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Trial registered on ANZCTR

Registration number

ACTRN12618001266257

Ethics application status

Not required

Date submitted

23/07/2018

Date registered

27/07/2018

Date last updated

3/03/2021

Date data sharing statement initially provided

10/07/2019

Date results provided

3/03/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Ketogenic Diet In Inclusion Body Myositis

Scientific title

Ketogenic Diet In Inclusion Body Myositis: A Case Study

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1217-8024

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Inclusion Body Myositis

Condition category

Condition code

Inflammatory and Immune System

Autoimmune diseases

Musculoskeletal

Other muscular and skeletal disorders

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Our patient plans to commence a ketogenic diet in an effort to treat her recently diagnosed inclusion body myositis. She has given us permission to perform assessments on strength, function, quality of life, weight/BMI, imaging, and blood tests at baseline (prior to commencing the diet) and at 1 year after commencing the diet.

We may support her with a face to face nutritionist consult, and ongoing nutritionist support if requested. The patient will buy all food ingredients and conduct the diet herself at her home.

She will be wholly responsible for maintaining her diet; we will simply observe the (possible) effects of the diet on the above outcome measures.

Intervention code [1]

Not applicable

Comparator / control treatment

No control group, case study only.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Composite primary outcome. Strength tests.

Chest press (kg), maximum obtainable with one full repetition on weights machine, assessed by physiotherapist blinded to treatment.
Leg press (kg), maximum obtainable with one full repetition on weights machine, assessed by physiotherapist blinded to treatment.
Lateral pulldown (kg), maximum obtainable with one full repetition on weights machine, assessed by physiotherapist blinded to treatment.
Grip strength (kg), maximum obtainable with one full repetition on hand dynamometer, assessed by physiotherapist blinded to treatment.

Timepoint [1]

1 year.

Primary outcome [2]

Composite primary outcome. Functional tests.

Get up and go tests (seconds), patient stands from a standard chair and walks 3 meters then turns around walks back and sits down again, two trials done (2 minutes rest between each trial) and the average taken as the measurement, assessed by physiotherapist blinded to treatment.
6 minute walk test (seconds), patient walks as far as possible on a flat surface over 6 minutes, two trials done (2 minutes rest between each trial) and the average taken as the measurement, assessed by physiotherapist blinded to treatment.
Stair climb test (seconds), patient walks up and down a flight of stairs, two trials done (2 minutes rest between each trial) and the average taken as the measurement, assessed by physiotherapist blinded to treatment.

Timepoint [2]

1 year,

Primary outcome [3]

Primary outcome. FACIT-F questionnaire, completed by patient in a quiet room.

Timepoint [3]

1 year.

Secondary outcome [1]

Composite secondary outcome. Physical parameters.

Weight (kg), balance scale in clinic.
Body mass index, height measured with measuring tape and weight measured with balance scale, then calculation for body mass index.

Timepoint [1]

1 year.

Secondary outcome [2]

Composite secondary outcome. Lower limb muscle composition.

Leg flexor muscles maximal diameter in cm on MRI.
Leg flexor muscles maximal volume in cm3 on MRI.
Leg flexor fat content in % on MRI.
Changes consistent with inflammation/edema (presence or absence) on MRI.

Timepoint [2]

1 year.

Secondary outcome [3]

Composite secondary outcome. Metabolic markers.

HbA1C (mmol/mol) by serum assay.
Total cholesterol (mmol/L) by serum assay.
Low density lipoprotein (mmol/L) by serum assay.
High density lipoprotein (mmol/L) by serum assay.
Triglycerides (mmol/L) by serum assay.
Creatine kinase (mmol/L) by serum assay.
C-reactive protein (mmol/L) by serum assay.

Timepoint [3]

1 year.

Eligibility

Key inclusion criteria

Female adult, 50 to 60 years of age, diagnosed with definite inclusion body myositis in 2017.

Minimum age

50 Years

Maximum age

60 Years

Sex

Females

Can healthy volunteers participate?

Key exclusion criteria

Not applicable.

Study design

Purpose

Natural history

Duration

Longitudinal

Selection

Convenience sample

Timing

Prospective

Statistical methods / analysis

Not applicable.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

7/08/2018

Actual

7/08/2018

Date of last participant enrolment

Anticipated

7/08/2018

Actual

7/08/2018

Date of last data collection

Anticipated

7/08/2019

Actual

15/08/2019

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Neurology Dept

Address [1]

Waikato Hospital
Pembroke St Hamilton NZ 3204

Country [1]

New Zealand

Primary sponsor type

Individual

Name

Matthew Phillips

Address

Waikato Hospital
Pembroke St Hamilton NZ 3204

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Not required

Ethics committee name [1]

Ethics committee address [1]

Ethics committee country [1]

Date submitted for ethics approval [1]

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Sporadic inclusion body myositis is the most common myopathy in patients over 50 years of age.1 The prevalence of the condition in Australia is 9.3 per 1 million inhabitants; it is relatively rare in non-Caucasians.2,3

Clinically, the most involved muscles are usually the long finger flexors and quadriceps muscles, with the biceps brachii and foot dorsiflexors also commonly afflicted.4 The mean decline in muscle strength is about 5% per year.4,5 Further symptoms of the disease include dysphagia, which occurs in 40 to 80% of patients, as well as global weakness and fatigue.4 In its later stages, inclusion body myositis can result in severe disability, leading to the eventual use of a wheelchair in virtually all patients, and severely reduced quality of life, such that a significant minority opt for euthanasia.5,6

The pathophysiology of inclusion body myositis is incompletely understood, but it appears to involve the coexistence of muscle inflammation and degeneration.3,4 On one hand, inclusion body myositis is characterized by upregulated inflammatory mediators and an aggressive cytotoxic T cell invasion of nonnecrotic muscle fibers.4 On the other hand, it is also characterized by the accumulation of abnormal protein aggregates, many of which have been described in neurodegeneration,6 and mitochondrial structural changes suggestive of mitochondrial dysfunction.4 Moreover, it has been suggested that autophagy, a process responsible for the degradation and recycling of damaged cell components, may be impaired, or even overloaded, in inclusion body myositis.3,4

To date, inclusion body myositis has proven refractory to all known pharmacological treatments; current management focuses on exercise, physical therapy, orthotic devices, and occupational therapy.3 A well-balanced diet has also been suggested as potentially beneficial,4 but to our knowledge, no prospective diet studies in inclusion body myositis have been attempted.

In theory, a high-fat, low-carbohydrate “ketogenic” diet may have beneficial effects in inclusion body myositis. Preliminary evidence from animal studies suggests that such a diet exerts anti-inflammatory effects,7,8 possibly by producing fewer reactive oxygen species and/or by elevating levels of the anti-inflammatory neuromodulator adenosine.7 With respect to muscle fiber degeneration, evidence from animal studies also shows that ketogenic diets may result in increased ATP levels and enhanced mitochondrial biogenesis,8 both of which may alleviate the potential energy shortage produced in the context of mitochondrial dysfunction.

On this background, our objective is to observe the effects of a ketogenic diet in a patient with inclusion body myositis for a period of 1 year, and to determine whether this approach is plausible, safe, and efficacious with respect to strength, function, and quality of life.

References:
(1) Needham M, Corbett A, Day T, et al. Prevalence of sporadic inclusion body myositis and factors contributing to delayed diagnosis. J Clin Neurosci 2008;15:1350-1353.
(2) Phillips BA, Zilko PJ, Mastaglia FL. Prevalence of sporadic inclusion body myositis in Western Australia. Muscle Nerve 2000;23(6):970-972.
(3) Mazen M, Dimachkie MD, Barohn RJ. Inclusion Body Myositis. Semin Neurol 2012;32(3):237-245.
(4) Schmidt K, Schmidt J. Inclusion body myositis: advancements in diagnosis, pathomechanisms, and treatment. Curr Opin Rheumatol 2017;29(6): 632-638.
(5) Cox FM, Titulaer MJ, Sont JK, et al. A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities. Brain 2011;134(Pt 11):3167-3175.
(6) Macado P, Brady S, Hanna MG. Update in inclusion body myositis. Curr Opin Rheumatol 2013;25:763-771.
(7) Masino AS, Ruskin DN. Ketogenic Diets and Pain. J Child Neurol 2013;28(8):993-1001.
(8) Storoni M, Plant GT. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. Mult Scler Int 2015; 2015: 681289.

Trial website

Trial related presentations / publications

Public notes

We have been advised by the Waikato Hospital research coordinator that as an observational study that involves minimal risk to the patient, so long as the patient provides written consent we do not require formal ethics approval.

Contacts

Principal investigator

Name

Dr Matthew CL Phillips

Address

Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204

Country

New Zealand

Phone

+64274057415

Fax

[email protected]

Contact person for public queries

Name

Matthew CL Phillips

Address

Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204

Country

New Zealand

Phone

+64274057415

Fax

[email protected]

Contact person for scientific queries

Name

Matthew CL Phillips

Address

Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204

Country

New Zealand

Phone

+64274057415

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

I have to obtain permission from patient, and it will depend on who is asking. So this could change but for now, no.

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.

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