently participating or have participated in a clinical trial of an investigational medicinal product within the 12-week period prior to the date of informed consent 2. Patients who have had an elective or emergency admission to hospital within the 4-week period prior to the date of informed consent 3. Patients with other known uncontrolled medical problems, which, in the opinion of the investigator, would preclude participation in the trial 4. Patients who are: 4.1. Pregnant 4.2. Breastfeeding 4.3. Of childbearing potential with a positive urine pregnancy test prior to starting trial IMP 4.4. Male or female of childbearing potential unwilling to use a double barrier method of contraception throughout the trial (postmenopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential) 5. Patients with moderate to severe renal impairment (creatinine clearance = 300 mg OD) aspirin or other anticoagulant medications which in the opinion of the investigator precludes entry into the trial. Patients receiving high-dose aspirin who are able to come off aspirin for a period of 72 hours prior to any muscle biopsy sample will be eligible to participate 11. Patients with a medical history which in the opinion of the investigator contraindicates the use of low-dose aspirin 12. Patients who are already taking acipimox 13. Patients with an elective hospital admission scheduled during the trial period, which in the opinion of the investigator would preclude participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ATP content in skeletal muscle will be measured from biopsy specimens using a luminescence assay at baseline and 12 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Health-related Quality of life: 1.1. Experiences of physical, mental, and social effects measured using the Quality of Life in Neurological Disorders (NeuroQol) at baseline and 12 weeks. 1.2. Mitochondrial disease-specific health related Quality of Life measured using the Newcastle Mitochondrial Quality of life questionnaires (NMQ) at baseline and 12 weeks. 1.3. Pain measure by the Visual Analog Scale (VAS) at baseline and 12 weeks. 2. Reported perceived fatigue: 2.1. Levels of fatigue measured using the Fatigue Impact Scale (FIS) at baseline and 12 weeks. 2.2. Impact and severity of fatigue measured using the Fatigue Severity Scale (FSS) at baseline and 12 weeks. 3. Symptom-limited cardiopulmonary fitness - This will include assessment of respiratory, cardiovascular and metabolic variables at rest, during and/or exhaustion (peak) 3.1. VO2, VCO2, Anaerobic Threshold (AT), Pulmonary Ventilation (VE), Respiratory Exchange Ratio (RER), and Breathing Frequency (f) via breath-by-breath indirect calorimetry measured by cycle ergometer at baseline and 12 weeks. 3.2. Work rate (Power, measured in watts) measured by cycle ergometer at baseline and 12 weeks. 3.3. Heart Rate (HR), Stroke Volume (SV), Cardiac Output (Q), and Arteriovenous Oxygen Difference (a-VO2 diff) via non-invasive bioreactance cardiac output measured by cycle ergometer at baseline and 12 weeks. 3.4. Rate of Perceived Exertion measured by cycle ergometer at baseline and 12 weeks. 3.5. Blood lactate measured by ear prick or blood test at baseline and 12 weeks. 4. Disease burden measured using the Newcastle Mitochondrial Disease Adult Scale (NMDAS) at baseline and 12 weeks. 5. Upper and lower limb function, balance and walking 5.1. Upper limb function measured by 9-Hole | — |
Countries
England, United Kingdom
Outcome results
None listed