Feasibility of a Carbohydrate-restricted, High-fat Diet on Head and Neck Squamous Cell Carcinoma Outcomes

Study Overview
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Brief Summary
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This study will test the feasibility of a carbohydrate-restricted, high-fat (CRHF) diet intervention in newly diagnosed head and neck squamous cell carcinoma patients who will receive definitive radiation.

Detailed Description
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Our previous observational research indicates that a pretreatment diet high in total carbohydrates is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer. The purpose of this study is to conduct a single-blinded randomized controlled trial to test the feasibility of a carbohydrate-restricted, high-fat (CRHF) diet intervention in newly diagnosed head and neck cell squamous carcinoma (HNSCC) patients who will receive definitive radiation. The secondary aim is to collect preliminary data on the effect of the intervention on tumor progression, nutritional status, body composition, quality of life, and symptom burden. Thirteen newly diagnosed HNSCC non-metastatic patients were recruited from Augusta Victoria Hospital in East Jerusalem and randomized into one of two arms; a carbohydrate-restricted, high-fat diet arm (arm A) and a regular diet composition arm (Arm B). Arm A (N=6) were provided a CRHF diet both neoadjuvantly (for 2 weeks prior to treatment) and adjuvantly (during treatment with radiation). Arm B (N=7) received standard oncologic treatment including a regular diet (50-52% carbohydrates, 30% fats, and 18-20% proteins). Feasibility outcomes, including recruitment, retention, intervention adherence, and safety were tracked weekly. Biomarkers, tumor progression, nutritional status, body composition, QOL, and symptoms were assessed at baseline, 2-weeks, and 2-3 months post-treatment. A control group (N=26) included HNSCC patients who follow the same applicable eligibility criteria and did not receive any kind of dietary intervention. Medical information were collected retrospectively from the control group patients' files. Information on demographics (age, sex, smoking status, weight, height, marital status, education, occupation, and residency), tumor site, cancer stage, treatment dose reduction, treatment break, early cessation of treatment, hospitalization, symptoms, and weight loss, were collected during treatment from arms A and B and retrospectively from the control group. This proposed pilot/feasibility study is the first step in determining if a CRHF diet is an effective treatment modality in cancer and if providing a diet with any composition before and during treatment is more beneficial than not providing a diet at all.

Official Title
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Feasibility of a Carbohydrate-restricted, High-fat Diet to Improve Outcomes in Head and Neck Squamous Cell Carcinoma: A Pilot Randomized Controlled Feeding Trial

Conditions
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Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Behavioral: Carbohydrate-restricted, high-fat diet
* Behavioral: Regular composition diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed with non-metastatic cancer of the oral cavity, hypopharynx, oropharynx, or larynx Plan to receive definitive radiation treatment at Augusta Victoria Hospital (AVH) in East Jerusalem Age > 18 Karnofsky Index of ≥70 % Normal liver and kidney function tests Able to understand and willingly sign a written informed consent document Lives in the West Bank or Gaza Has an oven/microwave and a refrigerator where they are staying Cancer stage 1-4 with no metastasis BMI > 20 kg/m² Exclusion Criteria: Those who do not meet the inclusion criteria Have metastatic disease Will receive a palliative treatment On insulin treatment or other diabetic treatment Uncontrolled illness (e.g. active infection, symptomatic CHF, cardiac arrhythmia, or psychiatric illness) Received previous treatment for another primary cancer Diagnosed with an illness that requires dietary modifications (e.g. renal disease, liver disease, celiac disease, and inflammatory bowel disease) Already consuming a carbohydrate-restricted, high-fat diet On chronic system corticosteroids for any reason (inhaled corticosteroids are allowed); Pregnant or lactating women Body mass index (BMI) < 20 Will start treatment within <2 weeks from screening day Requires parenteral nutrition

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>The experimental arm (N=6) were provided a CRHF diet with enough calories to maintain body weight for appoximately 2 weeks neoadjuvantly (during radiotherapy preparation) and adjuvantly during primary oncology treatment for  6.5 weeks. The CRHF diet was composed of 45% fats (mostly) unsaturated fats, 25% proteins, and 30% carbohydrates. | Behavioral: Carbohydrate-restricted, high-fat diet<br>* Diet composition was  45% fats,  30% carbohydrates, and  25% proteins. Calorie needs were provided according to what the Bioelectrical Impedance (BIA) device gave as required to maintain bodyweight. Sources of macronutrients: Carbohydrates: from whole grains, dairy products, legumes, fruits, and vegetables. Fats: from mono- and polyunsaturated fatty acids, including medium- and long-chain fatty acids. Proteins: plant-based proteins and lean animal-based proteins. All meals were provided to the participants throughout the study period and the diet was provided orally unless the patient was on a feeding tube or a feeding tube is ordered by a physician during the study period. Diet texture was according to patients chewing and swallowing abilities. If the patient is on a feeding tube or intake is insufficient, a formula with similar macronutrient composition + a protein supplement was provided.<br>* Other names: CRHF diet;|
| Active Comparator: Arm B<br>Arm B (N=7) were provided a regular composition diet prescribed with enough calories to maintain body weight for approximately 2 weeks neoadjuvantly (during radiotherapy preparation) and adjuvantly during primary oncology treatment for  6.5 weeks. The regular composition diet was composed of  50-52% carbohydrates,  30% fats, and 18-20% proteins, | Behavioral: Regular composition diet<br>* The regular composition diet contained approximately 50-52% carbohydrates, 30% fats, and 18-20% proteins<br>|
| No Intervention: Control group<br>The control group (N=26) followed applicable eligibility criteria but did not receive any intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility measure: Recruitment | Recruitment will be measured by recording the number of patients screened, included, excluded, dropped-out, and completed the study throughout the study period. | Through study completion, an average of 2 years | 
| Feasibility measure: Adherence | Adherence will be measured by collecting daily food surveys that ask about daily food intake (checking the food items that have been consumed and providing information about any other additional foods that were consumed) as well as completing all study activities which are listed on a checklist. | Throughout the 16.5 week study period (from baseline till the end of study) | 
| Feasibility measure: Retention | Retention will be measured by recording the number of patients included or agreed to participate and completed all study protocol. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Blood Glucose | Blood glucose level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Complete blood count (CBC) | CBC levels were measured, recorded, and mentioned whether levels were normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Liver function | Liver function tests were measured, recorded, and mentioned whether levels were normal, low, or high. These tests were done to assess whether liver function remained normal after consuming the diet or not. That was done by measuring the levels of GOT, GPT, and alkaline phosphatase in the blood and recording whether they were normal or not. | Throughout the 8.5 weeks of intervention | 
| Kidney function | Kidney function tests were measured, recorded, and mentioned whether levels were normal, low, or high. These tests were done to assess whether kidney function remained normal after consuming the diet or not. That was done by measuring the levels of BUN, creatinine, and uric acid in the blood and recording whether they were normal or not. | Throughout the 8.5 weeks of intervention | 
| Potassium | Potassium level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Phosphorus level was measured, recorded, and mentioned whether the level was normal, low, or high. | Phosphorus | Throughout the 8.5 weeks of intervention | 
| Magnesium | Magnesium level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Sodium | Sodium level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Chloride | Chloride level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Calcium | Calcium level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Albumin level | Albumin level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| C-reactive protein (CRP) level | CRP level was measured, recorded, and mentioned whether the level was normal, low, or high. High level indicates inflammation. | Throughout the 8.5 weeks of intervention | 
| Total protein level | Total protein level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Insulin level | Insulin level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Triglycerides level | Triglycerides levels were measured, recorded, and mentioned whether the levels were normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| Total cholesterol level | Total cholesterol level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| LDL-cholesterol level | LDL-cholesterol level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 
| HDL-cholesterol level | HDL-cholesterol level was measured, recorded, and mentioned whether the level was normal, low, or high. | Throughout the 8.5 weeks of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor progression assessment | Tumor progression was assessed using RECIST and WHO criteria as well as diagnostic CTScan/ PETScan imaging. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Nutritional status assessment | Nutritional status was assessed using the Patient generated subjective global assessment (PG-SGA) tool. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Percentage of body fat | The percentage of body fat was measured by using a Bioelectric Impedance Analysis (BIA) device and used to study the effect of the intervention on body composition. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Percentage of lean body mass | The percentage of lean body mass was measured by using a Bioelectric Impedance Analysis (BIA) device and used to study the effect of the intervention on body composition. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Percentage of body water | The percentage of body water was measured by using a Bioelectric Impedance Analysis (BIA) device and used to study the effect of the intervention on body composition. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Basal metabolic rate (BMR) | BMR was measured by using a Bioelectric Impedance Analysis (BIA) device and used to study the effect of the intervention on body composition. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Quality of life assessment | Quality of life was assessed using EORTC QLQ questionnaires. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Symptom burden assessment | Symptom burden was assessed using the validated Memorial Symptom Assessment Survey. | Throughout 16.5 week study period (from baseline till the end of study) | 
| Hospitalization | We recorded whether the participant was hospitalized or not. | Throughout the 8.5 weeks of intervention | 
| Number of hospitalizations | If the participant was hospitalized, we recorded the number of hospitalizations | Throughout the 8.5 weeks of intervention | 
| Duration of hospitalization | If the participant was hospitalized, we recorded the duration of each hospitalization | Throughout the 8.5 weeks of intervention | 
| Weight loss | We recorded whether the participant had weight loss or not | Throughout 16.5 week study period (from baseline till the end of study) | 
| Amount and span of weight loss | If the participant had weight loss, we recorded how much he had lost and during what time span | Throughout 16.5 week study period (from baseline till the end of study) | 
| Treatment dose reduction | We recorded whether there was treatment dose reduction and the reason for that. | Throughout the 6.5 weeks of treatment | 
| Treatment break | We recorded whether there was treatment break and the reason for that. | Throughout the 6.5 weeks of treatment | 
| Early cessation of treatment | We recorded whether there was early cessation of treatment and the reason for that. | Throughout the 8.5 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-metastatic