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Trial registered on ANZCTR


Registration number
ACTRN12620001310954
Ethics application status
Not required
Date submitted
23/07/2020
Date registered
4/12/2020
Date last updated
4/12/2020
Date data sharing statement initially provided
4/12/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Managing Glioblastoma Multiforme with Fasting and a Ketogenic Diet
Scientific title
Managing Glioblastoma Multiforme with Fasting and a Ketogenic Diet: A Case Series
Secondary ID [1] 301868 0
None.
Universal Trial Number (UTN)
U1111-1256-0073
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 318363 0
Condition category
Condition code
Cancer 316381 316381 0 0
Brain

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a prospective observational study. Patients diagnosed with stage 4 glioblastoma will be informed of the potential benefits and risks of using fasting and a ketogenic diet in glioblastoma. If the patient opts to incorporate this approach into their lifestyle, they will be supported with information and guidance prior to commencing the regimen via a clinical visit at Waikato hospital, followed by video (Zoom) sessions every 1-2 weeks thereafter. The recommended regimen will consist of 5-7 days of fasting, alternated with 3 weeks of a ketogenic diet, for a period of up to 2 years post-diagnosis (or more if the patient remains alive, well, and wishes to continue). Observational data (such as MRI scans) will be collected as per the patient's routine care by their treating oncologist, who will be informed of the fasting and ketogenic diet regimen. There will be no further study visits at the hospital other than routine oncology care, unless the situation warrants (such as an unexpected admission for a medical complication of any description).

(1) Materials.
- Fasting materials will include a CareSens blood glucose and ketone monitor (patients will buy).
- Ketogenic diet materials include a diet plan with recipes (on average, per 1,750 kcal per day, the recipes will be composed of 152 g of fat (67 g saturated), 75 g of protein, 16 g net carbohydrate, and 11 g of fiber). This plan is designed by the lead investigator. Patients will also be able to source their own ketogenic diet recipes, although these will be checked by the lead investigator to ensure the fat/carbohydrate/protein ratio conforms to the ratio above.

(2) Procedures.
- Fasting procedure will be a fluid-only fast (water, salt supplementation, black coffee, tea, or bone broth) for 5-7 days in a row. Lemon and lime juice, apple cider vinegar, 1 tsp chia or flax seeds, or a slice of fruit (not to be eaten) may be added to each glass of water. Up to 1 tsp of unsweetened almond milk, cream, coconut oil, butter, MCT oil, or a pinch of cinnamon or nutmeg may be added to coffee, which will be limited to 2-4 cups per day. There will be regular email contact (every 1-2 days) and video sessions on Zoom (at least one per fast, anticipated to be 30-60 minutes long) to maintain contact with patients and help them surmount any difficulties.
- Ketogenic diet will be as per the diet plan, no limit on the amount of food that may be eaten (ad libitum).
- It is anticipated there will be approximately one fast per month, with all remaining time spent on the ketogenic diet.

(3) Delivery.
- The patient (and partner, if present) will deliver the fasting and ketogenic diet interventions to themselves. The study investigators will only provide guidance and aid in troubleshooting via video (Zoom) throughout. The conversations will be part educational, part question and answer sessions, part support (as any routine clinic visit would be, albeit via video) so as to maximize the chances of success with the diet and fasts. It is anticipated that the sessions will be anywhere from 20-60 minutes in duration. Patients will also be contacted regularly via email to provide encouragement and review any potential problems, email frequency will vary depending on patient need however anticipated to be 1-2 emails a week during the ketogenic diet phase, 3-4 emails a week during the fasts.

(4) Location.
- Fasting and ketogenic diet therapy will largely take place in the patient's own home.

(5) Adherence.
- This will be assessed by monitoring of blood ketone (beta-hydroxybutyrate) levels, daily during the fasts (aiming for average of 2 mmol/L or higher) and 1-3 times per week for the ketogenic diet (aiming for average of 0.6 mmol/L or higher).
Intervention code [1] 318160 0
Not applicable
Comparator / control treatment
No control group, prospective observational case series only.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 324534 0
Overall survival.
Timepoint [1] 324534 0
2 years from the time of glioblastoma diagnosis (histologically confirmed on brain biopsy).
Secondary outcome [1] 384929 0
Patient functional status, with Eastern Cooperative Oncology Group (ECOG) performance status scale (completed by lead investigator in a clinic room).
Timepoint [1] 384929 0
2 years from glioblastoma diagnosis.
Secondary outcome [2] 384930 0
Patient quality of life, with functional assessment of cancer therapy - brain (Fact-Br) (completed by patient in a clinic room).
Timepoint [2] 384930 0
2 years from glioblastoma diagnosis.
Secondary outcome [3] 384931 0
Weight (kg, measured by lead investigator on a balance scale in clinic room).
Timepoint [3] 384931 0
2 years from glioblastoma diagnosis.
Secondary outcome [4] 384932 0
MRI tumour features, including volume (cubic cm, assessed by a hospital neuroradiologist blinded to treatment).
Timepoint [4] 384932 0
2 years from glioblastoma diagnosis.
Secondary outcome [5] 388239 0
Blood glucose level (mmol/L) via serum assay.
Timepoint [5] 388239 0
3 days per week (bedtime) throughout the 2-year study.
Secondary outcome [6] 388240 0
Blood beta-hydroxybutyrate (ketone) level (mmol/L) via serum assay.
Timepoint [6] 388240 0
3 days per week (bedtime) throughout the 2-year study.

Eligibility
Key inclusion criteria
(1) Age 18 years or greater.
(2) Histologically confirmed diagnosis of glioblastoma on brain biopsy.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) A medical or psychiatric disorder that would make it difficult to complete the fasting periods or the ketogenic diet.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Both
Statistical methods / analysis
Only descriptive statistics such as means, medians, standard deviations, and standard errors) will be provided. Kaplan-Meir curves may be presented.

Recruitment
Recruitment status
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] 22790 0
New Zealand
State/province [1] 22790 0
Anywhere in New Zealand

Funding & Sponsors
Funding source category [1] 306290 0
Self funded/Unfunded
Name [1] 306290 0
NA
Address [1] 306290 0
NA
Country [1] 306290 0
Primary sponsor type
Individual
Name
Matthew Phillips
Address
Neurology Dept, Level 1 Reception A, Waikato Hospital, Pembroke St, Hamilton Waikato NZ 3024
Country
New Zealand
Secondary sponsor category [1] 307060 0
None
Name [1] 307060 0
Address [1] 307060 0
Country [1] 307060 0

Ethics approval
Ethics application status
Not required

Summary
Brief summary
The purpose of this study is to examine the impact of a combined fasting and ketogenic diet protocol on the overall survival of patients with glioblastoma.

Who is it for?
You may be eligible for this study if you are an adult aged 18 or older, have a confirmed diagnosis of glioblastoma (based on brain biopsy), and do not have another medical condition that would make it difficult to complete the fasts and ketogenic diet.

Study details
Participants in this study will be provided instructions on how to follow a combined fasting and ketogenic diet plan, including recipes for ketogenic meals. Participants will undergo a monthly fasting period of 5-7 days during which they will not eat any solid foods, but will be able to consume water, salt tablets, black coffee or tea every day for the 5-7 days. During the fast period, participants will have regular email and video conference sessions with the study team to monitor their progress and have any questions answered. Participants will need to purchase a CareSens blood glucose and ketone monitor and will test their blood via a finger prick daily during the fasts to monitor their blood glucose and ketone levels. Between the fasts, participants will follow a ketogenic diet plan where they can eat as much as they want each day for 3 weeks. During the ketogenic diet period, participants will continue to monitor their blood glucose and ketone levels and adjust their daily diet as needed to meet the target blood ketone levels. The two fasting and ketogenic diet periods will be cycled continuously for up to 2 years (or longer), and participants will be asked to complete a study visits 2 years post-biopsy diagnosis of glioblastoma. During the study visits, participants will have their weight recorded, and will also complete a quality of life questionnaire, as well as a functional assessment to determine their current abilities. Participants will also undergo an MRI scan to determine their tumour size at approximately 3-4 month intervals (this will be incorporated as part of their routine tumour surveillance by the treating oncologist).

It is hoped this research will provide information regarding whether the combination of fasting and a ketogenic diet has any influence on tumour growth and survival in patients with glioblastoma.
Trial website
Trial related presentations / publications
Public notes
This study initially commenced as a case report, which the Waikato District Health Board Office prospectively advised did not require ethics review so long as informed consent was obtained. However, when additional patients with glioblastoma multiforme voiced a desire to undergo a fasting and ketogenic diet strategy, this study turned into a prospective observational case series.

Thus, a Scope of Review form was submitted to the Health and Disability Ethics Committee of New Zealand, which formally waived the requirement for ethics review on October 27, 2020, given that this is a prospective observational case series with no change to standard treatment other than information and advice on how to incorporate periodic fasting and a ketogenic diet into their lifestyle, that all patients are providing informed consent, that the investigators will not collect or store any human tissue, and that all information collected will be presented in a de-identified format in any presentation or publication.

Contacts
Principal investigator
Name 104098 0
Dr Matthew CL Phillips
Address 104098 0
Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204
Country 104098 0
New Zealand
Phone 104098 0
+64274057415
Fax 104098 0
Email 104098 0
Matthew.Phillips@waikatodhb.health.nz
Contact person for public queries
Name 104099 0
Dr Matthew CL Phillips
Address 104099 0
Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204
Country 104099 0
New Zealand
Phone 104099 0
+64274057415
Fax 104099 0
Email 104099 0
Matthew.Phillips@waikatodhb.health.nz
Contact person for scientific queries
Name 104100 0
Dr Matthew CL Phillips
Address 104100 0
Neurology Dept, Waikato Hospital, Pembroke St, Hamilton NZ 3204
Country 104100 0
New Zealand
Phone 104100 0
+64274057415
Fax 104100 0
Email 104100 0
Matthew.Phillips@waikatodhb.health.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Potentially any data requested, depends on intended use (but will all be de-identified).
When will data be available (start and end dates)?
Immediately upon (same day of) publication, no end date.
Available to whom?
Medical professionals and researchers.
Available for what types of analyses?
Any statistical analysis.
How or where can data be obtained?
Emailing the corresponding author at Matthew.Phillips@waikatodhb.health.nz.
What supporting documents are/will be available?
No other documents available
Summary results
No Results