Am J Gastroenterol. 2022 Jun 1;117(6):902-917.doi: 10.14309/ajg.0000000000001800. Epub 2022 Apr 20.

Heather C Kaplan ^1 2 3, Lisa Opipari-Arrigan ^2 3 4, Jiabei Yang ⁵, Christopher H Schmid ⁵, Christine L Schuler ^3 6, Shehzad A Saeed ⁷, Kimberly L Braly ⁸, Fandi Chang ⁵, Lauren Murphy ², Cassandra M Dodds ², Mason Nuding ⁹, Hao Liu ¹⁰, Sheri Pilley ^11 12, Julie Stone ^11 13, Gisele Woodward ^11 14, Nancy Yokois ¹⁵, Alka Goyal ^16 17, Dale Lee ⁸, Ann Ming Yeh ¹⁷, Peter Lee ¹⁸, Benjamin D Gold ¹⁴, Zarela Molle-Rios ¹⁹, R Jeff Zwiener ²⁰, Sabina Ali ²¹, Mallory Chavannes ^22 23, Tiffany Linville ²⁴, Ashish Patel ^25 26, Travis Ayers ²⁷, Mikelle Bassett ²⁸, Brendan Boyle ²⁹, Pablo Palomo ³⁰, Sofia Verstraete ³¹, Jill Dorsey ³², Jess L Kaplan ³³, Steven J Steiner ³⁴, Kaylie Nguyen ³⁵, Jennifer Burgis ³¹, David L Suskind ⁸, ImproveCareNow Pediatric IBD Learning Health System

Author information

• ¹Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
• ²James M. Anderson Center for Health Systems Excellence, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
• ³Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
• ⁴Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
• ⁵Department of Biostatistics and Center for Evidence Synthesis in Health, School of Public Health, Brown University, Providence, Rhode Island, USA.
• ⁶Division of Hospital Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
• ⁷Department of Medical Affairs, Dayton Children's Hospital and Boonshoft School of Medicine, Wright State University, Dayton, Ohio, USA.
• ⁸Division of Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, Washington, USA.
• ⁹Center for Clinical and Translational Research, Seattle Children's Research Institute, Division of Gastroenterology, Seattle Children's Hospital, Seattle, Washington, USA.
• ¹⁰Division of Applied Mathematics, Brown University, Providence, Rhode Island, USA.
• ¹¹Parent Working Group, ImproveCareNow Pediatric IBD Learning Health System.
• ¹²MUSC Health Shawn Jenkins Children's Hospital, Charleston, South Carolina, USA.
• ¹³The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
• ¹⁴Division of Gastroenterology, GI Care for Kids, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
• ¹⁵Childrens Hospital of the King's Daughters, Division of Pediatric Gastroenterology, Norfolk, Virginia, USA.
• ¹⁶Division of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Hospital, Kansas City, Missouri, USA.
• ¹⁷Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Stanford University, Palo Alto, California, USA.
• ¹⁸Division of Pediatric Gastroenterology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.
• ¹⁹Division of Pediatric Gastroenterology, Nemours Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA.
• ²⁰Dell Children's Medical Group, Pediatric Gastroenterology, Dell Children's Medical Center of Central Texas, Austin, Texas, USA.
• ²¹Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UCSF Benioff Children's Hospital, Oakland, California, USA.
• ²²Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital Los Angeles, Los Angeles, California, USA.
• ²³Department of Pediatrics, University of Southern California, Los Angeles, California, USA.
• ²⁴Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Levine Children's Hospital, Charlotte, North Carolina, USA.
• ²⁵Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas, USA.
• ²⁶Pediatric Gastroenterology, Phoenix Children's Hospital, Phoenix, Arizona, USA.
• ²⁷Division of Pediatric Gastroenterology, Arkansas Children's Hospital, UAMS, Little Rock, Arkansas, USA.
• ²⁸Division of Pediatric Gastroenterology, Oregon Health Sciences University, Portland, Oregon, USA.
• ²⁹Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, Ohio, USA.
• ³⁰Division of Pediatric Gastroenterology, Nemours Children's Hospital, Orlando, Florida, USA.
• ³¹Division of Pediatric Gastroenterology, UCSF Medical Center, San Francisco, California, USA.
• ³²Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nemours Children's Specialty Care, Jacksonville, Florida, USA.
• ³³Division of Pediatric Gastroenterology, MassGeneral Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
• ³⁴Division of Pediatric Gastroenterology/Hepatology/Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA.
• ³⁵Division of Pediatric Gastroenterology, Hepatology and Nutrition, Lucile Packard Children's Hospital at Stanford, Stanford, California, USA.

Abstract

Introduction: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant's baseline, usual diet (UD).

Methods: Across 19 sites, we recruited patients aged 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets.

Results: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% credible interval -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not.

Discussion: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.

Trial registration: ClinicalTrials.gov NCT03301311.