FEED-Cystic Fibrosis (FEED-CF)

Study Overview
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Brief Summary
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The goal of this study is to determine the extent to which excess dietary sugars serve as a precipitating factor in glucose intolerance in adults with cystic fibrosis (CF), a population at especially high risk for a unique form of diabetes (CF-related diabetes, CFRD) and with standard-of-care dietary recommendations (high-calorie, high-fat) that conflict with recommendations for other forms of diabetes. This trial will investigate if the typical high-sugar, high-fat CF diet plays a role in diabetes risk and visceral fat accumulation in people with CF. A total of 30 participants will get a low-added sugar, high-fat diet and the other 30 will get a standard CF diet with no sugar restrictions. Participants will be randomized to the diet group they are assigned. All foods will be provided for 8 weeks.

Detailed Description
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Approximately half of adults with cystic fibrosis (CF), a genetic disease, will develop diabetes. Dietary strategies shown to be successful in preventing or treating other forms of diabetes in people without CF contradict current nutritional recommendations for people with CF. The nutrition standard-of-care in CF is prescription of an unrestricted high-calorie, high-fat diet because of malnutrition. However, the standard CF diet translates to low-quality diets, with excess added sugars well-above general population recommendations. Also the investigators have shown that people with CF have more fat around their abdominal organs (called visceral fat) compared to healthy controls. The hypothesis is that the typical high-sugar, high-fat CF diet plays a role in diabetes risk and visceral fat accumulation in people with CF. In this study, the investigators will test if a low-added sugar diet improves risk markers for diabetes and decreases visceral fat over 8 weeks. The study will recruit 60 participants with CF. A total of 30 participants will get a low-added sugar, high-fat diet and the other 30 will get a standard CF diet with no sugar restrictions. Participants will be randomized to the diet group they are assigned. All foods will be provided for 8 weeks. There will be a total of 4 study visits at the Emory Hospital clinical research unit. These will include: 1) a screening visit with an oral glucose tolerance test with blood draws to determine if they already have diabetes, 2) a baseline visit for an insulin secretion test (called glucose-potentiated arginine (GPA) stimulation test) to assess risk for diabetes, as well as magnetic resonance imaging (MRI) testing to measure visceral fat, 3) a 4-week visit for another oral glucose tolerance test and in-person check-in, and 4) an 8-week visit for another GPA and MRI. Blood samples will be collected and banked. In addition to all meals provided for 8 weeks, participants will be compensated for their time and effort. Participants will be recruited from patients seen at the Emory CF Clinic. Informed consent will be performed prior to any study testing. The investigators hope this study will contribute to the development of new standardized nutrition guidelines for people living with CF.

Official Title
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Feeding Study to Optimize Endocrine Dysfunction in Cystic Fibrosis

Conditions
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Cystic Fibrosis, Cystic Fibrosis-related Diabetes

Intervention / Treatment
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* Other: Low-added sugar, high-fat diet
* Other: High-added sugar, high-fat CF diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed CF diagnosis based on sweat chloride concentration using pilocarpine iontophoresis and/or CFTR genotyping showing two disease causing mutations Exocrine pancreatic insufficiency Ages 18 years and older Baseline estimated daily total added sugar intake >16 tsp, as estimated from the Dietary Screener Questionnaire (DSQ) or a 3-day food record Exclusion Criteria: Nocturnal tube feeds BMI <18.5 kg/m2 Life expectancy < 12 months On waiting list for organ transplantation Confirmed diagnosis of CFRD Screening OGTT showing fasting hyperglycemia (≥126 mg/dL) Chronic oral steroid use Current pregnancy or lactation or plans to become pregnant during study period Inability/unwillingness to consume the majority of foods on the menu during the study period MRI-incompatible metal that cannot be removed for testing Uncontrolled exocrine pancreatic insufficiency/malabsorption Clinically instability, defined as no changes in medical regimen (including medications and pulmonary exacerbations) for at least 21 days prior to study visit (May rescreen at later date) Initiation of CFTR modulator within previous 8 weeks OR unstable changes in weight and lung function due to CFTR modulator use (May re-screen at later date) Actively trying to gain or lose weight (May re-screen at a later date) Any food allergies or intolerances that cannot be accommodated

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A double-blind, randomized, parallel-group design clinical trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-added sugar, high-fat diet Arm<br>Patients will receive a low-added sugar, high-fat diet for 8 weeks. Study menus will be designed by registered dietitians using the Nutrient Database System for Research (NDSR) software program with a 2-wk rotation.Total kcal provided will be individually tailored to maintain body weight and adjusted throughout as needed. All foods (including snacks and drinks) for 8 wks will be delivered to participants' homes. Menus will be designed so that food will be delivered to subjects' homes every 3-4 days. It will be expected that participants consume only the foods provided by the study. | Other: Low-added sugar, high-fat diet<br>* Consist of <5% kcal from added sugars as recommended by the American Heart Association, and the glycemic index will be 45 or lower (25% lower than typical CF diet). The macronutrient composition of both study diets will reflect the general CF recommendations for macronutrients: 35-40% of total kcal from fat and 15-20% total kcal from protein.<br>|
| Active Comparator: Typical CF diet Arm<br>Patients will receive a high-added sugar, high-fat CF diet for 8 weeks. Study menus will be designed by registered dietitians using the Nutrient Database System for Research (NDSR) software program with a 2-wk rotation. Total kcal provided will be individually tailored to maintain body weight and adjusted throughout as needed. All foods (including snacks and drinks) for 8 wks will be delivered to participants' homes. Menus will be designed so that food will be delivered to subjects' homes every 3-4 days. It will be expected that participants consume only the foods provided by the study. | Other: High-added sugar, high-fat CF diet<br>* Consist of ≥13% kcal from added sugars and the glycemic index will be >60. The macronutrient composition of both study diets will reflect the general CF recommendations for macronutrients: 35-40% of total kcal from fat and 15-20% total kcal from protein.<br>* Other names: Typical CF diet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in acute insulin response to arginine (AIRarg) from baseline | Participants will undergo a Glucose-Potentiated Arginine Stimulation (GPA) Test after a 10-12 hour overnight fast to measure acute insulin (AIRarg) responses during a 230 and 340 mg/dl glucose clamp. This test will measure changes in beta cell secretory capacity. | Baseline and 8 weeks post intervention | 
| Change in acute C-peptide (ACRarg) from baseline | Participants will undergo a Glucose-Potentiated Arginine Stimulation (GPA) Test after a 10-12 hour overnight fast to measure acute C-peptide (ACRarg) responses during a 230 and 340 mg/dl glucose clamp. This test will measure changes in beta cell secretory capacity. | Baseline and 8 weeks post intervention | 
| Change in visceral adipose tissue from baseline | Dual energy X-ray absorptiometry (DEXA)-derived measurement of visceral adipose tissue (VAT) will be assessed with a GE Lunar iDXA machine. This will enable assessment of changes in body composition over the study. | Baseline and 8 weeks post intervention | 
| Change in fasted plasma Eh[CySS] from baseline | Change in plasma Cysteine/Cystine Redox Potential (Eh[CySS]) will be measured. | Baseline and 8 weeks post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gastrointestinal Symptom Rating Scale (GSRS) scale | The GSRS is a 15 items combine into five symptom clusters: Reflux, Abdominal pain, Indigestion, Diarrhea and Constipation. Possible score range is 0-7, with 7 being the worst and 0 being the best (no symptoms). | Baseline and 8 weeks post intervention | 
| Change in hepatic and pancreatic fat volume | Dual energy X-ray absorptiometry (DEXA)-derived measurement of visceral adipose tissue (VAT) for hepatic and pancreatic fat volume. Will be assessed with a GE Lunar iDXA machine. | Baseline and 8 weeks post intervention | 
| Change in fasted plasma Eh[GSSG] | Change in plasma glutathione disulfide (GSSG) (Eh[CySS]) will be measured. | Baseline and 8 weeks post intervention |