Ketogenic Diet in Children With Malignant or Recurrent/Refractory Brain Tumor

Brain Tumors Clinical Trial

Official title:

A Phase II Study of the Ketogenic Diet in Children With Malignant or Recurrent/Refractory Brain Tumor

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03328858
• Other study ID #: MCH05817
• Status: Terminated
• Phase: N/A
• Start date: November 1, 2017
• Est. completion date: January 31, 2020

Study information

• Verified date: January 2020
• Source: Nicklaus Children's Hospital f/k/a Miami Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of the ketogenic diet on tumor size and quality of life in pediatric patients with malignant or recurrent/refractory brain tumors.

Description:

Brain tumors account for nearly 20% of all childhood malignancies. Of these, gliomas represent 50% of all brain tumors in children and young adults. Gliomas are classically divided into two subtypes - low-grade and high-grade. Low-grade gliomas (LGG) include pilocytic astrocytomas and diffuse astrocytomas, and high-grade gliomas (HGG) include anaplastic astrocytoma and glioblastoma multiforme. Although patients with grade I and II tumors have a good prognosis with 5-year overall survival rates of 80-90%, those cases that are recurrent, refractory, and/or unresectable remain a challenge. The prognosis of children and young adults with recurrent or refractory malignant brain tumors remains poor despite dramatic improvements in treatment over the past few decades, with only a minority achieving long-term survival if recurrence occurs following initial surgical resection and adjuvant chemotherapy.

For patients with HGG prognosis remains dismal despite aggressive treatment. In this subset of patients, the 5-year overall survival for anaplastic astrocytoma ranges from 20-40% and for glioblastoma 15-20%. Diffuse intrinsic brain stem gliomas (DIPG) have the worst overall prognosis with a nine-month mean overall survival and with most patients dying from the disease within 2 years. Thus, the development of new treatment protocols for children and young adults with both high grade gliomas and with recurrent or refractory low grade gliomas is crucial to improving the survival rates of these patients.

The Ketogenic Diet (KD) has been in clinical use for nearly a century, initially designed to mimic the effects of starvation. Over the last two decades metabolic studies have been gaining momentum as increasingly promising in disease modification of central nervous system disorders and tumors.

Tests in animals and studies in adult patients with brain tumors have shown that there are advantages to using the ketogenic diet. These include: improved response of the tumor to standard treatment (chemotherapy/radiation) and improvement in quality of life measures (alertness).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: January 31, 2020
• Est. primary completion date: January 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 35 Years

Eligibility

Inclusion Criteria:

• Diagnosis Medulloblastoma, high-grade glioma, low-grade glioma, and ependymoma are eligible. Other central nervous system tumors may be considered for treatment at discretion of investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic pathway tumor. The patient should have failed first line therapy and be considered refractory, relapsed, or recurrent. Exceptions are Grade III and Grade IV gliomas including brain stem gliomas who can be enrolled at initial diagnosis.

• Prior Therapy Patients should have already had first line standard of care therapy, unless their initial diagnosis is high grade glioma or DIPG in which case they are eligible. Patients with high grade glioma can be enrolled after the completion of initial radiation. Investigator discretion may also be used.

• Organ Function Requirements A. Functioning gastrointestinal system, i.e. ability to chew and swallow or alternative means of nutrition therapy such as a gastrostomy or jejunostomy tube B. SGPT (ALT) < 3 x upper normal limit; Total Bilirubin = 2 x upper normal limit C. No active pancreatitis D. No arrhythmia or prolonged QT.

Exclusion Criteria:

• History of cardiac arrhythmia

• Patient unable to chew/swallow and who do not consent to alternative methods of nutrition support, e.g. nasogastric or nasoduodenal tube, or gastrostomy or jejunostomy tube placement.

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumors

Intervention

Other:
• Ketogenic Diet
Once tolerance to the diet has been assessed, participants will be placed in the ketogenic diet, followed-up every three months until the one year completion.

Locations

Country	Name	City	State
United States	Nicklaus Children's Hospital	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (6)

Gasior M, Rogawski MA, Hartman AL. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol. 2006 Sep;17(5-6):431-9. Review. — View Citation

Kossoff EH. More fat and fewer seizures: dietary therapies for epilepsy. Lancet Neurol. 2004 Jul;3(7):415-20. Review. — View Citation

Lussier DM, Woolf EC, Johnson JL, Brooks KS, Blattman JN, Scheck AC. Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet. BMC Cancer. 2016 May 13;16:310. doi: 10.1186/s12885-016-2337-7. — View Citation

Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia. 2009 May;50(5):1109-17. doi: 10.1111/j.1528-1167.2008.01870.x. Epub 2008 Nov 19. — View Citation

Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr. 1995 Apr;14(2):202-8. — View Citation

Vidone M, Clima R, Santorsola M, Calabrese C, Girolimetti G, Kurelac I, Amato LB, Iommarini L, Trevisan E, Leone M, Soffietti R, Morra I, Faccani G, Attimonelli M, Porcelli AM, Gasparre G. A comprehensive characterization of mitochondrial DNA mutations in glioblastoma multiforme. Int J Biochem Cell Biol. 2015 Jun;63:46-54. doi: 10.1016/j.biocel.2015.01.027. Epub 2015 Feb 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	To evaluate the overall response rate of subjects with malignant or refractory brain tumors receiving dietary therapy with the ketogenic diet	one year
Secondary	Quality of Life Measures	To evaluate the changes of quality of life of subjects with relapsed or refractory brain tumors receiving dietary therapy with the ketogenic diet using age-appropriate quality of life modules (Peds QL).	one year
Secondary	Ketosis Levels	To compare the betahydroxybutyrate level to decrease tumor size using MRI.	one year
Secondary	Blood Glucose Levels	To compare average blood glucose during ketogenic diet initiation compared to decrease in tumor size at time of first follow-up MRI.	one year
Secondary	Correlation of ketosis levels and ketogenic diet	To evaluate correlation between degree of ketosis (betahydroxybutyrate level) and ketogenic diet ratio.	one year

External Links

•   Nicklaus Children's Hospital