Impact of a Ketogenic Diet Intervention During Radiotherapy on Body Composition

Study Overview
=================
Brief Summary
-----------------
Type of study: Pilot / phase I trial Study purpose To assess the impact of a dietary intervention during radio(chemo)therapy (RCT) on body composition changes Trial Treatment Patients will be split into a control group and intervention group 1. If willing to undertake a ketogenic diet for the duration of radiotherapy, patients are entered into intervention group 2. Group 1: On irradiation days irradiation after overnight fast + ketogenic breakfast consisting of 50-250 ml betaquik® (vitaflo, Bad Homburg, Germany) and 10g MyAmino (dr. reinwald healthcare gmbh + co kg, Altdorf, Germany). Group 2: Complete ketogenic diet plus 10g MyAmino/day Control: No dietary intervention. All groups: Weight measurements and bioimpedance analysis (BIA) once per week, routine blood parameters and quality of life (QoL) questionnaire before, during and after RCT Endpoints Primary: Feasibility of the dietary intervention during RCT, measured by dropout rates Changes in body weight BIA phase angle and quantities derived from BIA variables Secondary: QoL Toxicities Blood parameters Grade of regression at time of surgery in case of rectum carcinomas Inclusion criteria One of the following tumor entities: Breast carcinoma Rectum carcinoma Head & Neck Cancer Histological confirmation of malignancy Signed written informed consent Karnofsky index ≥ 70 Age between 18 and 75 years BMI between 18 and 34 kg/m^2 Exclusion criteria Palliative patients, in particular with metastasis Type I diabetes Pregnancy Pacemaker and other metallic parts within the body Known defects in enzymes necessary for ketogenesis, ketolysis, fatty acid oxidation or gluconeogenesis Unable to speak or understand German Cognitive impairments or psychological disorders Renal insufficiency Planned accrual 15 patients with colorectal and mammary tumor plus 5 patients with H&N cancer in intervention group 1 15 patients with colorectal and mammary tumor plus 5 patients with H&N cancer in control group Minimum 5 patients of each tumor entity in intervantion group 2 Total: n ≥ 85 patients Study procedure Inclusion and full written informed consent. Baseline BIA measurement and blood work RCT with weekly BIA assessments; at least one blood withdrawal ± concurrent dietary intervention Final BIA measurement and blood work after radiotherapy Follow up For rectal carcinoma: Regression at time of surgery (c and p)

Official Title
-----------------
Investigating the Impact of a Ketogenic Diet Intervention During Radiotherapy on Body Composition: A Pilot Trial

Conditions
-----------------
Neoplasms

Intervention / Treatment
-----------------
* Dietary Supplement: MyAmino
* Dietary Supplement: betaquik
* Radiation: Radio(chemo)therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: RT of one of the following tumor entities: Mammary carcinoma, colorectal carcinoma, head and neck carcinoma Histologicallý confirmed malignant Tumor Written informed consent Karnofsky index >= 70 18 kg/m^2 < BMI < 34 kg/m^2 Exclusion Criteria: Palliative Treatment Type I Diabetes Pregnancy Pacemaker and othe rmetallic parts that make BIA predictions unreliable Unable to understand and speak German Cognitive impairments Renal insufficiency intake of carboanhydrase-inhibitors Rare metabolic disorders that speak against a ketogenic diet

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Control group that will not receive advice to follow a ketogenic diet or reduce carbohydrates. | Radiation: Radio(chemo)therapy<br>* Radio(chemo)therapy as recommended by the institutional interdisciplinary tumor board.<br>|
| Experimental: Intervention group 1<br>Patients who will receive each radiotherapy (RT) fraction after an overnight fast and subsequently ingest a ketogenic breakfast consisting of (i) up to 250 ml of a medium chain triglyceride drink (betaquik, vitaflo) plus (ii) 10g amino acids (MyAmino, dr. reinwald gmbh + co kg). | Dietary Supplement: MyAmino<br>* MyAmino is a supplement containing the eight essential amino acids. MyAmino has a theoretical net nitrogen utilization of 99%, so that almost no glucose will be created out of the maino acids.<br>* Other names: Master amino acid pattern (MAP);Dietary Supplement: betaquik<br>* betaquik is a medium chain triglyceride (MCT) emulsion. One bottle is 225ml corresponding to 45g MCT fats.<br>Radiation: Radio(chemo)therapy<br>* Radio(chemo)therapy as recommended by the institutional interdisciplinary tumor board.<br>|
| Experimental: Intervention group 2<br>Patients who will follow a ketogenic diet throughout the whole period of RT, Patients don't have to fast prior to each RT fraction, but will receive MyAmino analogous to Intervention group 1. | Dietary Supplement: MyAmino<br>* MyAmino is a supplement containing the eight essential amino acids. MyAmino has a theoretical net nitrogen utilization of 99%, so that almost no glucose will be created out of the maino acids.<br>* Other names: Master amino acid pattern (MAP);Radiation: Radio(chemo)therapy<br>* Radio(chemo)therapy as recommended by the institutional interdisciplinary tumor board.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dropout rate | Dropout rates (intervention groups 1+2) to assess feasibility/tolerability of the intervention | 5-6 weeks | 
| Body composition | This is a composite measure of several parameters obtained from the bioimpedance scale (mBCA 515, seca Germany). Body weight and composition derived from bioimpedance analysis will be assessed at least once per week. Body composition is composed of fat mass, fat free mass, total body water, extracellular water and intracellular water. | 5-6 weeks | 
| Phase angle | The phase angle is a raw parameter of bioimpedance analysis and will be tracked weekly at a total of 19 frequencies (1, 1.5,2,3,5,7.5,10,15,20,30,50,75,100,150,200,300,500,1000 kHz). The Focus will be on the Phase angle at 50kHz which is a standard frequency of most BIA devices. | 5-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life | Evaluation of quality of life using EORTC QLQ-C30 and site-specific questionnaires at start, in the middle and at the end of RT. | 5-6 weeks | 
| Blood parameters | This is a composite measure of relevant blood parameters including small blood count, glucose, albumin, urea, HbA1c, beta-hydroxybutyrate, triglycerides, HDl and LDL cholesterol, creatinine, liver enzymes, insulin, IGF-1, TSH, free T3 and T4. | Blood parameters will be determined up to one week before the first RT fraction, at least once during their RT course (after an expected 3 weeks) and during their last week of RT.. | 
| Regression grade (TNM classification) | Only for colorectal carcinoma patients undergoing neoadjuvant RT: cTN status prior to and ypTN status after surgery | 12 weeks | 
| Normal tissue toxicity after RT | Toxicity related to RT evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. | 5-6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ketogenic Diet, Body composition, Radiation therapy