A Study of Bezafibrate in Mitochondrial Myopathy

NCT02398201 | Completed Phase 2 DMC

• 1 other identifier: 7406
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mitochondrial Diseases

Outcome Measures

Primary Outcomes (1)

• Change in Respiratory Chain Enzyme Activity

  baseline and 12 weeks

Secondary Outcomes (22)

• Change in citrate synthase

  baseline and 12 weeks

• Change in mitochondrial DNA copy number

  baseline and 12 weeks

• Change in COX negative fibres

  baseline and 12 weeks

• Change in serum Fibroblast Growth Factor-21 concentration

  baseline, 3, 6, 9, 12 weeks

• Change in PGC-1alpha concentration

  baseline, 3, 6, 9, 12 weeks

Study Arms (1)

Interventional

EXPERIMENTAL

Bezafibrate tablets (200-600mg) three times daily for 12 weeks.

Drug: Bezafibrate

Interventions

Bezafibrate DRUG

Bezafibrate 200mg-600mg three times daily for 12 weeks.

Also known as: Bezalip

Interventional

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Newcastle-upon-Tyne Hospitals NHS Trust: lead
• Newcastle University: collaborator

Study Sites (1)

Clinical Research Facility, Royal Victoria Infirmary

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

Location

MeSH Terms

Conditions

Mitochondrial Diseases

Interventions

Bezafibrate

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzoates; Acids, Carbocyclic; Chlorobenzoates; Phenyl Ethers; Ethers; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Patrick F Chinnery, MBBS, PhD

  Newcastle Univeristy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2015
• First Posted: March 25, 2015
• Study Start: September 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: March 23, 2017
• Last Updated: September 21, 2017

Record last verified: 2017-09

Locations

GB (1)