Reducing Insulin, Growth Hormones, and Tumors (RIGHT)

August 8, 2019 updated by: Fred Hutchinson Cancer Center

The Impact of Diet Quality on Biomarkers Associated With Lung Cancer Outcomes: Reducing Insulin, Growth Hormones, and Tumors (RIGHT Study)

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Little is known about the role of diet in the treatment of lung and other cancers, yet physicians are constantly confronted with the question 'what should I eat' by their patients. Very few randomized controlled dietary interventions have been carried out in this population, hence physicians and dietitians must use their best professional judgement to provide nutrition advice to their patients. Because most believe that nutrition is an important part of the treatment process, patients are eager to implement dietary recommendations and take control of this portion of their medical care. As such, upwards of 64% of patients use the internet to access health information related to cancer treatment with nutrition websites being among the most popular sites visited. However, the dietary advice on the internet aimed at cancer patients is highly discrepant, and even so among cancer treatment centers and research institutions. Within the National Comprehensive Cancer Network (NCCN), of which Fred Hutchinson is a member, only 43% (9 of 21 centers) either provide nutritional information on their website or linked to outside websites. Of those, roughly half recommended a low-fat diet during cancer treatment and the other half recommended a calorie-dense eating plan with the inclusion of high-fat foods. Clearly, this presents a potential pitfall for patients as they, without guidance from their physician or dietitian, may follow dietary advice that is misleading or potentially harmful.

While there is a need for further studies to elucidate the role diet plays during the treatment of cancers in general, lung cancer in particular is understudied in comparison to other types of cancers, and presents a unique opportunity to study the impact of diet during treatment. Primarily, lung cancer patients do not typically suffer from constraints to eating that affect colorectal, esophageal, or head/throat/neck cancer sufferers. Therefore, diet interventions using whole-foods may be fairly well tolerated in this population. A review of nutrition interventions in lung cancer patients carried out through October 2012 indicated that only three controlled studies in 149 patients had been completed, all of which used nutritional supplement products to prevent unintentional weight loss. The authors concluded that nutrition interventions in this population are safe and that more research is needed to determine optimal nutrition recommendations for advanced, inoperable lung cancers

. Through the manipulation of diet, it is possible to selectively target key pathways involved in cancer growth and proliferation. For instance, it is known that cancer cells generate energy through the process of anaerobic glycolysis (the Warburg Effect) which relies primarily on glucose as a fuel source. Evidence from in vitro studies of non-small cell lung cancer (NSCLC) suggests that reducing the glucose availability from the diet might be particularly effective in the treatment of squamous cell carcinomas because the glucose transporter (GLUT-1) expression is markedly elevated in these cancer cells and is associated with enhanced uptake of, and dependence upon, glucose. Case-control studies show that dietary glycemic index is strongly associated with squamous cell carcinoma among NSCLC patients, suggesting that dietary strategies that limit carbohydrate may be effective in 'starving' these predominately glycolytic cells. A diet pattern in which overall energy is not limited, but sources of glucose are selectively reduced, is one mechanism by which cancer progression might be abated. Such low-carbohydrate or - in their most extreme form - ketogenic diets, which provide energy primarily from fat and protein while minimizing carbohydrates, are increasingly shown to be therapeutic for the treatment of glioblastoma and other cancers, as well as neurological diseases, including epilepsy, and cardiovascular disease risk factors.

It is also known that activation of the IGF pathway is critical for tumor cell proliferation, invasiveness, and survival in NSCLC and downregulation of this pathway through dietary manipulation might also be an effective means to suppress cancer growth. The insulin-like growth factor-1 receptor (IGF-1R) is abundantly present on surfaces of tumor cells, and high circulating levels of IGF-1, the ligand for the IGF-1R, are a risk factor for future lung malignancy. As individuals who consume diets high in protein from animal sources have greater levels of circulating IGF-1 compared to those consuming a vegetarian/vegan diet, limiting the intake of animal products may be an intriguing dietary strategy that might influence cancer progression. In our lab, we have shown that insulin sensitivity and glucose tolerance improved after subjects adhered to a diet rich in whole grains, legumes, fruits, and vegetables, that excluded refined sources of energy (added sugar, refined grains, added fats and oils) (Kratz et al. unpublished data). This suggests that such a diet would also reduce the diurnal exposure of tumor cells to both glucose and insulin, which would decrease the availability of fuel and growth hormones for cancer cells. Taken together, both low-carbohydrate/ketogenic diets and low-fat, whole foods plant-based diets could plausibly affect pathways involved in cancer growth or progression by minimizing diurnal exposure to glucose, insulin, and IGF-1.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Center Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Diet A (low carbohydrate)
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)
Receive dietary guidelines and recipes and consume a low-carbohydrate diet
Other Names:
  • DIET
  • Special Diet Therapy
Experimental: Diet B (low fat)
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)
Receive dietary guidelines and recipes and consume a low-fat diet
Other Names:
  • DIET
  • Special Diet Therapy
Active Comparator: Diet C (USDA control)
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)
Receive dietary guidelines and recipes and consume USDA control diet
Other Names:
  • DIET
  • Special Diet Therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The impact of diet on IL-6
Time Frame: 24 weeks
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
Time Frame: 24 weeks
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
Time Frame: 24 weeks
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
Time Frame: 24 weeks
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
Time Frame: 24 weeks
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
Time Frame: 24 weeks
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
Time Frame: 24 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in body weight
Time Frame: 24 weeks
To compare the impact of consuming the three study diets for 24 weeks on body weight.
24 weeks
Change in compliance
Time Frame: Baseline up to 52 weeks
To assess the degree of dietary adherence to the three study diets at 12 weeks and 24 weeks following the initiation of the intervention. Dietary compliance measurement: macronutrient intakes (FFQ) within 10% of total energy intake targets
Baseline up to 52 weeks
Response rate
Time Frame: At 12 and 24 weeks
Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.
At 12 and 24 weeks
Progression-free survival
Time Frame: Up to 1 year
Will be assessed by Kaplan-Meier curves.
Up to 1 year
Overall survival
Time Frame: Up to 1 year
Will be assessed by Kaplan-Meier curves.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fred Hutchinson Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mario Kratz, Fred Hutchinson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 21, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 5, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 5, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 20, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 21, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 24, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 12, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 8, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RG1001909
  • 8680 (FHCRC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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