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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
10/07/2019
Date data sharing statement initially provided
10/07/2019
Date results information initially provided
10/07/2019
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] 295620 0
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 308949 0
Condition category
Condition code
Inflammatory and Immune System 307881 307881 0 0
Autoimmune diseases
Musculoskeletal 307882 307882 0 0
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] 301925 0
Not applicable
Comparator / control treatment
No control group, case study only.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306821 0
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] 306821 0
1 year.
Primary outcome [2] 306852 0
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] 306852 0
1 year,
Primary outcome [3] 306853 0
Primary outcome. FACIT-F questionnaire, completed by patient in a quiet room.
Timepoint [3] 306853 0
1 year.
Secondary outcome [1] 349941 0
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] 349941 0
1 year.
Secondary outcome [2] 349942 0
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] 349942 0
1 year.
Secondary outcome [3] 349943 0
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] 349943 0
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
Gender
Females
Can healthy volunteers participate?
No
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
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 10675 0
New Zealand
State/province [1] 10675 0

Funding & Sponsors
Funding source category [1] 300200 0
Hospital
Name [1] 300200 0
Neurology Dept
Address [1] 300200 0
Waikato Hospital
Pembroke St Hamilton NZ 3204
Country [1] 300200 0
New Zealand
Primary sponsor type
Individual
Name
Matthew Phillips
Address
Waikato Hospital
Pembroke St Hamilton NZ 3204
Country
New Zealand
Secondary sponsor category [1] 299605 0
None
Name [1] 299605 0
Address [1] 299605 0
Country [1] 299605 0

Ethics approval
Ethics application status
Not required
Ethics committee name [1] 301026 0
Ethics committee address [1] 301026 0
Ethics committee country [1] 301026 0
Date submitted for ethics approval [1] 301026 0
Approval date [1] 301026 0
Ethics approval number [1] 301026 0

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 85634 0
Dr Matthew CL Phillips
Address 85634 0
Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204
Country 85634 0
New Zealand
Phone 85634 0
+64274057415
Fax 85634 0
Email 85634 0
Matthew.Phillips@waikatodhb.health.nz
Contact person for public queries
Name 85635 0
Dr Matthew CL Phillips
Address 85635 0
Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204
Country 85635 0
New Zealand
Phone 85635 0
+64274057415
Fax 85635 0
Email 85635 0
Matthew.Phillips@waikatodhb.health.nz
Contact person for scientific queries
Name 85636 0
Dr Matthew CL Phillips
Address 85636 0
Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204
Country 85636 0
New Zealand
Phone 85636 0
+64274057415
Fax 85636 0
Email 85636 0
Matthew.Phillips@waikatodhb.health.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary