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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]

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

Condition category

Condition code

Musculoskeletal

Other muscular and skeletal disorders

Inflammatory and Immune System

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]

Treatment: Drugs

Comparator / control treatment

Baselinie assessment

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Muscle strength - 6 minute walk test. Manual muscle testing of distal and proximal upper and lower limb muscles by standard protocol

Timepoint [1]

6 months

Secondary outcome [1]

Blood Creatine kinase level

Timepoint [1]

6 months

Secondary outcome [2]

Muscle MRI of thighs and legs will be assessed qualitatively for signal change and fat content

Timepoint [2]

6 months

Secondary outcome [3]

Weight change on digital scale

Timepoint [3]

6 months

Secondary outcome [4]

Assessment of Swallow function using items from the ASSIST tool

Timepoint [4]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Concord Repatriation Hospital - Concord

Recruitment postcode(s) [1]

2139 - Concord Repatriation Hospital

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Local Health District Human Research Ethics Committee (CRGH)

Ethics committee address [1]

Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

24/10/2013

Ethics approval number [1]

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

A/Prof Alastair Corbett

Address

Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139

Country

Australia

Phone

612 97676416

Fax

[email protected]

Contact person for public queries

Name

Alastair Corbett

Address

Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139

Country

Australia

Phone

612 97676416

Fax

[email protected]

Contact person for scientific queries

Name

Alastair Corbett

Address

Concord Repatriation General Hospital
Hospital Road
Concord NSW 2139

Country

Australia

Phone

612 97676416

Fax

[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

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No additional documents have been identified.

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