Reducing Insulin, Growth Hormones, and Tumors

NCT03785808 | Terminated DMC

• 2 other identifiers: RG10019098680
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this project is to compare the effect of two widely implemented cancer diets, differing drastically in macronutrient content, on biomarkers of inflammation, compared to a control diet. Diet A will be a low-carbohydrate, high-fat ketogenic-type diet with an emphasis on whole foods. By limiting carbohydrate, the diet will have an extremely low glycemic load, thereby minimizing diurnal glucose and insulin excursions. Diet B will be a low-fat, high-carbohydrate whole foods plant-based diet. It will include only fiber-rich, low-glycemic index sources of carbohydrates and largely eliminate animal protein, which will minimize rapid spikes in blood glucose and insulin and the production of IGF-1. This diet is also hypothesized to improve glucose tolerance and insulin sensitivity, which should further help minimize diurnal glycemic and insulinemic excursions. Both diets will be compared to a control diet based on the 2015 USDA Dietary Guidelines for Americans (Diet C) in patients suffering from advanced lung cancer as they are completing medical therapy. The overarching hypothesis motivating this work is that a nutrient dense diet that minimizes known factors involved in tumor growth and progression may improve the effectiveness of therapy. Our specific hypothesis is that participants following either of the experimental diets, A or B, will experience a reduction in biomarkers of insulin resistance and chronic inflammation, both of which are known risk factors for progression in lung cancer, and a greater median time to progression compared to those on the control diet (Diet C).

Conditions

Diet Modification; Lung Cancer

Keywords

ketogenic diet; low-fat diet

Outcome Measures

Primary Outcomes (7)

• The impact of diet on IL-6

  To compare the impact of consuming the three study diets for 24 weeks on the pro-inflammatory mediator IL-6, which is associated with lung cancer progression.

  24 weeks

• The impact of diet on hsCRP

  To compare the impact of consuming the three study diets for 24 weeks on the pro-inflammatory mediator hsCRP, which is associated with lung cancer progression.

  24 weeks

• The impact of diet on adiponectin

  To compare the impact of consuming the three study diets for 24 weeks on the pro-inflammatory mediator adiponectin, which is associated with lung cancer progression.

  24 weeks

• The impact of diet on HOMA-IR

  To compare the impact of consuming the three study diets for 24 weeks on the homeostasis model assessment insulin resistance (HOMA-IR) index, which is associated with lung cancer progression.

  24 weeks

• The impact of diet on the Glasgow Prognostic Score for cancer outcomes

  To compare the impact of consuming the three study diets for 24 weeks on the Glasgow Prognostic Score, which is associated with lung cancer outcomes.

  24 weeks

• The impact of diet on IGF-1

  To compare the impact of consuming the three study diets for 24 weeks on circulating levels of IGF-1, which is associated with lung cancer progression.

  24 weeks

• The impact of diet on IGFBP-3

  To compare the impact of consuming the three study diets for 24 weeks on circulating levels of IGFBP-3, which is associated with lung cancer progression.

  24 weeks

Secondary Outcomes (5)

• Change in body weight

  24 weeks

• Change in compliance

  Baseline up to 52 weeks

• Response rate

  At 12 and 24 weeks

• Progression-free survival

  Up to 1 year

• Overall survival

  Up to 1 year

Study Arms (3)

Diet A (low carbohydrate)

EXPERIMENTAL

Dietary Intervention A will be a low-carbohydrate/high fat, ketogenic-type diet. The diet will include salads, leafy green and non-starchy vegetables, nuts and seeds, eggs, fish and shellfish, and meats in most meals. Grains and added sugars will be excluded, and starchy vegetables, fruits, berries, and legumes will be limited to below 10% of total calorie intake. In addition full fat yogurt, cheeses, and butter will be allowed in moderate amounts. Participants will be encouraged to eat freely from whole-foods rich in fats such as avocados, nuts, seeds, olives, coconut and to use coconut, medium-chain triglyceride (MCT), olive, and avocado oils for cooking and baking on that diet. Participants will aim to fulfill at least 65% of their total calorie requirements from fats.

Behavioral: Special Diet Therapy (low-carb)

Diet B (low fat)

EXPERIMENTAL

Dietary Intervention B will be low-fat, high carbohydrate whole-foods, plant-based diet. Most animal products and concentrated plant-based protein sources (such as soy isolates) will be excluded. Whole grains, particularly in their cooked form, legumes, vegetables, and fruits will be encouraged while excluding added sugars and refined grains. Added fats and oils will be discouraged on this diet as dietary fat should comprise less than 10% of total energy. Participants can eat freely from all types of fruits, vegetables, and cooked whole grains. Legumes will be emphasized as a replacement for meat and dairy products. Proteins similar to beef, pork, poultry, and dairy products, should be strictly limited, while lean proteins such as eggs, fish, and shellfish may be included occasionally.

Behavioral: Special Diet Therapy (low-fat)

Diet C (USDA control)

ACTIVE COMPARATOR

The control dietary intervention will be based on the 2015 USDA Dietary Guidelines for Americans, with a slightly higher amount of protein than recommended for the general population, and will be comprised of grains (of which \~50% should be consumed as whole grains), 3 servings per day of non-fat or low-fat dairy, legumes, fruit, vegetables, fish, vegetable oils and margarines, and limited quantities of meat, eggs, added sugars, nuts/seeds. Participants will be encouraged to reduce sodium intake to less than 2300 mg (1500 mg for participants over 51 yrs. old) per day, and to consume less than 10% of calories from saturated fat.

Behavioral: Special Diet Therapy (USDA control)

Interventions

Special Diet Therapy (low-carb) BEHAVIORAL

Receive dietary guidelines and recipes and consume a low-carbohydrate diet

Also known as: DIET, Special Diet Therapy

Diet A (low carbohydrate)

Special Diet Therapy (low-fat) BEHAVIORAL

Receive dietary guidelines and recipes and consume a low-fat diet

Also known as: DIET, Special Diet Therapy

Diet B (low fat)

Special Diet Therapy (USDA control) BEHAVIORAL

Receive dietary guidelines and recipes and consume USDA control diet

Also known as: DIET, Special Diet Therapy

Diet C (USDA control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (18 years or older) receiving treatment at the Seattle Cancer Care Alliance (SCCA)
• Stage IIIB and IV non-small cell adenocarcinoma or squamous cell carcinoma, or small cell lung cancer with advanced disease receiving therapy with systemic treatment
• Body mass index (BMI) \>= 20 kg/m\^2
• Body weight within 10% of current weight within the 3 months before starting the study
• Able and willing to attend bi-weekly dietary support sessions at the Seattle Cancer Care Alliance (SCCA) during the initial 12-week intervention period
• Willing and able to follow the dietary regimen
• Willing to maintain usual lifestyle habits (other than diet) throughout the study (e.g., physical activity habits)
• Ability to understand, speak, and write in English
• Ability to provide informed written consent

You may not qualify if:

• Neuroendocrine large cell carcinoma or atypical carcinoids with metastatic disease
• Small cell lung cancer receiving curative therapy with radiation
• Use of antidiabetic medications or insulin within the last 6 months
• Presence of grade 2 weight loss, cachexia, and/or severe nausea
• Current participation in therapeutic first line trial
• Alcohol intake \> 2 drinks per day
• Major dietary restriction, as determined by the researcher
• Other significant health condition as determined by the researcher

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Seattle Cancer Center Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Diet; Diet, Fat-Restricted

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet Therapy; Nutrition Therapy; Therapeutics

Study Officials

• Mario Kratz

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be randomized to the low-carbohydrate diet (Diet A), the low-fat diet (Diet B), or the USDA control diet (Diet C). Participants will not be informed about the nature of the intervention diets or the hypotheses we aim to test. The participants will know the diets only as "Diet A", "Diet B", and "Diet C". They will be de-briefed about the nature of the diets and our hypotheses by mail after the study has been completed. At that time, we will also offer them a folder with the dietary guidelines and recipes for the diets they had not been randomized to. The reason participants will be blinded about the diets is that knowing the details may create a placebo effect and/or opting into another intervention diet.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2018
• First Posted: December 24, 2018
• Study Start: December 21, 2018
• Primary Completion: August 5, 2019
• Study Completion: August 5, 2019
• Last Updated: August 12, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)