Brain TumorsNCT03328858
Ketogenic Diet in Children With Malignant or Recurrent/Refractory Brain Tumor
A study testing Ketogenic Diet in people with Brain Tumors, run by Nicklaus Children's Hospital f/k/a Miami Children's Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 12 months to 35 years
- Conditions the study is for
- Brain Tumors
- What is being tested?
- Ketogenic Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2017to 31 Jan 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of the Ketogenic Diet in Children With Malignant or Recurrent/Refractory Brain Tumor
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.
Read the detailed 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).
- Conditions
- Brain Tumors
- Being tested
- Ketogenic Diet
- Keywords
- Ketogenic Diet, brain tumors
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic DietOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Ketogenic Diet | Other | Participants will be provided a consultation with a ketogenic dietitian, and test the tolerance to the diet in an inpatient mode Receives: Other: Ketogenic Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
To evaluate the overall response rate of subjects with malignant or refractory brain tumors receiving dietary therapy with the ketogenic diet
Measured: one year
Secondary outcomes (4)
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).
Measured: one year
Ketosis Levels
To compare the betahydroxybutyrate level to decrease tumor size using MRI.
Measured: one year
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.
Measured: one year
Correlation of ketosis levels and ketogenic diet
To evaluate correlation between degree of ketosis (betahydroxybutyrate level) and ketogenic diet ratio.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2017
- Study start1 Nov 2017
- Primary completion31 Jan 2020
- Study completion31 Jan 2020
Why it stopped: PI no longer available, not able to find replacement. 2 patients, lost to follow-up.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Brain TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Ketogenic Diet will be initiated as inpatient, once all necessary studies are obtained and reviewed. The "classic ketogenic diet" will be initiated, and once ketosis is reached and patient demonstrates tolerance to diet he/she will be discharged home. Follow-up visits will be necessary up to 1 year.
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nicklaus Children's Hospital f/k/a Miami Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennifer Caceres, MS, RDN, Principal investigator, Nicklaus Children's HospitalZiad Khatib, MD, Study director, Nicklaus Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03328858
- Sponsor's protocol ID
- MCH05817
- Status last verified
- Jan 2020
- First submitted
- 23 Oct 2017
- Last updated
- 5 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gasior M, Rogawski MA, Hartman AL. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol. 2006 Sep;17(5-6):431-9. doi: 10.1097/00008877-200609000-00009.
PubMed 16940764Neal 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.
PubMed 19054400Kossoff EH. More fat and fewer seizures: dietary therapies for epilepsy. Lancet Neurol. 2004 Jul;3(7):415-20. doi: 10.1016/S1474-4422(04)00807-5.
PubMed 15207798Lussier 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.
PubMed 27178315Vidone 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.
PubMed 25668474Nebeling 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. doi: 10.1080/07315724.1995.10718495.
PubMed 7790697
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Ketogenic Diet in Children With Malignant or Recurrent/Refractory Brain Tumor
- ClinicalTrials.gov ID
- NCT03328858
- Acronym / sponsor ID
- MCH05817
- Conditions
- Brain Tumors
- Keywords
- Ketogenic Diet, brain tumors
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI no longer available, not able to find replacement. 2 patients, lost to follow-up.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Nicklaus Children's Hospital f/k/a Miami Children's HospitalUniversity, hospital or other
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Jan 2020 (actual)
- First posted
- 1 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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).
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Ketogenic Diet will be initiated as inpatient, once all necessary studies are obtained and reviewed. The "classic ketogenic diet" will be initiated, and once ketosis is reached and patient demonstrates tolerance to diet he/she will be discharged home. Follow-up visits will be necessary up to 1 year.
| Arm | Type | Receives |
|---|---|---|
| Ketogenic Diet | Other | Other: Ketogenic DietParticipants will be provided a consultation with a ketogenic dietitian, and test the tolerance to the diet in an inpatient mode |
Who may qualify
- Ages
- 12 months to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketogenic DietOnce 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. | Other | Ketogenic Diet |
Primary outcome
Overall Response Rate
Time frame: one year
To evaluate the overall response rate of subjects with malignant or refractory brain tumors receiving dietary therapy with the ketogenic diet
4 secondary outcomes
Quality of Life Measures
Time frame: one year
Ketosis Levels
Time frame: one year
Blood Glucose Levels
Time frame: one year
Correlation of ketosis levels and ketogenic diet
Time frame: one year
Results and safety
The study was stopped early (reason given: PI no longer available, not able to find replacement. 2 patients, lost to follow-up.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Background: PubMed 16940764Gasior M, Rogawski MA, Hartman AL. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol. 2006 Sep;17(5-6):431-9. doi: 10.1097/00008877-200609000-00009.
- Background: PubMed 19054400Neal 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.
- Background: PubMed 15207798Kossoff EH. More fat and fewer seizures: dietary therapies for epilepsy. Lancet Neurol. 2004 Jul;3(7):415-20. doi: 10.1016/S1474-4422(04)00807-5.
- Background: PubMed 27178315Lussier 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.
- Background: PubMed 25668474Vidone 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.
- Background: PubMed 7790697Nebeling 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. doi: 10.1080/07315724.1995.10718495.
- Nicklaus Children's HospitalLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Caceres, MS, RDN principal investigator
Nicklaus Children's Hospital
Ziad Khatib, MD study director
Nicklaus Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketogenic Diet in people with Brain Tumors, run by Nicklaus Children's Hospital f/k/a Miami Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: PI no longer available, not able to find replacement. 2 patients, lost to follow-up.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03328858, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.