Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study.
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ABSTRACT:
SUBMITTER: van der Louw EJTM
PROVIDER: S-EPMC6589986 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PURPOSE:We conducted a feasibility study to investigate the use of ketogenic diets (KDs) as an adjuvant therapy for patients with glioblastoma (GBM), investigating (i) trial feasibility; (ii) potential impacts of the trial on patients' quality of life and health; (iii) patients' perspectives of their decision-making when invited to participate in the trial and (iv) recommending improvements to optimize future phase III trials. METHODS:A single-center, prospective, randomized, pilot study (KEATING), with an embedded qualitative design. Twelve newly diagnosed patients with GBM were randomized 1:1 to modified ketogenic diet (MKD) or medium chain triglyceride ketogenic diet (MCTKD). Primary outcome was retention at three months. Semi-structured interviews were conducted with a purposive sample of patients and caregivers (n = 15). Descriptive statistics were used for quantitative outcomes and qualitative data were analyzed thematically aided by NVivo. RESULTS:KEATING achieved recruitment targets, but the recruitment rate was low (28.6%). Retention was poor; only four of 12 patients completed the three-month diet (MCTKD n = 3; MKD n = 1). Participants' decisions were intuitive and emotional; caregivers supported diet implementation and influenced the patients' decision to participate. Those who declined made a deliberative and considered decision factoring diet burden and quality of life. A three-month diet was undesirable to patients who declined and withdrew. CONCLUSION:Recruitment to a KD trial for patients with GBM is possible. A six-week intervention period is proposed for a phase III trial. The role of caregivers should not be underestimated. Future trials should optimize and adequately support the decision-making of patients.
| S-EPMC7076054 | biostudies-literature
Project description:Concussion is the most common form of mild traumatic brain injury (mTBI). Although most patients' symptoms resolve within a month, patients with post-concussion syndrome (PCS) may continue to experience symptoms for years and have limited treatment options. This pilot study assessed the feasibility and symptom-related effects of a ketogenic diet (KD) in patients with PCS symptoms. The Ketogenic Diet in Post-Concussion Syndrome (KD-PCS) was a single-arm trial of a 2-month KD high in non-starchy vegetables and supplemented with medium-chain triglyceride (MCT) oil. Macronutrient targets were ≥70% fat, ≤10% carbohydrate, and the remainder as protein as energy. We assessed feasibility by daily self-reported measure of urine acetoacetate and collection of 3-day food records and serum beta-hydroxybutyrate at multiple timepoints. We assessed symptoms by administering the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and Modified Balance Error Scoring System (M-BESS) at baseline and month 2 and the Post-Concussion Symptom Scale (PCSS) at baseline, month 1, and month 2. Fourteen participants enrolled in the KD-PCS. Twelve participants completed the study and 11 implemented the KD (73% fat, 9% carbohydrate, and 18% protein) and achieved ketosis. One participant complained of MCT-related diarrhea that resolved and another reported nausea and fatigue that resulted in withdrawal from the study. Among compliant participants, the visual memory domain of the ImPACT improved by 12 points (p = 0.02) and PCSS scores improved by 9 points, although not statistically significant. This pilot trial suggests that the KD is a feasible experimental treatment for PCS and justifies further study of its efficacy.
| S-EPMC7511571 | biostudies-literature
Project description:BackgroundDiffuse intrinsic pontine glioma (DIPG) is one of the most devastating diseases among children with cancer, thus novel strategies are urgently needed.AimsWe retrospectively evaluated DIPG patients exposed to the carbohydrate restricted ketogenic diet (KD) with regard of feasibility, safety, and overall survival (OS).Methods and resultsSearches of MEDLINE and Embase identified five hits meeting the search criteria (diagnosis of DIPG and exposure to KD). One additional case was identified by contact with experts. Individual patient data were extracted from publications or obtained from investigators. The inclusion criteria for analysis of the data were defined as DIPG patients who were exposed to the KD for ≥3 months. Feasibility, as described in the literature, was the number of patients able to follow the KD for 3 months out of all DIPG patients identified. OS was estimated by the Kaplan-Meier method. Five DIPG patients (males, n = 3; median age 4.4 years; range, 2.5-15 years) meeting the inclusion criteria were identified. Analysis of the available data suggested that the KD is generally relatively well tolerated. Only mild gastro-intestinal complaints, one borderline hypoglycemia (2.4 mmol/L) and one hyperketosis (max 7.2 mmol/L) were observed. Five out of six DIPG patients identified adhered for ≥3 months (median KD duration, 6.5 months; range, 0.25-2 years) to the diet. The median OS was 18.7 months.ConclusionOur study provides evidence that it may be feasible for pediatric DIPG patients to adhere for at least 3 months to KD. In particular cases, diet modifications were done. The clinical outcome and OS appear not to be impacted in a negative way. KD might be proposed as adjuvant therapy when large prospective studies have shown feasibility and safety. Future studies might ideally assess the impact of KD on clinical outcome, quality of life, and efficacy.
| S-EPMC8551993 | biostudies-literature
Project description:Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.
| S-EPMC4063533 | biostudies-literature
Project description:BackgroundGlioblastoma multiforme (GBM) is an aggressive form of brain cancer which is associated with poor prognosis. A variety of oncolytic viruses have previously shown positive efficacy against GBM, potentially offering new treatment options for patients. One such oncolytic virus is Myxoma virus (MYXV), a rabbit-specific poxvirus that has been shown to be efficacious against a variety of tumor models including GBM.PurposeThe purpose of this study was to test the efficacy of MYXV combined with current treatment regimens for GBM in both established cell lines as well as patient biopsy samples.Materials and methodsU118 gliobastoma cell lines were treated under various standard of care combinations (untreated, radiation and chemotherapeutic) prior to infection with MYXV. Infection was then monitored for differences in rate of infection, titer and rate of spread. Cellular death was measured by MTT assay and Caspase-3 colorimetric assay. Patient biopsies were harvested and treated under similar treatment conditions.ResultsThe addition of GBM standard of care to MYXV infection resulted in an increased rate of spread compared to single treatment with either radiation or chemotherapeutic alone. SOC did not alter viral replication or infection rates. Similar effects were seen in ex vivo patient biopsies. Cellular viability was significantly decreased with the combination therapy of SOC and MYXV infection compared to any other treatment outcome. Caspase-3 activity was also significantly increased in samples treated with combination therapy when compared to any other treatment combination.ConclusionOur results show that the combination of MYXV with current SOC results in both increased killing of GBM cells compared to either treatment regime alone as well as increased spread of MYXV infection. These findings lay the foundation for future in vivo studies on combining MYXV with GBM SOC.
| S-EPMC6251439 | biostudies-literature
Project description:PURPOSE:Even with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12-15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma. Cx43-mediated gap junctional communication has been observed between tumor cells, between astrocytes and between tumor cells and astrocytes. Therefore, gap junction directed therapy using a pharmacological suppressor or modulator, such as tonabersat, could be a promising target in the treatment of GB. In this preclinical study, we evaluated the possible therapeutic potential of tonabersat in the F98 model. PROCEDURES:Female Fischer rats were inoculated with ± 25.000 F98 tumor cells in the right frontal lobe. Eight days post-inoculation contrast-enhanced T1-weighted (CE-T1w) magnetic resonance (MR) images were acquired to confirm tumor growth in the brain. After tumor confirmation, rats were randomized into a Control Group, a Connexin Modulation Group (CM), a Standard Medical Treatment Group (ST), and a Standard Medical Treatment with adjuvant Connexin Modulation Group (STCM). To evaluate therapy response, T2-weighted (T2w) and CE-T1w sequences were acquired at several time points. Tumor volume analysis was performed on CE-T1w images and statistical analysis was performed using a linear mixed model. RESULTS:Significant differences in estimated geometric mean tumor volumes were found between the ST Group and the Control Group and also between the STCM Group and the Control Group. In addition, significant differences in estimated geometric mean tumor volumes between the ST Group and the STCM Group were demonstrated. No significant differences in estimated geometric mean tumor volumes were found between the Control Group and the CM Group. CONCLUSION:Our results demonstrate a therapeutic potential of tonabersat for the treatment of GB when used in combination with radiotherapy and temozolomide chemotherapy.
| S-EPMC6802836 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) is the deadliest form of brain tumor with a more than 90% 5-year mortality. GBM has a paltry median survival of 12.6 months attributed to the unique treatment limitations such as the high average age of onset, tumor location, and poor current understandings of the tumor pathophysiology. The resection techniques, chemotherapic strategies, and radiation therapy currently used to treat GBM have slowly evolved, but the improvements have not translated to marked increases in patient survival. Here, we will discuss the recent progress in our understanding of GBM pathophysiology, and the diagnostic techniques and treatment options. The discussion will include biomarkers, tumor imaging, novel therapies such as monoclonal antibodies and small-molecule inhibitors, and the heterogeneity resulting from the GBM cancer stem cell population.
| S-EPMC4237465 | biostudies-literature
Project description:PurposePoor response to bariatric surgery, namely insufficient weight loss (IWL) or weight regain (WR), is a critical issue in the treatment of obesity. The purpose of our study was to assess the efficacy, feasibility, and tolerability of very low-calorie ketogenic diet (VLCKD) for the management of this condition.MethodsA real-life prospective study was conducted on twenty-two patients who experienced poor response after bariatric surgery and followed a structured VLCKD. Anthropometric parameters, body composition, muscular strength, biochemical analyses, and nutritional behavior questionnaires were evaluated.ResultsA significant weight loss (mean 14.1 ± 4.8%), mostly due to fat mass, was observed during VLCKD with the preservation of muscular strength. The weight loss obtained allowed patients with IWL to reach a body weight significantly lower than that obtained at the post-bariatric surgery nadir and to report the body weight of patients with WR at the nadir observed after surgery. The significantly beneficial changes in nutritional behaviors and metabolic profiles were observed without variations in kidney and liver function, vitamins, and iron status. The nutritional regimen was well tolerated, and no significant side effects were detected.ConclusionOur data demonstrate the efficacy, feasibility, and tolerability of VLCKD in patients with poor response after bariatric surgery.
| S-EPMC10371952 | biostudies-literature
Project description:Background:Glioblastoma is the commonest form of malignant brain tumour in adults, affecting 2-3 people per 100,000 per year. Despite current treatment options including surgical resection, radiotherapy and temozolomide chemotherapy, overall survival at 2 years is approximately 27%, with a median survival of 12-14 months. The ketogenic diet (KD) is postulated to work by simulating the metabolic response to fasting by promoting the utilisation of ketones as a primary energy source, and depriving the glycolytic pathways utilised by malignant glioma cells for growth. At present, there is no consensus as to which KD is preferable, with previous case series using different KDs, at different points in the treatment pathway. The aim of this randomised pilot study is to investigate protocol feasibility, tolerability and the impact on patient health and quality of life of two different KDs within an NHS setting. The results of this pilot study will inform which KD will be most deliverable and adhered to by patients in order to test for effectiveness in future trials. Methods:A prospective, non-blinded, randomised, pilot study will be undertaken in 12 patients with newly diagnosed glioblastoma treated by surgical resection. Patients will be randomised in a ratio of 1:1, using a permuted block randomisation method to one of two diets; the modified ketogenic diet and the medium chain triglyceride ketogenic diet. Primary data collection will take place 12 weeks after starting the diet and secondary data collection after 12 months. Feasibility will be assessed by retention and recruitment rates, ability to enrol patients prior to starting chemoradiotherapy, dietary compliance and adjustments, ketone levels, glucose levels and intervention time. Patient impact will be assessed through quality of life and food acceptability questionnaires, gastrointestinal side effects and changes to biochemical markers and anthropometric measures, assessed at regular intervals. Discussion:The results of this pilot study will be used to inform the feasibility, methodological design and power calculations of future phase III clinical trials investigating the effectiveness of KD as an adjuvant therapy in the management of glioblastoma. Trial registration:ISRCTN71665562 and NCT03075514.
| S-EPMC5704454 | biostudies-literature
Project description:The Ketogenic Diet (KD) is an effective, alternative treatment for refractory epilepsy. This high fat, low protein and carbohydrate diet mimics the metabolic and hormonal changes that are associated with fasting.To maximize the effectiveness of the KD, each meal is precisely planned, calculated, and weighed to within 0.1 gram for the average three-year duration of treatment. Managing the KD is time-consuming and may deter caretakers and patients from pursuing or continuing this treatment. Thus, we investigated methods of planning KD faster and making the process more portable through mobile applications.Nutritional data was gathered from the United States Department of Agriculture (USDA) Nutrient Database. User selected foods are converted into linear equations with n variables and three constraints: prescribed fat content, prescribed protein content, and prescribed carbohydrate content. Techniques are applied to derive the solutions to the underdetermined system depending on the number of foods chosen.The method was implemented on an iOS device and tested with varieties of foods and different number of foods selected. With each case, the application's constructed meal plan was within 95% precision of the KD requirements.In this study, we attempt to reduce the time needed to calculate a meal by automating the computation of the KD via a linear algebra model. We improve upon previous KD calculators by offering optimal suggestions and incorporating the USDA database. We believe this mobile application will help make the KD and other dietary treatment preparations less time consuming and more convenient.
| S-EPMC5546754 | biostudies-other