Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000082606
Ethics application status
Approved
Date submitted
15/01/2014
Date registered
22/01/2014
Date last updated
22/01/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot study of the treatment of patients with sporadic Inclusion Body Myositis with the Anaplerotic medication Triheptanoin
Scientific title
Pilot study of the effectiveness of the anaplerotic medication Triheptanoin in improving muscle strength in patients with sporadic Inclusion Body Myositis
Secondary ID [1] 283907 0
nil
Universal Trial Number (UTN)
U1111-1152-1664
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sporadic Inclusion body Myositis 290905 0
Condition category
Condition code
Musculoskeletal 291258 291258 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 291287 291287 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment with the colourless odourless oil Triheptanoin increased as tolerated up to 30% of daily caloric requirement and at least 20% of caloric intake. Triheptanoin will be mixed with food throughout the day and patients will return the empty bottles to ensure compliance. Treatment at full dose will continue for 6 months
Intervention code [1] 288588 0
Treatment: Drugs
Comparator / control treatment
Baselinie assessment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291254 0
Muscle strength - 6 minute walk test. Manual muscle testing of distal and proximal upper and lower limb muscles by standard protocol
Timepoint [1] 291254 0
6 months
Secondary outcome [1] 306348 0
Blood Creatine kinase level
Timepoint [1] 306348 0
6 months
Secondary outcome [2] 306349 0
Muscle MRI of thighs and legs will be assessed qualitatively for signal change and fat content
Timepoint [2] 306349 0
6 months
Secondary outcome [3] 306350 0
Weight change on digital scale
Timepoint [3] 306350 0
6 months
Secondary outcome [4] 306351 0
Assessment of Swallow function using items from the ASSIST tool
Timepoint [4] 306351 0
6 months

Eligibility
Key inclusion criteria
Biopsy proven sporadic Inclusion Body Myositis
Minimum age
30 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inability to walk

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Open label treatment of patients with sIBM
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
24/02/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
3
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 1967 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 7699 0
2139 - Concord Repatriation Hospital

Funding & Sponsors
Funding source category [1] 288548 0
Self funded/Unfunded
Name [1] 288548 0
Country [1] 288548 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Ultragenyx
Address
Ultragenyx, Inc.
60 Leveroni Court, Suite 200
Novato CA 94949
Country
United States of America
Secondary sponsor category [1] 287260 0
None
Name [1] 287260 0
Address [1] 287260 0
Country [1] 287260 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290412 0
Sydney Local Health District Human Research Ethics Committee (CRGH)
Ethics committee address [1] 290412 0
Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139
Ethics committee country [1] 290412 0
Australia
Date submitted for ethics approval [1] 290412 0
Approval date [1] 290412 0
24/10/2013
Ethics approval number [1] 290412 0
HREC/13/CRGH/20

Summary
Brief summary
Sporadic Inclusion body myositis is the most common acquired muscle disorder in patients over the age of 50. The cause of IBM is not known and there is no effective therapy.
IBM is a slowly progressive disorder with increasing weakness and muscle atrophy involving particularly the thighs, long finger flexors and bulbar muscles resulting in progressive loss of mobility, loss of hand function and impaired swallowing. It progresses to disability over 5-10 years with wheel chair dependence, loss of hand function, impaired nutrition due to inability to swallow, increasing debility and susceptibility to aspiration.
Theories for IBM pathogensesis can be divided into primary inflammatory hypotheses and primary degenerative hypotheses. Treating IBM with immunosuppression is not effective and steroids may accelerate the disorder possibly by stimulating catabolic pathways. Degenerative hypotheses can be grouped into several catagories, myofiber injury by beta-amyloid, myofiber injury due to other accumulated molecules, a myonuclear disorder, a disorder of protein degradation and a disorder of mitochondria. The most consistent finding in IBM is an abnormality of protein degradation with accumulation of degradation products in autophagic vacuoles. There is also a deficit in Proteosome 26-ubiquitin protein degradation. The proteosome-ubiquitin and autophagy pathways are activated in the presence of energy depletion and starvation to provide an alternate source of energy to fuel the citric acid cycle and maintain energy homeostasis. It is not certain as to whether there is an acceleration of protein breakdown or a defect of disposal of breakdown products or both in IBM. The crucial protein and organelle disposal pathway of autophagy is critically overloaded and this is probably the most important mechanism for myofibre damage. It is probable that this overloading is the result of catabolic pathway acceleration and this may result from a deficit in energy metabolism leading to activation of the catabolic cascade. Progressive muscle atrophy and increasing weakness indicate the predominance of protein catabolic over anabolic activities in IBM. It is hypothesised that repairing energy deficits and increasing anabolic activity will be beneficial in IBM and will in turn inhibit and “switch off” the harmful autophagic process. Trihepatanoin (TGC7) is a triglyceride containing three C7 fatty acid chains. After cleavage in the gut, heptanoate is absorbed through the gut and can be metabolised in most tissues. As a medium chain fatty acid, uptake into mitochondria is via diffusion and independent from the shuttle system, thereby providing fast energy. Each heptanoate provides both substrate (acyl CoA) and intermediates (oxaloacetate; via carboxylation of propionyl-CoA) for the CAC in muscle and brain. Therefore, TGC7 has the ability to refuel the CAC, increase ATP production and reverse the catabolic cascade.
It is hypothesised that administering Triheptanoin, up to 30% of daily caloric requirement, by fuelling the CAC to enhance anabolic pathways and inhibit catabolism will have a significant benefit in the treatment of IBM to maintain and improve muscle strength and swallowing.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 45558 0
A/Prof Alastair Corbett
Address 45558 0
Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139
Country 45558 0
Australia
Phone 45558 0
612 97676416
Fax 45558 0
Email 45558 0
[email protected]
Contact person for public queries
Name 45559 0
A/Prof Alastair Corbett
Address 45559 0
Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139
Country 45559 0
Australia
Phone 45559 0
612 97676416
Fax 45559 0
Email 45559 0
[email protected]
Contact person for scientific queries
Name 45560 0
A/Prof Alastair Corbett
Address 45560 0
Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139
Country 45560 0
Australia
Phone 45560 0
612 97676416
Fax 45560 0
Email 45560 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.