A Pilot Study of a Low Glycemic Load Diet in Adults With Cystic Fibrosis

Study Overview
=================
Brief Summary
-----------------
This pilot study will evaluate the safety and tolerability of a low glycemic load dietary intervention in adult patients with cystic fibrosis (CF) in a rigorous feeding study. Specific emphasis will be placed on changes in weight, body composition, and glycemic measures obtained via continuous glucose monitor (CGM) usage.

Detailed Description
-----------------
Non-pulmonary complications of cystic fibrosis (CF) are becoming increasingly prevalent with the changing landscape of CF care. CF related diabetes mellitus (CFRD) and CF related gastrointestinal (GI) complications have significant effects on morbidity and mortality. Treatment options are limited to insulin therapy for CFRD and symptom control for most GI complications. BMI is a well-established marker of morbidity and mortality in patients with CF. Many patients consume a high carbohydrate intake to meet their increase caloric needs, potentially leading to complications including post-prandial hyperglycemia, increased inflammation, and abnormal GI motility. Dietary recommendations for children and adults with CF are limited and based entirely on consensus and expert opinion. As patients with CF live longer with highly effective modulator therapy, it is important to understand the effects of dietary composition on short and long-term endocrine, GI, and pulmonary outcomes. The investigators will conduct a prospective, open-label pilot study in adults with CF and impaired glucose tolerance or indeterminate glycemia to establish the safety and tolerability of a low glycemic load (LGL) diet. Subjects will initially follow their standard diet for a 2-week run-in period, then transition to a LGL diet provided by a food delivery service for the remaining 8 weeks. The investigators will also investigate potential short-term outcomes of dietary carbohydrate manipulation, including glycemic variability measured by continuous glucose monitor (CGM), body composition via DXA, GI symptoms, and quality of life measures. The investigators hypothesize that a diet lower in carbohydrate content will be safe, tolerable, and associated with weight maintenance or gain, and that a LGL diet will result in decreased glycemic variability via CGM, improved GI symptoms, increased lean to fat mass ratio, and improved quality of life measures over an 8-week period.

Official Title
-----------------
A Pilot Study to Test the Safety and Tolerability of a Low Glycemic Load Dietary Intervention in Adults With Cystic Fibrosis

Conditions
-----------------
Cystic Fibrosis, Cystic Fibrosis-related Diabetes, Cystic Fibrosis With Intestinal Manifestations

Intervention / Treatment
-----------------
* Behavioral: Low Glycemic Load Diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of CF Diagnosis of pancreatic insufficiency, requiring pancreatic enzyme replacement Oral glucose tolerance test within the past three years showing impaired glucose tolerance (2-hour glucose ≥140 mg/dL) or indeterminate glycemia (1-hour glucose ≥200), HbA1c 5.7-6.4% in the past one year, and/or or documented random glucose ≥200 in the past one year BMI 21-25 kg/m2 18 years and above Exclusion Criteria: Current use of insulin Most recent HbA1c ≥6.5% History of solid organ transplant or currently listed for solid organ transplant FEV1 <50% predicted on most recent pulmonary function testing Currently receiving enteral nutrition support Current or anticipated pregnancy in the next 1 year Hospitalization for CF exacerbation within 1 month of enrollment Started or stopped treatment with Trikafta or other CFTR modulator within 3 months of enrollment Currently adhering to a low glycemic index or other carbohydrate restricted diet

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single dietary treatment arm with run-in period as a control
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Glycemic Load Diet<br>Feeding study with dietary composition (approximately) 50% fat, 30% carbohydrate, 20% protein. | Behavioral: Low Glycemic Load Diet<br>* Food delivery service will provide a low glycemic load diet for 8 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight from baseline and 10 weeks | Anthropometric measure | Baseline and 10 weeks | 
| Change in percent time <54 mg/dL | Continuous glucose monitoring | Baseline and 10 weeks | 
| Patient reported tolerability of dietary intervention, Likert scale | Single Likert scale question of overall diet tolerability, ranging from 1 (intolerable) to 10 (completely tolerable) | Single measurement at 10 weeks after diet completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percent time >140 mg/dL | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in CGM average glucose | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in CGM glucose management indicator (GMI) | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in CGM standard deviation (SD) | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in CGM coefficient of variation (CV) | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in percent time less than 50 mg/dL on CGM | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in percent time less than 70 mg/dL on CGM | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in percent time 70-180 mg/dL on CGM | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in percent time greater than 180 mg/dL on CGM | Continuous glucose monitoring | Baseline to 10 weeks | 
| Change in percent time greater than >250 mg/dL on CGM | Continuous glucose monitoring | Baseline to 10 weeks | 
| Number of episodes of symptomatic hypoglycemia | Survey | Baseline and 10 weeks | 
| Change in lean and fat mass | DXA body composition measures | Baseline and 10 weeks | 
| Change in Patient Assessment of Constipation (PAC) questionnaire score | Likert scale questionnaire with 12 items, each item scored 0-4, total score ranging from 0-48 with higher scores related to worse outcomes | Baseline and 10 weeks | 
| Change in Patient Assessment of Gastrointestinal Symptom (PAGI-SYM) questionnaire score | Likert scale questionnaire with 20 items, each item scored 0-5, total score ranging from 0-100 with higher scores related to worse outcomes | Baseline and 10 weeks | 
| Change in Modified Activity Questionnaire (MAQ) score | Questionnaire, units of total hours of exercise over past 12 months, no min or max scores, higher value related to better outcome | Baseline and 10 weeks | 
| Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) score | Likert scale questionnaire, 50 items, each scored 0-4, total score ranging from 0-100 with higher value reflecting better outcome | Baseline and 10 weeks | 
| Change in erythrocyte sedimentation rate (ESR) | Laboratory test, measured in mm/hr | Baseline and 10 weeks | 
| Change in c-reactive protein (CRP) | Laboratory test, measured in mg/L | Baseline and 10 weeks | 
| Change in intestinal fatty acid binding protein (I-FABP) | Laboratory test, measured in ng/mL | Baseline and 10 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cystic Fibrosis Related Diabetes, Low Glycemic Load, Continuous Glucose Monitoring