ANZCTR - Registration

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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

21/10/2022

Date data sharing statement initially provided

4/12/2020

Date results information initially provided

22/12/2021

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]

None.

Universal Trial Number (UTN)

U1111-1256-0073

Trial acronym

Linked study record

Health condition

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

Glioblastoma

Condition category

Condition code

Cancer

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 weekly emails and, if requested by the patient, video (Zoom) sessions as needed. 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 weekly email contact and occasional video sessions (one on the initial fast, more as required later, anticipated to be 20-60 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 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 (anticipated to be 1-2 emails a week during the ketogenic diet phase and 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 glucose and ketone (beta-hydroxybutyrate) levels, daily during the fasts and three times per week for the ketogenic diet (aiming for a mean glucose to ketone ratio of < 6).

Intervention code [1]

Not applicable

Comparator / control treatment

No control group, prospective observational case series only.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Feasibility as determined by glucose to ketone ratio, calculated by dividing the blood glucose level (mmol/L via serum assay) by the beta-hydroxybutyrate (ketone) level (mmol/L via serum assay) to achieve a proportionate value.

Timepoint [1]

From day of commencing fasting and ketogenic diet strategy, daily during the fasts and 3 days per week during the ketogenic diet to the date of cessation of either strategy, up to 2 years post-commencement.

Secondary outcome [1]

Patient functional status, with Eastern Cooperative Oncology Group (ECOG) performance status scale (completed by lead investigator in a clinic room).

Timepoint [1]

On the day of commencing the fasting and ketogenic diet strategy and on the date of cessation of either the fasting or ketogenic diet strategy, up to 2 years post-commencement.

Secondary outcome [2]

Weight (kg, measured by lead investigator on a balance scale in clinic room).

Timepoint [2]

Weight will be measured twice. Once on the day of commencing the fasting and ketogenic diet strategy, and once again on the date of cessation of the fasting or ketogenic diet strategy, up to 2 years post-commencement..

Secondary outcome [3]

MRI tumour features, including volume (cubic cm, assessed by a hospital neuroradiologist blinded to treatment).

Timepoint [3]

MRI tumour features will be assessed twice. Once for the most recent MRI done prior to commencement of the fasting and ketogenic diet strategy, and once again on the most recent MRI done prior to cessation of the fasting and ketogenic diet strategy, up to 2 years post-commencement.

Secondary outcome [4]

Blood glucose level (mmol/L) via serum assay.

Timepoint [4]

Secondary outcome [5]

Blood beta-hydroxybutyrate (ketone) level (mmol/L) via serum assay.

Timepoint [5]

Secondary outcome [6]

Safety as measured by a study-specific questionnaire.

Timepoint [6]

Safety will be assessed once, on the day of cessation of either the fasting or ketogenic diet strategy, up to 2 years post-commencement.

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

Sex

Both males and females

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

Actual

8/03/2020

Date of last participant enrolment

Anticipated

23/06/2021

Actual

5/12/2020

Date of last data collection

Anticipated

23/06/2023

Actual

7/06/2021

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Anywhere in New Zealand

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Not required

Summary

Brief summary

The purpose of this study is to examine whether a combined fasting and ketogenic diet strategy is feasible, safe, and capable of sustaining a potentially therapeutic level of ketosis (defined as a glucose to ketone ratio <6) in patients with glioblastoma multiforme.

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 email and video conference sessions as needed 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 as long as the participant wishes, up to 2 years post-commencement. 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 is feasible in patients with glioblastoma multiforme.

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

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

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 scientific queries

Name

Dr 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)?

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 [email protected].

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Phillips MCL, Leyden J, McManus EJ, et al. Feasibi... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series.	2022	https://dx.doi.org/10.1155/2022/4496734

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically