A Randomized Double-Blind Clinical Trial Comparing Mannitol-Based Regimens and Water as Oral Contrast Agents With a Psyllium Arm, for CT Enterography: Impact on Imaging Performance and Tolerability

Abstract Adequate bowel distension is critical for optimal diagnostic accuracy in computed tomography (CT) enterography (CTE). Although mannitol is commonly used as a neutral oral contrast agent, the optimal concentration remains undefined. The role of fiber adjuncts such as psyllium has not been fully explored. This randomized trial aimed to compare the efficacy and tolerability of varying mannitol concentrations with and without psyllium versus water. Three hundred patients undergoing CTE were randomized into six groups: water, 1% mannitol, 2% mannitol, 3% mannitol, 3% mannitol + post-CT water, and 3% mannitol + psyllium. Quantitative and qualitative bowel distension, fold visibility, homogeneity, and adverse events were assessed across groups. Statistical analysis was performed using “R” and statistical packages multcomp, dunn.test, ggstats2, ggstatsplot, dplyr, etc. were used to analyze and visualize the data. Continuous data of groups was compared using analysis of variance with post-hoc Tukey's honestly significant difference test. A p-value of less than 0.05 was taken as significant. 3% mannitol + psyllium achieved superior mean luminal distension in the ileum (2.28 cm, 95% confidence interval [CI] 2.25–2.31) compared with 3% mannitol alone (2.12 cm, 95% CI 2.08–2.16), 2% mannitol (1.49 cm, 95% CI 1.46–1.52), 1% mannitol (1.30 cm, 95% CI 1.26–1.34), and water (0.67 cm, 95% CI 0.63–0.71) (p < 0.001). Similar trends were observed for the jejunum and terminal ileum (p < 0.001). Fold visibility and contrast homogeneity were significantly better with 3% mannitol + psyllium (p < 0.001). Diarrhea was most frequent with 3% mannitol alone (48%) and 3% mannitol + post-CT water (44%), but reduced to 28% with 3% mannitol + psyllium (p = 0.02). No severe adverse events were reported except for diarrhea, a feeling of fullness, nausea, vomiting, headache, and others with increasing concentration of mannitol. 3% mannitol with psyllium provides optimal bowel distension and mucosal visualization in CTE with improved tolerability compared with mannitol alone. This combination represents an effective and patient-friendly preparation for routine clinical use in small bowel imaging. Our study is the first to demonstrate the synergistic benefit of mannitol and psyllium in achieving optimal small bowel distension with reduced adverse effects in a randomized double-blind design with extended adverse event monitoring. Clinical Trials Registry of India (CTRI/2024/02/063015)