Mitochondrial Diseases Clinical Trial
Official title:
A Feasibility Study of Bezafibrate in Mitochondrial Myopathy
Verified date | September 2017 |
Source | Newcastle-upon-Tyne Hospitals NHS Trust |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to gather preliminary data on whether bezafibrate can improve
cellular energy production in mitochondrial disease.
Mitochondrial diseases are rare inherited disorders that arise due to deficient energy
production within the cells of the body. Consequently, the typical clinical features arise in
organs with high energy requirements. Mitochondrial disorders exhibit highly variable
clinical effects, both between individuals and within families. Characteristic symptoms
include muscle weakness (myopathy), hearing loss, migraine, epilepsy and stroke like episodes
in addition to diabetes and heart problems. Mitochondrial disorders can therefore impact
considerably on both quality of life and life expectancy. Despite this, no proven disease
modifying treatments are available.
Pre-clinical studies have identified that several existing medications improve mitochondrial
function. Of these, bezafibrate has the best supportive data and, because it is already
licensed as a treatment for high blood fats, has a well characterised side effect profile.
The investigators will therefore conduct a feasibility study of bezafibrate in people with
mitochondrial myopathy. Ten affected participants will be recruited and will receive a
titrating course of bezafibrate three times daily for 12 weeks.
Status | Completed |
Enrollment | 6 |
Est. completion date | March 23, 2017 |
Est. primary completion date | January 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 64 Years |
Eligibility |
INCLUSION CRITERIA: - The participant is willing and able to given informed consent for participation - Confirmed mt.3243A>G mutation - Evidence of myopathy - Stable dose of current regular medication for at least 4 weeks prior to trial entry - Not already taking fibrates - No evidence of liver impairment - Normal renal function with a creatine clearance of >60ml/minute - In the investigator's opinion is willing and able to comply with all trial requirements - Willingness to allow General Practitioner and Hospital Consultant to be notified of participation in the trial EXCLUSION CRITERIA: - contraindication to MRI scanning - Unstable or poorly controlled diabetes, as determined by the investigator. Participants assigned to group 2 dosing with diabetes (insulin or non-insulin dependent) or glucose intolerance who are unwilling or unable to monitor blood glucose levels during the 12 week treatment period - Previous episode of rhabdomyolysis - History of sensitivity to fibrates - History of gallbladder disease (with or without cholelithiasis) - Liver impairment or disease - Alcohol misuse - Nephrotic syndrome - Untreated hypothyroidism - Use of other medication interacting with bezafibrate - A female participant who is pregnant, lactating or planning pregnancy during the course of the trial; or a male participant who is planning to conceive with their female partner. - Elective or emergency surgery in the 12 weeks prior to screening visit - Scheduled elective surgery or other procedures requiring general anaesthesia during the trial - Any other significant disease or disorder which, in the opinion of the investigator, may put the participant at risk; may influence the result of the trial; or will compromise the individual's ability to participate in the trial. - Participants who have taken part in another research trial involving an investigational medicinal product in the last 12 weeks. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Clinical Research Facility, Royal Victoria Infirmary | Newcastle upon Tyne | Tyne and Wear |
Lead Sponsor | Collaborator |
---|---|
Newcastle-upon-Tyne Hospitals NHS Trust | Newcastle University |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in Respiratory Chain Enzyme Activity | baseline and 12 weeks | ||
Secondary | Change in citrate synthase | baseline and 12 weeks | ||
Secondary | Change in mitochondrial DNA copy number | baseline and 12 weeks | ||
Secondary | Change in COX negative fibres | baseline and 12 weeks | ||
Secondary | Change in serum Fibroblast Growth Factor-21 concentration | baseline, 3, 6, 9, 12 weeks | ||
Secondary | Change in PGC-1alpha concentration | baseline, 3, 6, 9, 12 weeks | ||
Secondary | Change in micro-RNA expression pattern | baseline, 3, 6, 9, 12 weeks | ||
Secondary | Change in cardiac 31P-MRS | We will specifically analyse ATP production and muscle phosphocreatine pre and post bezafibrate | baseline and 12 weeks | |
Secondary | Change in cardiac cine MRI | We will analyse LV (left ventricular) torsion pre and post bezafibrate | baseline and 12 weeks | |
Secondary | Change in skeletal muscle 31P-MRS | We will analyse ATP production, muscle phosphocreatine, t1/2 PCR (phosphocreatine), muscle lipid content and volume. | baseline and 12 weeks | |
Secondary | Change in IPAQ (international physical activity questionnaire) score | baseline, 6 and 12 weeks | ||
Secondary | Change in accelerometry | baseline, 6 and 12 weeks | ||
Secondary | Change in Timed Up and Go (TUG) time | baseline, 6 and 12 weeks | ||
Secondary | Change in NMDAS (Newcastle Mitochondrial Disease Adult Scale) score | baseline, 6 and 12 weeks | ||
Secondary | Change in heteroplasmy level | measured in blood, urine and muscle | baseline and 12 weeks | |
Secondary | Change in NMQ (Newcastle Mitochondrial Disease Quality of Life) Score | baseline, 6 and 12 weeks | ||
Secondary | Change in Fatigue Impact Scale score | baseline, 6 and 12 weeks | ||
Secondary | Number of Adverse Events | Adverse events will be captured every week with opportunistic capture between visits as required. | 0,1,2,3,4,5,6,7,8,9,10,11,12,13,14 weeks | |
Secondary | Change in Full Blood Count | White cell count; Haemoglobin; Platelet count | 0,1,2,3,4,5,6,7,8,9,10,11,12 weeks | |
Secondary | Change in Urea & Electrolytes | Sodium; Potassium; Urea; Creatinine; | 0,1,2,3,4,5,6,7,8,9,10,11,12 weeks | |
Secondary | Change in Liver Function Tests | Alkaline Phosphatase, Alanine Transferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | 0,1,2,3,4,5,6,7,8,9,10,11,12 weeks | |
Secondary | Change in Creatine Kinase | 0,1,2,3,4,5,6,7,8,9,10,11,12 weeks | ||
Secondary | Change in Prothrombin Time | 0,1,2,3,4,5,6,7,8,9,10,11,12 weeks |
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