Clinical trial NCT04519853: A Pilot Study of a Low Glycemic Load Diet in Adults With Cystic Fibrosis
Official title: A Pilot Study to Test the Safety and Tolerability of a Low Glycemic Load Dietary Intervention in Adults With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis
Cystic Fibrosis-related Diabetes
Cystic Fibrosis With Intestinal Manifestations
Keywords: Cystic Fibrosis Related Diabetes
Low Glycemic Load
Continuous Glucose Monitoring
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2020-08-20
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single dietary treatment arm with run-in period as a control
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in weight from baseline and 10 weeks
timeFrame: Baseline and 10 weeks
measure: Change in percent time <54 mg/dL
timeFrame: Baseline and 10 weeks
measure: Patient reported tolerability of dietary intervention, Likert scale
timeFrame: Single measurement at 10 weeks after diet completion
Secondary outcomes:
measure: Change in percent time >140 mg/dL
timeFrame: Baseline to 10 weeks
measure: Change in CGM average glucose
timeFrame: Baseline to 10 weeks
measure: Change in CGM glucose management indicator (GMI)
timeFrame: Baseline to 10 weeks
measure: Change in CGM standard deviation (SD)
timeFrame: Baseline to 10 weeks
measure: Change in CGM coefficient of variation (CV)
timeFrame: Baseline to 10 weeks
measure: Change in percent time less than 50 mg/dL on CGM
timeFrame: Baseline to 10 weeks
measure: Change in percent time less than 70 mg/dL on CGM
timeFrame: Baseline to 10 weeks
measure: Change in percent time 70-180 mg/dL on CGM
timeFrame: Baseline to 10 weeks
measure: Change in percent time greater than 180 mg/dL on CGM
timeFrame: Baseline to 10 weeks
measure: Change in percent time greater than >250 mg/dL on CGM
timeFrame: Baseline to 10 weeks
measure: Number of episodes of symptomatic hypoglycemia
timeFrame: Baseline and 10 weeks
measure: Change in lean and fat mass
timeFrame: Baseline and 10 weeks
measure: Change in Patient Assessment of Constipation (PAC) questionnaire score
timeFrame: Baseline and 10 weeks
measure: Change in Patient Assessment of Gastrointestinal Symptom (PAGI-SYM) questionnaire score
timeFrame: Baseline and 10 weeks
measure: Change in Modified Activity Questionnaire (MAQ) score
timeFrame: Baseline and 10 weeks
measure: Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) score
timeFrame: Baseline and 10 weeks
measure: Change in erythrocyte sedimentation rate (ESR)
timeFrame: Baseline and 10 weeks
measure: Change in c-reactive protein (CRP)
timeFrame: Baseline and 10 weeks
measure: Change in intestinal fatty acid binding protein (I-FABP)
timeFrame: Baseline and 10 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital; Massachusetts General Hospital
name: Melissa S Putman, MD,MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.