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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Cystic Fibrosis-related Diabetes; Cystic Fibrosis With Intestinal Manifestations
• Intervention / Treatment: Behavioral: Low Glycemic Load Diet

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kevin J Scully, MB, BCh, BAO; Phone Number: 617-355-7476; Email: kevin.scully@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of CF
2. Diagnosis of pancreatic insufficiency, requiring pancreatic enzyme replacement
3. 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
4. BMI 21-25 kg/m2
5. 18 years and above

Exclusion Criteria:

1. Current use of insulin
2. Most recent HbA1c ≥6.5%
3. History of solid organ transplant or currently listed for solid organ transplant
4. FEV1 <50% predicted on most recent pulmonary function testing
5. Currently receiving enteral nutrition support
6. Current or anticipated pregnancy in the next 1 year
7. Hospitalization for CF exacerbation within 1 month of enrollment
8. Started or stopped treatment with Trikafta or other CFTR modulator within 3 months of enrollment
9. Currently adhering to a low glycemic index or other carbohydrate restricted diet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Investigators: Principal Investigator: Melissa S Putman, MD,MS, Boston Children's Hospital; Massachusetts General Hospital

Publications and helpful links

General Publications

• Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, Robinson KA, Sabadosa KA, Stecenko A, Slovis B; CFRD Guidelines Committee. Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care. 2010 Dec;33(12):2697-708. doi: 10.2337/dc10-1768. No abstract available.
• Gabel ME, Galante GJ, Freedman SD. Gastrointestinal and Hepatobiliary Disease in Cystic Fibrosis. Semin Respir Crit Care Med. 2019 Dec;40(6):825-841. doi: 10.1055/s-0039-1697591. Epub 2019 Oct 28.
• Prentice BJ, Ooi CY, Strachan RE, Hameed S, Ebrahimkhani S, Waters SA, Verge CF, Widger J. Early glucose abnormalities are associated with pulmonary inflammation in young children with cystic fibrosis. J Cyst Fibros. 2019 Nov;18(6):869-873. doi: 10.1016/j.jcf.2019.03.010. Epub 2019 Apr 26.
• Brennan AL, Gyi KM, Wood DM, Johnson J, Holliman R, Baines DL, Philips BJ, Geddes DM, Hodson ME, Baker EH. Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis. J Cyst Fibros. 2007 Apr;6(2):101-9. doi: 10.1016/j.jcf.2006.03.009. Epub 2006 Jul 17.
• Balzer BW, Graham CL, Craig ME, Selvadurai H, Donaghue KC, Brand-Miller JC, Steinbeck KS. Low glycaemic index dietary interventions in youth with cystic fibrosis: a systematic review and discussion of the clinical implications. Nutrients. 2012 Apr;4(4):286-96. doi: 10.3390/nu4040286. Epub 2012 Apr 18.

Helpful Links

• CFF 2021 Patient Registry Annual Data Report

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: July 7, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Continuous Glucose Monitoring; Cystic Fibrosis Related Diabetes; Low Glycemic Load
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: P00034904

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD data with other researchers.

Drug and device information, study documents

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