Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000027314
Ethics application status
Approved
Date submitted
19/12/2016
Date registered
9/01/2017
Date last updated
16/07/2021
Date data sharing statement initially provided
16/07/2021
Date results information initially provided
16/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing The Effects Of A Low Fat Diet Versus A Ketogenic Diet On The Motor And Non-Motor Symptoms Of Parkinson's Disease: A Randomized Controlled Trial
Scientific title
Comparing The Effects Of A Low Fat Diet Versus A Ketogenic Diet On The Motor And Non-Motor Symptoms Of Parkinson's Disease: A Randomized Controlled Trial
Secondary ID [1] 290703 0
None
Universal Trial Number (UTN)
U1111-1185-9688
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's Disease 301257 0
Condition category
Condition code
Neurological 301016 301016 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a randomized controlled study with 10-40 patients in each of two groups (20-80 patients total). The study will last for ten weeks, although the actual dietary intervention will only be for eight weeks.

(1) Diets.

Patients will be given a four-week meal plan containing information about their diet, grocery shopping lists for each week, standard meal plan recipes, optional calorie booster recipes, and a cheat diary.

Two different diets will be compared. The first diet will be low fat (1758 calories, 42 g fat, 75 g protein, 246 g net carbohydrate per day); by weight, the percentages will be 11% fat versus 62% net carbohydrate. The second diet will be high fat ketogenic (1758 calories, 152 g fat, 75 g protein, 16 g net carbohydrate per day - in other words, a 1.5:1 modified ketogenic diet); by weight, the percentages will be 60% fat versus 6% net carbohydrate. Notably, calorie and protein intake per day will be the same in both diets.

The 1758 calories per day and macronutrient ratios given above will be the baseline diet that all participants will be expected to be able to consume. However, some participants will clearly require a higher caloric intake than this. We will provide simple recipes that substantially increase caloric intake but minimally affect protein intake for each group. For the low fat diet several low fat, high net carbohydrate supplemental options (such as fruit shakes) will be provided to the participants. For the ketogenic diet several high fat, low net carbohydrate supplemental options (such as fat shakes) will be provided to the participants. These options will allow for more calories to be consumed while maintaining the relevant fat to net carbohydrate ratio, without significantly increasing protein consumption.

We will not ask the patient to maintain a detailed food diary as proof of their sticking to the diet, as previous studies have shown these to be burdensome from the patient perspective. However, we will prescribe a “cheat” diary to each patient such that if they do deviate from the meal plan, they write down the details of the food they ate that was not part of the meal plan.

Dietary education and counselling will be provided throughout the study to assist patients with the practical aspects of their diet. We will endeavour to represent both diets as potentially providing health benefits.


(2) Assessments.

There will be one screening visit one month before the study starts for the following:

(1) 0-60 minutes - Lead investigator presentation including explanation of Participant Information Sheet and signing of Consent Form.
(2) 60-90 minutes - Parkinson’s nurse assessment on demographics, home situation, comorbidities, Parkinson’s diagnosis, Montreal Cognitive Assessment (MoCA) score, constipation including Bowel Function Index (BFI) score, and medications/medication allergies.
(3) 90-150 minutes - Nutrition specialist assessment regarding meal preparation abilities, food preferences/food allergies, and physical status.

Information required to calculate body mass index and recommended daily calorie intake will be gathered at the screening visit, but these variables will be calculated after the visit.

There will be four clinical visits at Weeks 1, 2, 6, and 10 for the following:

(1) 0-15 minutes - Document weight and body mass index, lying and standing blood pressure, and explain and record glucose/ketone monitor.
(2) 15-30 minutes - Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) questionnaire.
(3) 30-60 minutes - MDS-UPDRS blinded neurologist assessment (non-motor aspects of daily living, motor aspects of daily living, motor examination, motor complications).
(4) 60-75 minutes - Bloods (CBC, EUC, lipids, uric acid, CRP).


(3) Procedure.

Months Before
Ads in local and nation-wide Parkinson’s newsletters.
Presentations to enhance awareness of study.

Month Before
Screening visit.

Week 1
First clinical visit.
Hand out and explain how to use glucose/ketone monitor.
Week 2
Second clinical visit.
Randomize and hand out meal plans, including cheat diaries.

Week 3
Participants commence individual meal plans.
Week 4
Continue.
Week 5
Continue.
Week 6
Third clinical visit.
Immediately after the visits are completed, MDS-UPDRS scores will be analyzed to see if one meal plan is superior (participants on one meal plan have significantly improved scores compared to their aggregate baseline scores, or participants on the other meal plan have significantly worse scores compared to their aggregate baseline scores).
- If one meal plan is superior, all participants go on the superior meal plan.
- Otherwise, all participants stay on their current meal plan.

Week 7
Participants commence superior meal plan, or stay on current meal plan.
Week 8
Continue.
Week 9
Continue.
Week 10
Fourth clinical visit.

Month After
Results relayed to group.

*Patients will have 24-hour access to a neurologist and a Parkinson’s nurse throughout the study.
*Patients will also be contacted by phone or email every week to see how they are going.
Intervention code [1] 296590 0
Lifestyle
Intervention code [2] 296757 0
Treatment: Other
Comparator / control treatment
The control group will be low fat (1758 calories, 42 g fat, 75 g protein, 246 g net carbohydrate per day); by weight, the percentages will be 11% fat and 62% net carbohydrate. Carbohydrates will be primarily derived from vegetables, fruits, and multigrain breads.
Control group
Active

Outcomes
Primary outcome [1] 300512 0
Severity of Parkinson's Disease motor and non-motor symptoms using the MDS-UPDRS score. This will be undertaken by a neurologist, blinded to the meal plan that the patient is currently taking.
Timepoint [1] 300512 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).
Secondary outcome [1] 330169 0
Body mass index assessed by BMI calculator
Timepoint [1] 330169 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).
Secondary outcome [2] 330452 0
Lying and standing blood pressure assessed with electronic blood pressure monitor
Timepoint [2] 330452 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).
Secondary outcome [3] 330455 0
Lipid profile assessed by serum assay
Timepoint [3] 330455 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).
Secondary outcome [4] 330456 0
Uric acid assessed by serum assay
Timepoint [4] 330456 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).
Secondary outcome [5] 330457 0
C-reactive protein assessed by serum assay
Timepoint [5] 330457 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).
Secondary outcome [6] 330528 0
Blood glucose assessed by Freestyle Precision NeoMonitor
Timepoint [6] 330528 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).
Secondary outcome [7] 330529 0
Blood ketones assessed by Freestyle Precision NeoMonitor
Timepoint [7] 330529 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).
Secondary outcome [8] 335221 0
Glycosylated hemoglobin assessed by serum assay.
Timepoint [8] 335221 0
Baseline assessments Weeks 1 and 2. Assessment end of Week 6 (four weeks post commencing meal plan). Assessment end of Week 10 (four weeks post commencing superior or current meal plan).

Eligibility
Key inclusion criteria
Age 40-75 years.
Body mass index >18.5.
Montreal cognitive assessment (MoCA) >20.
Parkinson’s diagnosis fulfilling UK Brain Bank criteria.
Sufficient motivation and ability to follow either meal plan.
Minimum age
40 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to provide informed consent or speak and understand English.
A substance abuse, mental health, or medical condition that in the opinion of the investigators would make it difficult for the patient to take part in the study.
Parkinson’s Disease extremely mild or extremely severe (Hoehn and Yahr Stages 0 and 5).
Current use of weight-loss medications.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/05/2017
Actual
29/04/2017
Date of last participant enrolment
Anticipated
30/06/2017
Actual
7/06/2017
Date of last data collection
Anticipated
18/08/2017
Actual
18/08/2017
Sample size
Target
40
Accrual to date
Final
47
Recruitment outside Australia
Country [1] 8514 0
New Zealand
State/province [1] 8514 0
Waikato

Funding & Sponsors
Funding source category [1] 295199 0
Hospital
Name [1] 295199 0
Waikato Hospital Neurology Department
Country [1] 295199 0
New Zealand
Primary sponsor type
Hospital
Name
Waikato Hospital
Address
Selwyn and Pembroke Street, Hamilton 3204
Country
New Zealand
Secondary sponsor category [1] 294031 0
None
Name [1] 294031 0
Address [1] 294031 0
Country [1] 294031 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296549 0
Health and Disability Ethics Committee
Ethics committee address [1] 296549 0
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 296549 0
New Zealand
Date submitted for ethics approval [1] 296549 0
08/08/2016
Approval date [1] 296549 0
14/09/2016
Ethics approval number [1] 296549 0
16/STH/133

Summary
Brief summary
Parkinson’s disease may result from mitochondrial dysfunction and chronic cell energy failure (1,2). If so, a high fat, low carbohydrate “ketogenic” diet may alleviate this chronic energy failure as ketones compensate for deteriorating brain glucose metabolism (3,4), bypass deficient Complex I activity (5,6), and provide more ATP per unit oxygen than glucose (7). Previous studies have shown that physiological ketosis is beneficial in epilepsy (8) and Alzheimer’s disease (9,10). To date, one study has examined the ketogenic diet in Parkinson’s (11); it lacked a control arm.

Objectives:
In mid-2017, the Waikato Hospital neurology department will run a randomized controlled study with two objectives - first, to show it is feasible to institute a ketogenic diet in patients with Parkinson’s, second, to compare the effects of a low fat diet versus a ketogenic diet on motor and non-motor symptoms of Parkinson’s.

Methods:
Randomized controlled study over ten weeks. Baseline assessments in week 1 and 2. In week 3, participants randomized to either low fat or ketogenic diet followed by blinded clinical assessment at end of week 6. In week 7, all participants go on superior or current diet followed by blinded clinical assessment at end of week 10.

(1) Bose and Beal. 2016. Mitochondrial dysfunction in Parkinson’s disease. Journal of Neurochemistry 139(Suppl 1), 216-231.
(2) Perier and Vila. 2012. Mitochondrial biology and Parkinson’s Disease. Cold Spring Harbor Perspectives in Medicine 4:a009332, 1-19.
(3) Roy et al. 2012. The ketogenic diet increases brain glucose and ketone uptake in aged rats: a dual tracer PET and volumetric MRI study. Brain Research 1-10.
(4) Cunnane et al. 2011. Brain fuel metabolism, aging, and Alzheimer’s disease. Nutrition 27(1), 1-41.
(5) Tieu et al. 2003. D-ß-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. The Journal of Clinical Investigation 112(6), 892-901.
(6) Gasior et al. 2006. Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioural Pharmacology 17(5-6), 431-439.
(7) Veech. 2004. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins, Leukotrienes, and Essential Fatty Acids 70(3), 309-319.
(8) Neal et al. 2008. The ketogenic diet for the treatment of childhood epilepsy: a randomized controlled trial. Lancet Neurology 7(6), 700-706.
(9) Reger et al. 2004. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiology of Aging 25, 311-314.
(10) Henderson et al. 2009. Study of theketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutrition and Metabolism 6(31), 1-25.
(11) VanItallie et al. 2005. Treatment of Parkinson disease with diet-induced hyperketonemia; A feasibility study. Neurology 64, 728-730.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71006 0
Dr Matthew CL Phillips
Address 71006 0
Neurology Department, Waikato Hospital
Selwyn and Pembroke Street
Hamilton 3204
Country 71006 0
New Zealand
Phone 71006 0
+64274057415
Fax 71006 0
Email 71006 0
[email protected]
Contact person for public queries
Name 71007 0
Dr Matthew CL Phillips
Address 71007 0
Neurology Department, Waikato Hospital
Selwyn and Pembroke Street
Hamilton 3204
Country 71007 0
New Zealand
Phone 71007 0
+64274057415
Fax 71007 0
Email 71007 0
[email protected]
Contact person for scientific queries
Name 71008 0
Dr Matthew CL Phillips
Address 71008 0
Neurology Department, Waikato Hospital
Selwyn and Pembroke Street
Hamilton 3204
Country 71008 0
New Zealand
Phone 71008 0
+64274057415
Fax 71008 0
Email 71008 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely ... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLow-fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial.2018https://dx.doi.org/10.1002/mds.27390
EmbaseKetogenic Diet: An Effective Treatment Approach for Neurodegenerative Diseases.2022https://dx.doi.org/10.2174/1570159X20666220830102628
N.B. These documents automatically identified may not have been verified by the study sponsor.