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

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

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Behavioral: Carbohydrate-restricted, high-fat diet; Behavioral: Regular composition diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Palestinian Territory, occupied
  • East Jerusalem, Palestinian Territory, occupied
    • Augusta Victoria Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Newly diagnosed with non-metastatic cancer of the oral cavity, hypopharynx, oropharynx, or larynx
2. Plan to receive definitive radiation treatment at Augusta Victoria Hospital (AVH) in East Jerusalem
3. Age > 18
4. Karnofsky Index of ≥70 %
5. Normal liver and kidney function tests
6. Able to understand and willingly sign a written informed consent document
7. Lives in the West Bank or Gaza
8. Has an oven/microwave and a refrigerator where they are staying
9. Cancer stage 1-4 with no metastasis
10. BMI > 20 kg/m²

Exclusion Criteria:

1. Those who do not meet the inclusion criteria
2. Have metastatic disease
3. Will receive a palliative treatment
4. On insulin treatment or other diabetic treatment
5. Uncontrolled illness (e.g. active infection, symptomatic CHF, cardiac arrhythmia, or psychiatric illness)
6. Received previous treatment for another primary cancer
7. Diagnosed with an illness that requires dietary modifications (e.g. renal disease, liver disease, celiac disease, and inflammatory bowel disease)
8. Already consuming a carbohydrate-restricted, high-fat diet
9. On chronic system corticosteroids for any reason (inhaled corticosteroids are allowed);
10. Pregnant or lactating women
11. Body mass index (BMI) < 20
12. Will start treatment within <2 weeks from screening day
13. Requires parenteral nutrition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; 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; 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.; Other Names: CRHF diet
Active Comparator: Arm B; 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; The regular composition diet contained approximately 50-52% carbohydrates, 30% fats, and 18-20% proteins
No Intervention: Control group; The control group (N=26) followed applicable eligibility criteria but did not receive any intervention.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Illinois at Urbana-Champaign
• Collaborators: Augusta Victoria Hospital, East Jerusalem
• Investigators: Principal Investigator: Anna E Arthur, PhD, MPH, University of Illinois at Urbana-Champaign

Publications and helpful links

General Publications

• Arthur AE, Goss AM, Demark-Wahnefried W, Mondul AM, Fontaine KR, Chen YT, Carroll WR, Spencer SA, Rogers LQ, Rozek LS, Wolf GT, Gower BA; University of Michigan Head and Neck SPORE Program. Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: results from a prospective cohort study. Int J Cancer. 2018 Sep 1;143(5):1105-1113. doi: 10.1002/ijc.31413. Epub 2018 Apr 17.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2020
• Primary Completion (Actual): August 10, 2021
• Study Completion (Actual): August 10, 2021

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 31, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: non-metastatic
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: 19635

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No